This is an intermediate level course. After taking this course, mental health professionals will be able to:
PART I: Underlying Causes
PART II: 8 Important Areas of Evaluation
“A number of those who are exposed to stressful life events become ill, but most do not. Conversely, it is possible to fall ill despite living a life of unruffled stability.”
Paul Martin, Ph.D. The Healing Mind
Since the dawn of civilization, mental illness has fascinated us. In ancient times, unusual and bizarre behaviors were thought to be caused by gods. Other societies believed that these behaviors were due to possession by incubi and demons.
More recent theories included organ malfunction, such as the belief that hysteria was caused by a wandering uterus. Others touted Hippocrates’ imbalance of humors. More recent theories have included suppressed memory, trauma, poor parenting, and refrigerator mothers. The most wildly held belief of mental maladies today is that they are a manifestation of unruly neurotransmitters.
For the last several decades, the field of mental health has been dominated by two major paradigms: psychotherapy and psychotropics.
Up until a century ago, mental illnesses were diagnosed and treated by medical doctors. It wasn’t until about 1948 when the specialty of neuropsychiatry was divided into two fields: neurology (which dealt with physical diseases of the brain) and psychiatry (which focused on emotional and behavioral problems). Soon afterward, psychotherapy delivered by non-medical professionals began to be considered a valid way to treat mental disorders.
Medical illnesses can cause people to experience a baffling array of emotional, cognitive, and behavioral problems. People suffering from these problems are usually unaware of their maladies. If there are accompanying medical problems (e.g., diabetes, cardiovascular disease), they may exhibit a poor response to therapy and/or psychotropic medication. In addition, psychological reactions to known medical problems can complicate medical management and treatment.
Whenever a patient presents a psychological problem, there is a very real possibility that an underlying medical condition may be a factor – either as an outcome of the psychological condition or as the original cause. Understanding the role that biological processes play in that disorder can often help you recognize telltale signs of medical causes of behavioral, cognitive, and emotional disturbances.
Although most patients will not have a causative underlying medical condition, the growing impact of environmental toxins, drug interactions, and degenerative diseases have increased the possibility that there is a medical origin for the condition.
While psychotherapists should not live in fear of missing an unsuspected medical origin, it is important to have adequate knowledge of the medical issues that could potentially relate to their patients' conditions. This course will provide an overview and source of reference to help make a basic assessment to determine whether medical consultation might add insight to a case. Naturally, it is not intended to provide psychotherapists with the tools needed to diagnose these medical conditions. It will, however, lay the groundwork to allow a therapist to speak in a knowledgeable way with consulting physicians and improve the likelihood of a good evaluation for the patient.
Although not every mental health problem is masking a primary medical condition, one thing is certain – when there is an underlying medical component, psychotherapists who do not consider the possibility are certain to miss the diagnosis.
“Many mental hospitals are living museums of undiscovered bodily disease.”
FMR Walshe, MD
“The more that is understood about how the human mind processes complex information, the more it becomes clear that certain situations are particularly susceptible to less than optimal outcomes because of these errors.”
Antoinette Laskey, M.D., M.P.H.
Consider this scenario: A family comes to a psychotherapist for help because the middle child has been defiant and difficult. He refuses to go to bed at night. During the day, he is hyper-reactive and non-compliant. This often leads to family squabbles, which frequently morph into arguments between the parents. As the therapist works with the family, it becomes clear that the fights are exacerbated by the husband's angry outbursts and bouts of rage. Although the family works hard to improve its coping skills, communication, and problem-solving abilities, the conflicts persist.
It is a baffling situation. Neither the therapist nor the family members are aware that the father, who lives on a diet of fast food, has developed extremely low levels of omega 3 fatty acids. This medical condition, not his emotional profile, is the root cause of his anger and rage. Without a physical and lab testing, this problem will likely not be detected.
Although many psychotherapists are aware of the possibility that underlying physical conditions can cause or exacerbate emotional issues, the reality is that a majority of mental health practitioners spend most of their time treating uncomfortable feelings or social problems – not mental disorders, much less medical problems. As a result, they can easily miss the signs that might lead them to recommend a professional medical diagnosis.
Even internists and physicians at hospitals often miss the underlying medical causes of mental and emotional issues. Despite advances in medical technology, there is still no test to definitively identify mental disorders. At best, medical evaluations can provide clues and help eliminate some of the variables. When the patient's symptoms do not correspond precisely to the reference books or to similar cases they have personally encountered in the past, a physician may make a misdiagnosis as easily as a psychotherapist might.
The challenge of finding potential underlying medical causes is complex. This makes failure to recognize and diagnose an underlying condition in a patient a reasonably common occurrence.
“The reliance on patient self-report of symptom severity, and on the clinicians' impression, is a rate-limiting step in effective treatment.”
Helen Le-Niculescu, Ph.D.
“We intend to forget the richness of our ignorance – how much we don’t know and how essentially we learned what we do now.“
Dan Agin Ph.D. Biological Psychology
For most psychotherapists, a good proportion of clients come for help in coping with the problems of life. These may include unwanted moods, uncomfortable thoughts, personal problems, relationship problems, and/or family strife.
Outpatient psychotherapy, couples therapy, and family therapy are some of the many techniques designed to address these woes. Family therapists routinely work with quarreling couples and troubled children amid what are often called dysfunctional families. While psychologists and other mental health professionals in private practice also address family dynamics, they are more likely to spend time working with personal or phase-of-life difficulties, as well as treating symptoms of depression, anxiety, and panic attacks.
There is no doubt that many family therapies and psychotherapies can be useful and effective in ameliorating these problems. Family therapy, couples therapy, group therapy, cognitive behavioral therapy, and other techniques have been shown to be quite effective in attenuating mood disorders, relationship problems, and social quandaries.
Although people may leave therapy feeling better, problems often recur. Even couples or families who leave your office thanking you profusely may reappear at your door six months later. People with chronic depression inevitably relapse. These events suggest that, beneath a presenting problem, may lay an undetected, chronic pathology that is the root cause of their woes. Most psychotherapists are not medical doctors, research scientists, or geneticists. Nevertheless, all mental health professionals today must have a working knowledge of how the body works and how the world we live in affects brain function.
In the last few years, incredible developments in neuroscience, genetics, epigenetics, physiology, pharmacology, the immune system, toxicology, and nutrition indicate that many mental problems can be caused, exacerbated, and treated by alterations in biological and biochemical processes.
“I’ll see it when I believe it.”
Thane Pittman, Ph.D.
Psychotherapists are taught how to diagnose mental disorders and deliver psychotherapy. To diagnose means to observe, identify, and determine the cause of a disease or disorder. To make a differential diagnosis means to distinguish between disorders with similar presentations by comparing their signs and symptoms.
The diagnosis of a mental disorder is most often done by observing signs and symptoms which fit the diagnostic criteria in the Diagnostic and Statistical Manual (DSM). Practitioners also use tests and assessments as diagnostics tools. Although these techniques have value, they seldom address the cause of the mental disorder.
In his book, A Dose of Sanity, psychiatrist Sydney Walker points out that “a label is not a diagnosis.”
DSM-5 has included a category named the neurocognitive disorder, which was formally known in DSM-IV as 'dementia, delirium, amnestic, and other cognitive disorders.'
We know what dementia, depression, and cognitive disorder look like, but we often do not know what causes them. We use words like reactive depression, endogenous depression, or organic mental disorders, but few professionals actually understand the implications of these terms.
The truth is that many medical disorders manifest themselves by psychological symptoms and organic mental disorders are not distinguishable on the basis of mental and emotional symptoms.
An initial evaluation usually begins with an interview about the person’s major complaint. When people come to us for help, they describe their problems. As they are doing so, we listen carefully for signs and symptoms. For example, if Mr. Johnson tells us he is not sleeping well, has aches and pains all over his body, has lost his appetite, and is feeling hopeless, we begin to think he may be depressed. If he tells us that he has racing thoughts and difficulty sleeping, we begin to think he may have bipolar disorder. This strategy is useful, but often inaccurate.
Once we begin to feel confident that we have the diagnosis, we get a history of Mr. Johnson. We want to know about his childhood, his family, his hopes, and his fears. We are looking for pieces of his history that fit our theory. When he tells us that his father repeatedly abused him, we feel we know something about the cause of his problems. Oftentimes, we do not question the veracity of what we are told and have no solid data other than his subjective account to indicate that this may be the cause of his woes, but since the story does fit our belief system, it bolsters our confidence.
All mental health professionals are trained in certain theories of diagnosis and treatment. They come to believe, for example, that depression is caused by faulty thinking, is caused by lack of serotonin, or is caused by repressed trauma or abuse.
One of the pitfalls of effective psychological intervention is theoretical bias. All of us have specific training, received from professors who had their own pet theories of psychopathology. Although being trained in a certain type of psychotherapy has value, it also can lead a clinician to overlook any signs and symptoms that do not coincide with her belief system.
I was struck by this many years ago while in graduate school. One on my professors – who was trained in classic psychoanalysis – recounted the case of a woman in her mid-thirties who could not decide if she wanted children. Although her husband was clear about wanting a child, she was ambivalent and worried that she would be an inadequate mother.
The professor’s theory was that his patient had some deep, repressed ambivalence about her own mother. He felt confident that, once these feelings came to light, the patient's indecision would disappear. He told us that, after four years of psychoanalytic therapy, she had still been unable to make the decision. Unfortunately, in this case, the problem was not well-suited for psychoanalysis. As the years rolled by and the patient became older, the problem would gradually become moot.
Pet theories come and go. Some have value, some are fads, and some are simply bizarre. In 1987, author Whitley Strieber wrote Communion, an allegedly non-fiction book describing his encounter with aliens whom he claimed had abducted and sexually molested him. After reading his book, dozens of people flocked to the fast-growing group of alien abduction therapists. John Mack, a well-known psychiatrist and Harvard professor, set the diagnostic criteria for alien abduction syndrome, which included nightmares, sleep paralysis, bruises, phobias, unexplained scars, and fear of the dark.
During this period, there was another spate of unusual encounters – an upsurge in cases of people allegedly suffering from years of satanic ritual abuse, which purportedly resulted in post-traumatic stress syndrome and multiple personality disorders. At the time, I was on the treatment staff of three psychiatric hospitals. Each of these hospitals had opened a special unit for people who had been satanically abused. All subsequently developed multiple personality disorder.
I listened carefully to the experts at the hospital as they explained the origin of these pathologies. However, I begin to be skeptical as I saw people coming in with a variety of mental disorders, all of which were declared to be caused by satanic abuse.
In one hospital, treatment protocols dictated that all patients attend group therapy. During group therapy, they were encouraged to remember and disclose their satanic abuse and to share their multiple personalities. If these memories and personalities had not emerged prior to admission, the patients were encouraged to manifest them through the technique of sodium amytal regression. None of the people in this hospital was considered to be a member of the group until they’d had “their sodium.”
I was astonished by how malleable people can be. With their high level of anxiety and need to fit in, it was easy to convince these patients that they had been abducted by aliens or satanically abused.
Many patients left the hospital with much more severe pathology than they had had when they went in. This prompted me to become skeptical about how diagnoses were made, and resulted in my writing the book, The Abduction Enigma: The Truth Behind the Mass Alien Abductions of the Late Twentieth Century. (As my co-author Kevin Randal pointed out, there is also a culture-bound bias in the diagnosis of these alleged maladies. There are few African-Americans, Hispanics, or Asians in the satanic abuse, or multiple personality population.)
One of the unexpected events that followed the release of this book was the anger and outrage it spawned. I received a large volume of hate mail, filled with threats and animosity, from psychotherapists. Rather than disagreement or discourse, these mental health professionals were protective of their favored theories and outraged that anyone should disagree with their belief systems. This level of bias is unfortunately common enough that it is one of the primary reasons people do not receive objective diagnoses and effective treatments. By the way, since 1987 it seems that the number of abductions has declined significantly.
Webster’s Medical Dictionary describes psychotherapy as, “The treatment of a behavior disorder, mental illness, or any other condition by psychological means. Psychotherapy may utilize insight, persuasion, suggestion, reassurance, and instruction so that patients may see themselves and their problems more realistically and have the desire to cope effectively with them.”
Therapy has helped thousands of people. If you are in private practice, you know that many of your clients are grateful for the help you have given them. However, you also are aware that some of your clients did not get significantly better. At times, when people do not improve with treatment, we label them treatment resistant.
Couples therapy and family therapy are useful in increasing the quality of family life. However, many mental health practitioners, marriage and family therapists are not taught to screen their families for medical illnesses. As a result, one or more family members with a medical illness may display behaviors that are significantly disrupting to the family dynamic. Research on couples and family difficulties are often spawned by abnormalities in the immune system of one or more family members. Problem solving and empathy training will not fix these problems.
When a mental illness is involved, we may send the person to a physician for a prescription of psychotropic medication. This sometimes helps, but sometimes does not. In that event, rather than labeling the outcome treatment failure or treatment resistance, it is often more accurate to recognize the problem as the wrong diagnosis. It may well be that the outbursts of anger Mr. Johnson exhibits will not remit until the malfunction of his adrenal glands is addressed.
Ironically, even if overstressed adrenal glands must now be managed before Mr. Johnson can resolve his marital problems, the marital problems may have contributed to his existing condition. Stress hormones are higher in the conflicted couple even when they aren't arguing, and it represents a chronic pattern of stress in the marriages.
The quality of a marriage is a strong predictor of physical health. A study by Janice Kiecolt-Glaser and her colleagues looked at the levels of norepinephrine in the blood of married couples and then assessed each couple’s marital status ten years later. They found that couples who had divorced by ten years had already displayed a 34 percent higher rate of norepinephrine at the beginning of the study than couples who stayed married.
Distressed marriages can cause effects on the immune system. These findings suggest that personal relationships become translated into health outcomes. The research also suggests that couples with high levels of conflict are more likely to present with physical illnesses.
“A lot of what passes for depression these days is nothing more than a body saying that it needs work.”
The diagnosis of a mental disorder must include an evaluation of the patient’s physical condition. It is essential to avoid missing an underlying medical disorder. Mental health providers should always ensure that the physical health of the patient has been thoroughly evaluated before psychotherapy has commenced.
The brain is a component of the body. It interacts with every organ, system, and tissue. When the body is not working properly, it impacts the brain. Therefore, a mind that is not working properly is often a sign of a malfunction of the body.
“Mental health and physical health are intertwined; both types of care should be provided and linked together within health care delivery systems.”
Craig W. Colton, PhD and Ronald W. Manderscheid, PhD. Johns Hopkins
It has been known for decades that people with mental disorders die earlier that the average population. In the last few decades, the mortality rate has increased. In the 1990s, the mentally ill died 10-15 years earlier than mentally healthy adults. By 2006, however, the shortened life expectancy was 25 years.
Many of these early mortalities are thought to be the result of the change in medications. Second generation antipsychotic medications have become more highly associated with weight gain, diabetes, dyslipidemia, insulin resistance, and metabolic syndrome. But while many researchers believe that the high mortality rate in mental disorders is caused by the psychoactive drugs given, others believe that the early demise is because of unknown physical disorders that were not looked for, detected, or treated.
Psychotherapy seldom begins with a complete physical. Yet research suggests that about half of all psychiatric patients have an undetected physical illness. This illness may or may not be the cause of the mental symptoms, but it must be taken into consideration.
Research suggests that about 80 percent of physical illnesses are missed during initial mental health assessments. Most often this occurs because the clinician has not spent time taking a thorough medical history. The danger here is that many people with emotional, mood, or thought disorders tend to seek out mental health services before they consider a medical assessment. It is not until they get worse or develop observable physical illness that they seek medical help. Unfortunately, by this time the disease has progressed to a serious level.
“The medical profession is unconsciously irritated by lay knowledge.”
Recognizing a medical problem that is contributing to a mental illness is difficult, but there are certain red flags that suggest physical causes. After the initial question, "How can I help?" keep these factors in mind:
When a person does not respond to well-known treatments for a disorder, the most likely explanation is that they do not have the disorder. There is no known illness that is "treatment resistant." Rather than blame the victim, seek another diagnosis, and if needed, seek another treatment. Efficacy studies suggest that about one-half of people with psychological problems will benefit from psychotherapies, psychotropics, or both.
“There are lots of kids with behavior problems who may outgrow them on their own without medication, versus the minority with mental illnesses that need treatment. Family history is the quickest and cheapest way to sort that out.”
Rick Nauert PhD.
Most people are aware that their curly hair came from their grandfather and their big ears came from their mom, but they seldom see their dark moods, pessimism, and short tempers as traits handed down from their Uncle Phil. In fact, most mental illnesses do run in families, which suggest that they have a genetic and/or perhaps environmental component. Many families have long histories of mental problems, or medical disorders known to contribute to mental problems. For this reason, an intake interview should always include a personal and familial history of medical and mental illnesses. The absence of mental illness in a family is a signal that the malady in this person has a higher probability of being caused or exacerbated by a physical ailment.
Roughly half of all lifetime mental disorders start by the mid-teens and three-quarters by the mid-twenties. Those who develop mental disorders for the first time in late life are more likely to have medical conditions that contribute to or cause their problems. Significant changes occur with normal aging. Body mass, hormones, nutrient absorption, and vascular changes have profound impacts on brain function. For example, people over fifty are more prone to depression caused by nutritional, arthritis, cardiovascular, and endocrine disorders.
Most mental disorders develop slowly and get worse with time. Therefore, the sudden onset of a mental disorder is a red flag for biological abnormalities such as vascular disease, strokes, nutritional deficits, infections, hormone irregularities, tumors, or exposure to toxins.
Although many mental disorders may fluctuate over time, volatility of symptoms is unusual. Fluctuation of mental status often indicates a dementia, delirium, or metabolic disarray. Delirium can be caused by many medical disorders, particularly infections and inflammation. Bladder infections may have no overt symptoms other than delirium and may go undetected for months. Exposure to toxins may also present with waxing-and-waning mental symptoms.
As discussed earlier, most mental disorders are diagnosed by their symptoms. For this reason, when a person displays classic symptoms of a mental illness, but also has symptoms that do not fit the criteria, medical problems should be considered.
People who work swing or night shifts tend to have more emotional problems. They often have a constant sleep deficit which makes them prone to mood disorders and problems with memory and/or concentration. Sleep disorders, such as apnea, may go undetected for years or be misdiagnosed as attention deficit disorder or depression.
Nutrition plays a significant part in all mental illnesses. A thorough dietary history is essential. Eating patterns also play a part in mood and behavior. For example, children who do not eat breakfast are more likely to be diagnosed with attention deficit hyperactivity disorder. Get a thorough list of favorite foods, favorite brand name foods, and favorite beverages. Also, document any and all known food allergies or sensitivities.
Be cognizant of any abnormalities in the motor system. This includes tics; disturbances of gait and balance; clumsiness; and problems with speech, language, or enunciation. All of these suggest problems in the motor system. These can be signs of Tourette’s Disorder, basal ganglia problems, or motor-neuron disturbances, all of which can present as mental disorders.
Undisclosed substance abuse may be the cause of the symptoms you observe. In many cases, the person using these substances will not disclose or admit substance abuse, which makes any diagnosis invalid or suspect. Others do not see the connection between the use of the substance and their problems. Others simply do not want to stop using it and, therefore, are reluctant to disclose the use of the substance.
Stopping a medication, changing medications, and experiencing interactive effects of medications can change mental status. In addition, as people age, medications may be metabolized differently. A medication they have been taking for many years may begin to cause problems. This is true not only of prescription medications, but also over-the-counter remedies.
Polypharmacy has become a significant factor in mental health, particularly in elderly adults. The world of nutritional supplements is exploding. It is likely that some of the people you see will be taking multiple supplements, such as vitamins, minerals, amino acids, herbal extracts and neuroactive fats, such as omega 3. Any one of these substances can cause metabolic changes. They may also interact with medications. Always ask about ointments, creams, cosmetics, hairsprays, and other chemicals in their environment.
“Mental disorders are not rare among travelers”
World Health Organization
Travel, especially travel out of the country, can also cause exposure to unfamiliar toxins, parasites, and infections which may present as emotional, cognitive, and behavior disorders. Asking about recent moves, home remodeling, and travel is essential. Moving is stressful. This experience alone can cause enough stress to destabilize a mind. Moreover, the new home or the neighborhood may also contain toxins and environmental loads that contribute to mental problems. Remodeling usually means exposure to paints, carpets, adhesives and other chemicals which can cause mental problems.
Unfortunately, neurotoxicity is becoming a major contributor to both physical and mental illnesses. The high levels of contaminants in our environments can no longer be ignored. It is important to ask the person’s vocation. Does their job expose them to toxins? At home, do they use insecticides, herbicides, fertilizers, or room deodorizers? Does your client have pets? Are the pets using flea sprays or other medications? Families who work in the agriculture industry have a high incidence of depression, anxiety, and sleep disorders often caused or exacerbated by pesticide exposure.
Although asking a person how much money they make may be inappropriate, socioeconomic status is a useful piece of diagnostic information. In general, low socioeconomic status increases the risk of psychological disorders. In fact, one of the most consistently replicated findings in social science research is the negative relationship of socioeconomic status with mental illness. Less income may result in living in a neighborhood which has higher crime rates and higher levels of toxins. It may dictate which groceries are purchased. It may also give you information about the person’s values, belief systems, and coping skills.
Get a thorough history of visits to doctors and mental health clinicians. What were the outcomes? Has there been a recent physical? A thorough physical is an essential part of diagnosing and treating any mental disorder. The difficulty here is that there are hundreds of maladies and metabolic anomalies that can cause mental problems. A general physical cannot assess all maladies. Unless a person is suffering from a common physical illness, it is not unusual that the correct medical diagnosis will be missed over a span of several years. In fact, the reason for the person’s visit to you may be because physicians have failed to find a biological cause of the presenting problem and, therefore, have labeled the malady a mental disorder.
A neurological exam is useful, but rarely done unless a person has significantly unusual behaviors. Conditions that involve subcortical regions of the temporal lobe are commonly associated with delusions, unusual sexual behavior, and paranoia, but a routine physical will not include tests such as an EEG or brain scan.
Abnormal lab results may suggest a medical cause of a mental symptom, but keep in mind that lab levels are norms, not people. Problems such as B12 deficiency and thyroid problems often occur even when labs come back normal and are, therefore, frequently diagnosed as mental illness. Subclinical abnormalities of calcium or magnesium may not reach levels that would be diagnosable as abnormal, but may cause significant problems in the central nervous system.
Religion and spirituality play a significant part in mental health. They shape a person’s belief system diet, and lifestyle. Research shows that religiosity is correlated with brain structure. Research also shows that, in general, people with well-developed religious beliefs tend to be healthier than those who are not, while hyper-religiosity is sometimes tied to mental problems, particularly seizures, depression, mania, paranoia, and psychosis.
Always ask if your client is or has ever been a smoker. Smoking has long been linked to depression. It has been found that depressed teens are more than twice as likely to become moderate to heavy smokers. Teens that are not depressed, but become heavy smokers, are four times more likely to become depressed later in life.
Nicotine also affects the locus coeruleus, located in the brain stem which regulates brain regions responsible for emotion and mood. Researchers believe that it is the nicotine in tobacco that mimics the effects of drugs that produce antidepressant effects. Long-time smokers have approximately 60 percent lower levels of the protein tyrosine hydroxylase and 40 percent lower counts of alpha2-adrenoceptors in the brain. Tyrosine hydroxylase helps to manufacture noradrenaline and dopamine.
Bupropion (marketed as Wellbutrin® and Zyban®) is an antidepressant that also helps smoking cessation. It acts as a norepinephrine and dopamine reuptake inhibitor and nicotinic antagonist. (Be aware that Bupropion is known to cause seizures.)
There is also evidence that smoking can damage the thyroid, causing or worsening thyroid problems.
Tobacco smoke contains cyanide, which in the body is converted to thiocyanate, which then acts as an anti-thyroid agent, directly inhibiting iodide uptake, interfering with hormone synthesis.
You should also ask if their mother smoked during her pregnancy. There is also evidence that maternal smoking can affect the fetal brain. Smoking during pregnancy is correlated with low birth weight, but it is also associated with low scholastic achievement, conduct disorder, and attention deficit hyperactivity disorder. In addition, maternal smoking during pregnancy is also associated with earlier age of offspring initiation of smoking and onset of regular smoking.
Since so many medical illnesses manifest themselves as mental illnesses, a thorough medical history is essential. If your client has known medical conditions at the time you see her, start there. Explore the known psychological symptoms that accompany this disorder. Unfortunately, a comprehensive physical exam is seldom done. Psychotherapy and psychotropics are less expensive. The technical term for the presence of a mental disorder and medical disorder occurring together is comorbidity. What is missed is that, at times, the medical problem is the major cause of the mental disorder. For example, comorbidity is common in anxiety and depressive disorders, particularly in cardiovascular disease, skin problems, and diabetes.
“The main risk factors identified for developing depressive disorders were: being female, over 40 years old and being married.”
Hernández-Benítez CT, García-Rodríguez A, Leal-Ugarte E, Peralta-Leal V, Durán-González J.
Many medical conditions – including heart disease, breast cancer, prostate cancer, diabetes, alcoholism and Alzheimer's disease – have been shown to be passed down through families. Physical illnesses or vulnerability for illnesses runs in families. These illness patterns can be caused by genetics, but also are related to idiosyncratic family diets, lifestyles, exposure to toxins, geographic location, and socio-economic status.
Look for early family deaths. People with mental illness tend to die young, but so do their families. A prime example of a familial pattern of mental illness is the connection between heart disease and depression in families (which is presented below). Relatives of people with early-onset major depression die younger than the normal population – an average of eight years younger than normal life expectancy. More than 40 percent of first-degree relatives die before reaching age 65. There is also a five-fold increase in infant mortality rates. Older family members have a greater than average incidence of Alzheimer's.
Is there a significant level of osteoporosis in the family? Major depression commonly co-occurs with decreased bone mineral density.
Family history, family medical records, death certificates, obituaries, and old family letters can be valuable sources for medical histories. Even old family photos can sometimes provide visual clues to diseases such as obesity, osteoporosis, and hair or skin problems. A thorough medical history can also give you data about family genetics and genetic fallout.
bone connected to your shoulder bone. Your shoulder bone connected to your neck bone.
Your neck bone connected to your head bone. I hear the word of the Lord.”
Dem Dry Bones
“See, I told you I was sick!”
Somatic Symptom and Related Disorders
|Signs of somatic disorders||
Visual nerve injury
Constipation, loose bowels, or diarrhea
|Nausea, gas, or indigestion||Multiple sclerosis|
|Back pain||Hearing loss|
|Chest pain||Cerebrovascular disease|
|Pain in arms, legs, or joints||Fluid or electrolyte imbalances|
|Menstrual cramps||Huntington's chorea|
|Pain during sexual intercourse||
Heart pounds or races
|Shortness of breath|
The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), changed the term “somatoform disorders” to “somatic symptom and related disorders” and further modified diagnostic labels and criteria.Somatic symptom and related disorders are defined as “persistent physical symptoms that cannot be fully explained by a medical condition, substance abuse, or other mental disorder, and seem to stem from psychological issues or conflicts.” These disorders are believed to be quite common. Studies of healthcare utilization estimate that 25-72 percent of office visits to primary care doctors involve psychological distress that takes the form of somatic (physical) symptoms. Another study estimates that at least 10 percent of all medical treatments and diagnostic services are ordered for patients with no evidence of organic disease.
The problem in this category of diagnoses is that there is no scientific evidence that this can occur. In other words, to date, there is no known physical mechanism by which emotional difficulties can be “somatized.” Researcher Oliver Oyama suggests, “These disorders should be considered early in the evaluation of patients with unexplained symptoms to prevent unnecessary interventions and testing.”
The problem here is two-fold. As long as we label unusual maladies as psychosomatic of somatoform, we risk missing an underlying illness. Although tests can rule out specific maladies, there is no medical assessment that can diagnose the absence of illness.
In his book, How Doctor’s Think, physician and Harvard professor Jerome Groopman states that most doctors begin to make a diagnosis in the first few minutes of their assessment. Once this process begins, the doctor may dismiss symptoms that do not fit his preliminary diagnosis.
Groopman states: “Clinical algorithms can be useful for run-of-the-mill diagnosis and treatment – distinguishing strep throat from viral pharyngitis, for example. But they quickly fall apart when a doctor needs to think outside their boxes, when symptoms are vague, or multiple and confusing, or when test results are inexact. In such cases – the kinds of cases where we most need a discerning doctor – algorithms discourage physicians from thinking independently and creatively. Instead of expanding a doctor's thinking, they can constrain it.”
Groopman also confesses in the beginning of his book that he has no idea how mental health practitioners make a diagnosis, because there is often complete absence of an observable physical abnormality to verify the pathology.
One-third of new referrals to neurology clinics have symptoms that are poorly explained by identifiable organic disease. It is not uncommon for a person who has an array of symptoms that do not fit any particular disease criteria to be labeled as having somatization disorder. The patient will then go doctor shopping, which will eventually get them the label of hypochondria. Oftentimes, the sufferer will eventually find a doctor who actually finds the undetected medical disorder, or the person will become so ill that it becomes clear that a medical disorder is the cause. Diseases such as Lupus, multiple sclerosis, Lyme disease, parasites, or intestinal infections are often misdiagnosed as mental illness. (All of these are discussed below.)
“The conversion symptom is a code that conceals the message from the sender as well as from the receiver.”
Marc H. Hollender, MD
“This causal link between psychologic events and physiologic changes may be much more complex than we have been led to believe. Or this assumed causal link may not exist at all: Concomitant events are not necessarily causally related.”
Herbert Weiner, MD Presidential Address, American Psychosomatic Society, 1972
Medical conditions diagnosed as conversion disorders
The DSM-IV-TR classifies conversion disorder as one of the somatoform disorders which were first classified as a group of mental disorders in 1980 in the DSM III.
The new description of somatic symptom disorder in DSM-5 represents a big step forward, because the decision has been made to use, for classification, a positive criterion, namely maladaptive reaction to a somatic symptom, instead of the earlier negative criterion.
The primary cause of conversion disorder is purportedly a traumatic event or stressful situation that leads the patient to develop bodily symptoms as symbolic expressions of a preexisting psychological conflict. Many mental health practitioners believe that physical, emotional, and/or sexual abuse is a contributing cause of conversion disorder in both adults and children. In fact, these events are often correlated, but keep in mind that correlation is not cause-and-effect.
A study of 34 children who developed pseudo-seizures showed that 32 percent of the children had a history of depression or sexual abuse, and 44 percent had recently experienced a parental divorce, death, or violent quarrel. But familial studies have also shown that conversion symptoms in first-degree female relatives are up to 14 times greater than in the general population, suggesting a genetic predisposition to these symptoms.
Conversion disorder is also thought to develop in adults as a “long-delayed after-effect of childhood abuse.” One team of surgeons reported a case of a person who went into a psychogenic coma following a throat operation. The surgeons found that she had been repeatedly raped as a child by her father, who stifled her cries by smothering her with a pillow.
In the adult population, conversion disorder may be associated with mobbing, a term that originated among European psychiatrists and industrial psychologists to describe psychological abuse in the workplace. One American woman who quit her job because of mobbing was unable to walk for several months. Adult males sometimes develop conversion disorder during military basic training.
One problem with this diagnosis is that conversion disorders seem to be culture bound. Mental health practitioners in the Middle East and Asia have reported that symptoms of conversion disorder in the DSM-5 and ICD-10 do not fit with the symptoms of the disorder most frequently encountered in their populations.
Most conversion symptoms afflict the left half of the body. Researchers hypothesize that a dysfunction in the right amygdala and parietal lobe circuits are the cause of the disorder. Brain damage in these areas often causes conversion symptoms and body image distortions. Some studies suggest that changes in these areas could be caused by traumatic events, which result in changes in body image, perception, and behavior.
Unfortunately, there is no way to prove that a conversion disorder is caused by psychogenic trauma. Before this diagnosis is rendered, clinicians should make sure the client has had a complete medical workup. Conversion disorders may be signs of hypoglycemia, an undetected neurological disorder, or a seizure disorder. Researcher Iraj Derakhshan found in 79 consecutive patients with conversion disorder, 76 percent had unilateral cerebral abnormalities found in brain scans, while abnormalities on EEG assessments were found in 78 percent.
“Psychological and social stressors are a recent element which we have learned often provoke our bodies into an accompanying uproar linked to mere thought.”
Robert Sapolosky, 1994
Symptoms of Hypochondria
Lifetime history of anxiety
Multiple system somatic symptoms
Unusual array of symptoms
Atypical response or poor response to treatment
|Non-compliance with treatment|
|Absence of concern about symptoms|
|Symptoms exacerbated by certain situations|
Apparent secondary gain
Hypochondria is the interpretation of bodily symptoms as signs of a serious illness. Frequently the symptoms are normal bodily functions, such as coughing, pain, sores, or sweating.
Although some people will be aware that their concerns are excessive, many become preoccupied by the symptoms. Typically, this will trigger frequent visits to doctors.
They often are preoccupied with the belief that they have a serious illness, and have a penchant for bodily functions. They often ruminate about illnesses, have an unrealistic fear of infection, and have a fascination with medical information. They may spend a great deal of time on the Internet looking at diseases, symptoms, and treatments.
Hypochondria is classified as an anxiety disorder. There is little doubt that hypochondria is a viable diagnosis. However, it is also clear that many people given this diagnoses actually suffer from an undetected medical condition. For example, Lyme disease is often misdiagnosed as hypochondria.
In many cases, a family history will reveal that many family members suffer from similar maladies. Charles Darwin and five of his seven children were diagnosed as suffering from either hypochondria or depression. It appears that the man who created the theory of natural selection and inherited traits may have had a familial genetic predisposition for mental illness.
”An evolutionary perspective is not part of the thinking repertoire of a psychiatrist when faced with a mentally ill patient."
Hagop S. Akiskal, MD
The world of gene testing is exploding. Today, there are dozens of companies that can detect genetic predispositions to illness. As a result, new treatments are emerging which can alter gene expression. This is the world of genomics. All health practitioners need to have a working knowledge of this breakthrough.
The mapping of the human genome has revealed a multitude of genes which are highly correlated with the presence of mental illnesses. The rapid development of genetic testing can reveal a person’s vulnerability to mental disorders.
DNA is a series of molecules linked together in a microscopic spiral called a chromosome. Humans have 23 chromosomes, and every cell in our body has two versions of each of the 23 chromosomes – one from each parent. This combination is called a diploid genome.
The human genome contains a total of 30,000 genes. Females have two X chromosomes, while males have one X and one Y chromosome. We inherit half of our genetic profile from each parent. Both males and females retain one of their mother's X chromosomes, but females retain their second X chromosome from their father. Since the father retains his X chromosome from his mother, human females have one X chromosome from their paternal grandmother and one X chromosome from their mother.
It is for this reason that many of us resemble our parents, not only in appearance, but in personality, demeanor, social skills, and coping skills. In addition, we also may inherit genes that can cause or increase the risk of medical disorders.
The interplay between fraternal and maternal genes has consequences for mental illnesses as well. It has long been established that most people with mental disorders have a genetic predisposition to their woes. We know this because mental disorders run in families. However, it is now evident that the predispositions to certain medical disorders are predictors of mental disorders in family members, and that family genetics contribute to mood, behavior, and mental well-being.
Recent breakthroughs in genetic testing have made it possible to plot a person’s paternal and maternal genes – and their contributions to diseases – separately. These discoveries have revealed that a fundamental cause of many human maladies is how these two sets of genes interact.
Ninety-nine percent of all human DNA is identical, but that one-percent difference is often the root cause of mental disorders. The complete mapping the human genome has allowed researchers to scan DNA for genes that may cause, contribute to, or even prevent mental disorders.
At the time of this writing, despite the explosion of genetic research, only a small number of these genes have been identified. But even though gene research in mental illness is still in its infancy, a person can still gather some information about their genetic risk of physical and mental illness simply by looking at his family tree. Moreover, looking at the family history of certain maladies can predict other problems in family members. The old Talmudic adage “fruit falls near the tree” is genetically true. These familial problems can be said to be family fallout.
“Genetic inheritance is merely the template upon which we build our unique life experience.”
Jeffery Bland, Ph.D.
It has long been known that mental problems run in families. What is not well known is that the children and relatives of people who have mental or medical illnesses are also prone to other illnesses. The people you work with will tell you about their mental symptoms, but they will seldom disclose their physical maladies. Furthermore, without prompting, they will not discuss the medical problems of their family. Knowing a family‘s medical and genetic history can reveal the roots of pathology in a client.
Genetic penetrance is the likelihood that a certain gene will result in a specific disease. In 2006, researcher Roger Webb, at the University of Manchester in England, showed that the risk of fatal birth defects is higher in the children of parents who have been hospitalized for mood disorders. There is even more risk is associated with maternal schizophrenia. Moreover, children of mothers who had previously been admitted to a hospital for any type of psychiatric diagnosis had significantly higher risk of death from birth through early adulthood. In addition, the relative risks associated with the mother’s illness varied significantly by the child’s age and were generally greatest in the first year of life, during the neonatal (early and late) and post-neonatal periods. The risk of infant death among children with two mentally ill parents was significantly higher than that associated with having only one affected parent. Families with fathers or mothers who have a history of psychiatric hospitalizations also double the risk of sudden infant death syndrome (SIDS) compared with the general population. If both parents were hospitalized, the risk of SIDS was increased by almost seven-fold. There is evidence that SIDS may be in part caused by abnormalities of serotonin in the brainstem.
“Beneath the emotional surface of mood and depression can be a raging physical undercurrent of hormonal distortions, impaired immunity, and inflammation.”
William Davis, MD, FACC
There is strong evidence of a genetic transmission of recurrent major depression. In fact, having a family member with major depression increases a person's risk eight-fold. Heritability is considered to be about 30-40 percent. A history of depression in a parent is the strongest risk factor for depression in a child.
Researcher Myrna Weissman at New York State Psychiatric Institute found high rates of psychiatric disorders – particularly anxiety disorders – in the grandchildren of families with two generations of major depression. Fifty-nine percent of these grandchildren, with a mean age of twelve years, were suffering from a psychiatric disorder. A twin study found a 46 percent concordance of depression in identical twins and 20 percent in fraternal twins. Interestingly, in this study, shared family environment had no impact on depression. Research also suggests that the risk of depression is associated with having of two or more first-degree relatives (parents, siblings, or children) with Alzheimer’s or Parkinson’s disease.
This high level of mortality in families with depression may be linked to heart disease. A significant number of studies show a relationship between depression and cardiovascular problems. Studies report the prevalence of major depression in cardiac patients as between 17 percent and 27 percent in hospitalized patients.
Serotonin may play a part in depression, but is also contributes to cardiovascular disorders. Serotonin plays a role in platelet aggregation, and platelet serotonin levels correlate negatively with severity of depression. In a clinical study University of Pittsburgh, blood platelet serotonin levels were 39 percent lower in patients who had made a suicide attempt.
Recently, scientists have discovered a gene that contributes to depression, called the serotonin transporter gene. Two forms of the gene have been discovered, described as the short and long gene form. Some studies suggest that inheriting the short form of the gene doubles the risk of depression, but recent studies found no correlation. Those who carry two copies of the short version of the gene are also more prone to alcohol abuse.
It has long been known that bipolar disorders also have a high genetic predisposition. The genetic penetrance of bipolar disorder is about 70 percent. What is not as well known is that bipolar disorder has also been genetically linked to cystic kidney disease, a disorder in which cysts growing in the center of each kidney cause them to malfunction. In one study, out of seven members with medullary cystic kidney disease, five had bipolar I disorder, one had unipolar depression, and one had a hyperthymic phenotype. Two known genetic loci of cystic kidney disease are found in regions of chromosomes 1 and 16 – areas that have been previously linked to bipolar disorder and schizophrenia.
The children of parents diagnosed with bipolar disorder are more likely to exhibit disruptive behavior disorders, separation anxiety disorder, generalized anxiety disorder, social phobias, or depression. These problems usually emerge in early or middle childhood.
Hagop Souren Akiskal, the director of the International Mood Center in San Diego, has found temperament dysregulation as an important familial genetic factor in the vulnerability for manic- depressive episodes. He believes that a trait known as hyperthymic temperament is a state often found in families with full-blown bipolar disorder. This temperament is characterized by upbeat, highly energetic, and overconfidence. People with these traits do not seek help for mental problems and, therefore, are rarely seen by mental health professionals. They often, however, will seek help for marital problems, job instability, or problems with impulse control.
“Many thoughts emerge in consciousness without having been summoned.”
Ralph E. Hoffman, MD
The schizophrenias plague about one percent of the world’s population. According to the National Institute of Mental Health, more than two million Americans are affected by some form of schizophrenia. This array of illnesses can severely impair a person's ability to manage emotions, interact with others, and think clearly. Symptoms include hallucinations, delusions, disordered thinking, and social withdrawal.
Although there are several treatments available today, the majority of people suffering from these maladies will suffer chronically or episodically throughout their lives. Even with treatment, one of every ten people with schizophrenia eventually commits suicide.
There seem to be genetic and epigenetic contributors to schizophrenia. The heritability of schizophrenia is about 70 percent. Several studies suggest that there is an increased risk of schizophrenia in people with older fathers. The risk of schizophrenia is increased for both males and female with fathers 55 years or older.
There is a peak in schizophrenia every three or four years, occurring at the same frequency as El Niño. The seasonal peak in schizophrenic births increases the further north a person resides. There is evidence that lack of UV light and low vitamin D may contribute to schizophrenia.
In 2006, scientists at Columbia University asserted that up to one fifth of all schizophrenia cases are caused by prenatal infections. Interestingly, Cox 2 inhibitors, which are powerful anti-inflammatory drugs, are an effective treatment for schizophrenia.
Patrick McCann, at the University of Oklahoma, has developed a diagnostic breath test that uses lasers to measure the amount of carbon disulphide in breath of children. Carbon disulphide is known to be at higher levels of in the breath of people with schizophrenia – even in infants. This allows him to make diagnoses decades before symptoms occur.
Family members of schizophrenics but without the disorders are at higher risk for other problems. For example, idiosyncratic use of language (a trait similar to the thought disorder observed in schizophrenia) occurs in 37 percent of clinically unaffected first-degree relatives of individuals with schizophrenia, a rate almost six times higher than the presence of schizophrenia in the same families. Other researchers have noted that family members of a person diagnosed with schizophrenia have a higher incidence of seizure disorders.
When the rates for thought disorder, schizophrenia, and related clinical conditions are combined, the proportion of potential gene-carrying relatives is close to 50 percent, consistent with a dominant gene, and much higher than the 6.5 percent rate of schizophrenia in the same families. Family members also have difficulty following a slow-moving target with one's eyes, syntax errors, or idiosyncratic use of language. Physically, they often have subtle anomalies in the midline of the face, and have difficulty filtering out noises and other irrelevant stimuli, a condition known as sensory gating.
Although methamphetamine does not cause schizophrenia, the greater familial incidence for schizophrenia, the more likely an amphetamine user in that family would develop psychosis and the longer that psychosis is likely to last.
Adverse experiences during gestation such as maternal stress and infection are known risk factors for neurodevelopmental disorders, including schizophrenia, autism, and attention deficit/hyperactivity disorder. Prenatal influenza virus infection has been associated with an increased risk of schizophrenia.
Mental symptoms of Wolfram Syndrome
Physical symptoms of Wolfram Syndrome
Type 1 Diabetes (between ages 5 and 15)
Wolfram Syndrome was first described in 1938 as a familial disorder usually presenting with Type 1 (juvenile-onset) diabetes and vision loss. The syndrome is an autosomal recessive disorder meaning that it only occurs in individuals who have received one copy of the gene from each parent. It is caused by a gene on the short arm of chromosome 4. The frequency of carrying the recessive genetic trait in the US population is approximately one percent.
The syndrome is also characterized by the presence of neurogenic bladder (frequent urination), hearing deficits, and other neurological problems. A majority of individuals who have two mutant Wolfram Syndrome genes have these distinctive symptoms. Despite the array of symptoms, most people will have the disorder for several years before an accurate diagnosis is made.
Wolfram Syndrome may also present with psychological symptoms, such as depression, violent and assaultive behavior, chronic anxiety, panic attacks, and hallucinations. Many attempt suicide. Most people with the disorder die prematurely with progressive, widespread atrophic changes throughout the brain. Unfortunately, 60 percent of those with the syndrome die by age 35.
While it takes two aberrant genes to manifest the full-blown syndrome, those who carry a single mutation, a condition called Wolfram Syndrome Heterozygotes, have no distinguishing physical characteristics but constitute approximately one percent of the population.
Family members who carry a single mutation in the Wolfram Syndrome gene are 26 times more likely to require hospitalization for depression and suicide attempts than people who do not have the gene. Researchers Ronnie and Michael Swift at New York Medical College estimate that even though only one percent of the general population carries the gene – about 25 percent of the patients hospitalized for psychiatric difficulties may be carrying the gene.
“Unfortunately, we have been misled into thinking that hereditary hemochromatosis is rare, and we do not yet think of iron overload as a somatic factor in the etiology of psychiatric illness.”
Paul Cutler, MD
Mental symptoms of hemochromatosis
Loss of sex drive
Cognitive and memory problems
Physical symptoms of hemochromatosis
History of multiple bacterial infections
Pains in the fingers, knees, hips, and ankles
Abdominal pain, diarrhea, or nausea
Setting off airport metal detectors
|Loss of body hair|
|Browning of skin similar to a suntan|
|Heart problems, such as arrhythmias|
|High serum glucose|
Hemochromatosis is a genetic disorder that causes iron accumulation in the body. People of Western European descent – with ancestors from Ireland, Wales, Scotland, or Great Britain – have a 20-40 percent probability of carrying a gene for hemochromatosis. According to the Centers for Disease Control, Type 1 hemochromatosis is the most common genetic disease in the United States.
Like Wolfram Syndrome, hereditary hemochromatosis is an autosomal recessive condition. The person must inherit two mutated genes (called HFE) one from each parent. This type of the disorder is deemed responsible for sexual dysfunction in 10-40 percent of men. They exhibit loss of libido and potency, and have high iron and low plasma levels of testosterone.
However, in some cases, inheritance of only one mutated gene may eventually lead to significant iron accumulation. Although the majority of these people will never know that they carry the gene, some will begin to feel aches and pains and changes in energy and mood. This condition is also thought to contribute to what is called treatment resistant mental disorders. A study by researchers David Feifel and Corinna Young Casey at the University of California in San Diego showed that 80 percent of people with treatment resistant bipolar disorder carried one gene and lacked a family history for this disorder. They estimated that one percent of psychiatric patients were likely candidates for iron overload.
Common symptoms of hemochromatosis are fatigue, aches and pains, disorientation, confusion, and memory problems. In these cases, the diagnosis is often missed for several years, as symptoms are mistaken for depression or dementia. Signs of the illness usually appear between ages 40 to 60, but some people show symptoms as early as 20. Patients suffering from idiopathic hemochromatosis exhibit low plasma levels of testosterone with loss of libido and potency.
It was Eugene Weinberg that was the first to look at the effect of iron in our bodies. He found that the presence of high iron could cause chronic inflammation. Hemochromatosis causes inflammation in the liver, joints, heart, lungs, pancreas, and the brain, especially in the basal ganglia. This part of the brain is rich in dopamine, and in these cases, iron may cause damage to the dopamine system contributing to many neurological disorders, including Parkinson's and Alzheimer's disease. The gene is thought to accelerate the onset of Alzheimer's disease by five years.
In the past, people with hemochromatosis usually did not survive past their forties or fifties. But as a result of better recognition and treatment, most people with the disorder now have normal life spans. This has resulted in another problem, iron overload in the central nervous system. Recent studies suggest that high iron stores are far more common in the elderly than had been previously realized, and may be a risk factor for Alzheimer’s disease.
Bloodletting has been a treatment for this illness for centuries and is still the treatment of choice. Another treatment is chelation therapy. We now know that lowering iron is not only useful for hemochromatosis, but may actually be beneficial to the immune system. Infections need iron to survive. When a pathogen enters the body, the immune system blocks the infection’s access to the iron store in the system to prevent its proliferation. The human body contains many natural chelators. For example, mother’s milk contains a substance called lactoferrin, a protein that prevents bacteria from absorbing iron.
Mental symptoms of Wilson's disease
Homicidal or suicidal behavior
|Unusual sexual behavior (including pedophilia)|
|Inappropriate behavior (especially sexual)|
|Deteriorating performance at school|
Wilson's Disease affects approximately 1 in 30,000 people worldwide, making it a rare disorder. However, it is estimated that at least half of the people with Wilson's Disease are never diagnosed, and therefore will suffer, and sometimes die, from the disease.
Wilson's is a genetic disorder that causes the body to retain copper. The liver of a person who has the disease cannot release copper into bile as it should. Over time, the copper reaches a toxic level and injures liver tissue. Eventually, this damage will result in high levels of copper in the bloodstream, which leads to damage in the kidneys, brain, and eyes. Untreated, high copper will eventually cause liver failure and brain damage.
Wilson's Disease occurs equally in men and women. Although some cases of Wilson's Disease can occur due to spontaneous genetic mutation, most cases are transmitted from generation-to-generation. The responsible gene is called ATP7B and is located on chromosome 13.
In order to inherit the disease, both parents must carry the gene. Siblings of Wilson's Disease patients have a one-in-four chance of having the disease. Since both of a siblings' parents are carriers, one-fourth of the siblings' children have the disease, one-half are carriers, and one-fourth are disease-free and carry no Wilson's Disease gene.
Children of Wilson’s patients have a one-in-two-hundred chance of having the disease. A child of a Wilson's Disease patient has a 100 percent chance of getting one abnormal gene. The patient's spouse has a one-in-one-hundred chance of carrying the abnormal Wilson's Disease gene, and half the time, he or she will pass it on. For this reason, all siblings and children of Wilson's Disease patients should be tested for Wilson's Disease. Other relatives who have had symptoms or laboratory tests that indicate liver or neurological disease also should also be tested.
Because Wilson's Disease is often mistaken for other maladies such as multiple sclerosis, Parkinson's disease, or psychiatric problems, medical specialists estimate that only about one thousand cases per year are ever diagnosed. In the early stages of the disease, especially when psychological symptoms occur, the diagnosis is often missed. In a study of misdiagnosis, Wilson’s was diagnosed in only one out of one-hundred-twenty-four patients. The delay between symptoms and diagnosis ranged from one to five years.
The most common of behavioral symptoms of Wilson’s Disease include personality changes, especially irritability and a low threshold to anger. Depression sometimes leading to suicidal ideation and suicide attempts is common. Deteriorating academic and work performance is present in almost all patients. Interestingly, many Wilson's Disease patients exhibit increased sexual preoccupation and reduced sexual inhibition. It is also linked with pedophilia.
A barrier to the diagnosis of Wilson's Disease is that most patients have no family history of it. Because both parents must carry the gene to manifest the disorder, people with only one abnormal gene usually have no symptoms, or may have mild, but medically insignificant, abnormalities of copper metabolism, and do not become ill.
People with Wilson's Disease may not have any outward signs, symptoms, or evidence of illness. However, people with mild or non-apparent Wilson's Disease will become seriously ill and eventually die if they are not treated.
Sometimes Wilson’s is diagnosed by the presence of the presence of Kayser-Fleischer rings, which are rusty-brown colored ring in the cornea. Diagnoses are usually made by blood and liver tests. Chelation therapy is commonly used as treatment. Doctors will also recommend avoiding foods high in copper such as liver, shellfish, mushrooms, nuts, chocolate, dried fruit, dried peas, beans and lentils, avocados, and bran.
Scientists believe the XXY condition is one of the most common chromosome abnormalities in humans. About one of every five hundred males has an extra X chromosome, but many have no symptoms. It is likely that about 60 percent of the cases are undiagnosed.
Klinefelter’s Syndrome is the XXY male with a set of observable symptoms. Symptoms depend on how many XXY cells a man has, how much testosterone is in his body, and his age when the condition is diagnosed.
Children with this condition will often exhibit attention deficit disorder. The syndrome is normally diagnosed during puberty. At this age, those with Klinefelter's Syndrome often have less facial and body hair and may be less muscular than other boys. They are often shy and have trouble fitting in with peers.
Mature men with this syndrome have several distinguishing characteristics, such as tall stature, long arms and legs, lanky build, feminized physique, little chest hair, female-patterned pubic hair, testicular atrophy, hypogonadism, osteoporosis, breast development, and low levels of testosterone. The low testosterone accounts for the lack of development of male secondary sex characteristics. They may be infertile and are more likely to have certain health problems, such as autoimmune disorders, breast cancer, vein diseases, osteoporosis, and tooth decay.
Behaviorally, they exhibit reduced aggression and lack of exploratory behavior. They also have trouble using language to express their thoughts and needs, but experience increased levels of emotional arousal. Problems with reading, trouble processing what they hear, emotional instability, and anorexia nervosa may occur. The main treatment is for this syndrome is testosterone.
It has long been known that certain families show tendencies for hyperthyroidism and hypothyroidism. What is not usually known is that members of such families are also prone to other conditions including insulin-dependent diabetes, pernicious anemia (lack of vitamin B12), premature gray hair, vitiligo (white spots on the skin), arthritis, and allergic conditions, including asthma, hives, and hay fever. There is also an increased tendency for members of these families to have various types of perceptual learning problems and dyslexia. Researcher Lawrence Wood suspects this relationship is missed because women in the family tend to get thyroid problems, while predominantly the men in the family have learning problems, but are seldom seen by family physicians. (See more on thyroid later in this document.)
DNA is found in every cell of the body. Another type is found in a part of the cell called mitochondria. Unlike cellular DNA, mitochondrial DNA is inherited from the mother. DNA in the mitochondria, therefore, identifies maternal risk factors of medical and mental illnesses.
Mitochondria are specialized organelles found in every cell of your body, except red blood cells. There are approximately 1,700 mitochondria in each human cell. They are vital to the production of cellular energy. In fact mitochondria are responsible for creating more than 90 percent of the energy needed by the body to sustain health. Inside the mitochondria, ingested sugar is broken down in the body by a process known as glycolosis, which changes glucose to a compound called adenosine triphosphate (ATP), which is then converted in to pyruvate. The pyruvate next delivered to tiny mitochondria. When this system fails, less and less energy is generated within the cell. Cell malfunction, and even cell death, may follow.
Diseases of the mitochondria appear to cause the most damage to cells of the brain. Mitochondria damage contributes to developmental delay, mental retardation, autism, dementia, seizures, atypical cerebral palsy, atypical migraines, stroke and stroke-like events, and other psychiatric disturbances.
In early 2000, researchers Kato Tadafumi and Kato Nobumasa at the University in Tokyo proposed a mitochondrial dysfunction hypothesis for bipolar disorder. Postmortem tissue samples extracted from the hippocampi of the brains of nine individuals with bipolar disorder showed significant mitochondrial depletion. A search for mutant mitochondrial DNA in the tissue samples revealed two suspect genes.
A Cleveland Clinic survey of 38 outpatients with mitochondrial diseases found 70 percent met the criteria for major mental illness, including 54 percent with lifetime depression, 17 percent with lifetime bipolar, 11 percent with lifetime panic, and 11 percent with current generalized anxiety. On average, the mitochondrial disease was diagnosed about four years after the onset of psychiatric symptoms, and 14 years after a physician was seen for diagnoses. Genetic testing has helped significantly in identifying mitochondrial risk factors.
“Learning itself consists of nothing more than switching genes on and off.”
Out of our 30,000 genes, only two percent of deoxyribonucleic acid (DNA) codes for proteins. Until very recently, much of our DNA was considered to be what researchers call junk DNA. These genes were considered to be the byproduct of millions of years of evolution – genes were still inherited but were no longer used. Recently, however, scientists have discovered that some of this junk DNA actually switches on RNA that interacts with other genes.
The field of research of these phenomena is epigenetics. Epigenetics is the science of turning genes on- and-off with nutrients and other chemicals, resulting in changes of expression of those genes. The process of suppressing and enhancing genes is called methylation, a chemical process that, among other things, aids in the transcription of DNA to RNA and is believed to defend the genome against parasitic genetic elements called transposons.
Transposons are spans of DNA that – through a process called transposition – can actually move to different positions within the genome of a cell.
Transposition was first observed by researcher Barbara McClintock; this discovery earned her a Nobel Prize in 1983. As a result of her work, geneticists now know that this process can be activated by changes in diet, drugs, and exposure to toxins, and can permanently change a person’s DNA.
More fascinating is the finding that these mutations may be inherited by children. Environmental toxins have been shown to alter the activity of genes through at least four generations after exposure. For example, women who smoke while pregnant double the risk of asthma in their grandchildren.
For this reason, no two brains are alike, including those of identical twins. It is thought that about 40 percent of our genes can be modified epigenetically. Although identical twins share the same DNA, their epigenetic material can be different. Moreover, the older the twins become, the more discrepancies will occur in their DNA. Fifty-year-old twins have four times as many differentially expressed genes than three-year-old twins.
Even more interesting is the discovery that genes are regulated by maternal care. Thus far, at least nine hundred genes can be altered by maternal care. For example, the presence of a variation in the monoamine oxidase A gene (MAO-A) combined with maltreatment predicts antisocial behavior.
In mid-2009, researcher Moshe Szyf at McGill University reported that commonly-used pharmaceutical drugs can cause such persistent epigenetic changes. Szyf and his co-author Antonei Csoka posit that drug-induced diseases, such as tardive dyskinesia and drug-induced lupus, are epigenetic in nature. (More about Lupus below.) They also propose that epigenetic changes from pharmaceuticals may be involved in heart disease, obesity, diabetes, infertility and sexual dysfunctions, as well as neurological and cognitive disorders.
Smoking can cause changes in gene function. As stated earlier, there is compelling evidence that prenatal smoking increases the incidence and severity of ADHD. The risk of a severe type of ADHD greatly increases in children whose mothers smoked during pregnancy and who also have variants of one or two genes associated with ADHD – one on chromosome 11 and the second on chromosome 5. Interestingly, even children of mothers who smoked during pregnancy who didn't fit all of the criteria for ADHD had more symptoms of the disorder. This was true if they had been exposed to cigarette use in utero or had genetic variations related to risk.
“We only use ten percent of our brain.”
Attributed to Albert Einstein
The early human embryo consists of three cell layers: the mesoderm, endoderm, and ectoderm.
The mesoderm forms muscle and bone. The endoderm creates the cells lining the digestive and respiratory system. The ectoderm forms the skin, hair, fingernails, olfactory system, and neural cells, including the brain. This is intriguing, since people with hair, skin, nail, and olfactory problems seem to be more prone to mental disorders, which will be discussed later.
The brain begins from a miniscule layer of tissue called the neural plate. As the fetus continues to grow, there is neuronal migration up the plate to the head. The average human baby generates an astonishing 50,000 neurons per second during gestation.
In the developed brain, there are two essential types of cells – neurons and glia. (The word glia is derived from the Greek word for glue). Although we usually think of neuron problems when we look at mental disorders, 90 percent of brain cells are glial cells; only 10 percent are neurons. Unlike many neurons, glial cells are able to divide and reproduce rapidly. Glial cells surround neurons and hold them in place, supply nutrients and oxygen to neurons, insulate one neuron from another, and remove dead neurons.
University of California at Berkeley professor Marian Diamond has been one of the pioneers of the theory that an enriched environment increases brain function. Years ago, Dr. Diamond obtained a slice of Einstein’s brain. Comparing a cortical region associated with higher cognition of Einstein’s brain with eleven control brains, she found Einstein’s brain had significantly more glia.
It had long been thought that glial cells were protectors of neurons. However, in the early 1960’s, Diamond and other researchers discovered that the cortices from rat pups living in enriched environments contained more glial cells per neuron than those from impoverished environments. This suggests that that the environment in the early years sculpts the brain.
Astrocytes are a type of glial cell that surround the synapses between neurons. It appears that a dearth of these cells plays a part in mental illness. Postmortem studies on human brains of individuals with major depression or bipolar disorder have detected significantly lower than normal levels of glial cells.
A reduction in the number of glial cells in the prefrontal cortex has been observed in people who are clinically depressed. There are alterations of glial cells in schizophrenia. Astrocytic damage is also found in multiple sclerosis, temporal lobe epilepsy, amyotrophic lateral sclerosis, lupus, human immunodeficiency virus (HIV) dementia, Alzheimer’s disease, and traumatic injury, all of which may present as mental disorders.
The function of astrocytes is to supply neurons with energy, meaning a low astrocyte level would cause lower activity in the associated neurons. Sodium valproate is a sodium salt of valproic acid used in the treatment of epilepsy, bipolar disorder, and a mood stabilizer. Valproic acid protects dopaminergic neurons in midbrain neuron and glia cultures by stimulating the release of neurotrophic factors from astrocytes.
Researcher Serge Przedborski, the co-director of the Center for Motor Neuron Biology and Disease, has found that astrocytes with a mutated form of a gene, superoxide dismutase (called SOD1), kill neurons, which eventually is seen as amyotrophic lateral sclerosis.
“Talk therapy needs to address our biological selves as well as our psychological selves.”
John Ratey, MD
Research presented at the Second World Congress on the Fetal Origins of Adult Diseases suggests that osteoporosis may actually begin in the womb. If a baby is undernourished, she will be small at birth, will be small at the first year, will often have low bone mass at 25, and will have a high probability of bone trauma at 70 and a high probability of hip fractures at 70. Low bone mass is also linked to schizophrenia, depression, and other mental problems.
Scientists now believe that many disorders – including mental disorders – have their origins in the early stages of life. For example, low birth weight is correlated with depression after puberty. Low birth weight was not the only cause but increased the risk effects of other adversities, such as child abuse.
The volume of the human brain increases more during the first year of life than at any other time; therefore, early physical health plays a part in brain development. Researcher JWB Douglas found that children who had at least one admission to the hospital for more than a week's duration, or who had repeated hospital admissions before the age of five years, had significantly increased risk of behavior disturbance and poor reading in adolescence. The children were more troublesome in school and at home, and more likely to be delinquent in school. As adults, they were prone to show unstable job patterns than those who were not hospitalized in their first five years. Although this type of historical data would be most helpful in making a diagnosis, it is rarely sought in an intake interview.
Besides early illness, early nutrition also has lasting consequences. During the early years, nutrition is allocated in ways that give the child the best chance in early life, sometimes at the expense of later years.
In the era of the Baby Boomers, formula was considered by many doctors as superior to breast milk. Most baby boomers were bottle fed babies. In one study, premature babies fed only standard-formula milk had noticeably lower IQs at school age than breast-fed infants, and they were particularly bad at mathematics. A small area of their left parietal lobe was less active than expected.
The developmental phenomenon called programming allows a fetus to adapt to sub-optimal conditions, such as malnutrition. In some cases, this can have an effect on brain development which could be the precursor to a mental disorder later in life.
There are sensitive periods for growth; if not exposed to environment at the proper time, brain development is altered. For example, language is acquired in the first few years of life.
Neural Pruning is the deletion of cells. Over one-third of the neurons in the cerebral cortex are eliminated in the first three years. At six months, babies can differentiate human and non-human faces, such as monkey faces, but by nine months, they lose this ability to discriminate monkey faces. Since the monkey face discrimination is not needed, it is deleted. Some researchers believe that pruning is also responsible for dementia. The theory is that, late in life, the pruning system is turned on and cells begin to be deleted.
Cortical migration and neuron proliferation are complete at five and twelve months of age, respectively, while myelination is only 50 percent complete at eighteen months after birth. Seventy-five percent of human brain growth occurs during the first two years; the remaining 25 percent is not completed until adulthood.
Brain size in the newborn is proportionately greater than in adults. The newborn brain weighs one-third of an adult brain, while the newborn weighs only four percent as much as the average adult.
The blood-brain barrier, which restricts the penetration of toxins to the brain, is not fully developed in humans until about one year of age. It is not known when the barrier becomes fully functional. Connections in the visual system are not fully achieved until three or four years of age. Brain development differs between boys and girls, with girls generally reaching peak gray matter thickness one to two years earlier than boys.
Breastfeeding significantly decreases the risk of cognitive and behavioral problems. In full-term infants, increasing the duration of breastfeeding (more than eight months) is associated with consistent and statistically significant increases in IQ (assessed at ages eight and nine) reading comprehension, mathematical ability, and scholastic ability (assessed at ages ten to thirteen).
While I am not suggesting that you measure the head of you clients, head size does correlate with mental function. The phrase “egg head” comes from the observation that people with large heads tend to have high IQ’s.
It has long been noticed that head size is correlated with intelligence. Larger head size is related to higher tests scores in global cognitive functioning and speed of information processing. These observations are not confounded by educational level, socioeconomic background, or height.
Large head size may also protect people against cognitive deterioration during aging, which supports the “reserve hypothesis” of brain aging.
People with small head size (defined as less than 21.4 inches in circumference), and the presence of the Apo ε4 gene are 14 times more likely to develop Alzheimer’s disease. However, large head size is also correlated with social spectrum disorders. There is also a correlation between small head size and schizophrenia.
“But the issue of sexual harassment is not the end of it. There are other issues - political issues, gender issues - that people need to be educated about.”
Humans tend to identify themselves as male or female. But, in fact, gender identity is a continuum.
Researcher Simon Baron-Cohen states in his book, Prenatal Testosterone in Mind, that the default fetal brain structure is female. In a male fetus, testosterone is released at the seventh week, which changes the brain structure to that of a male. How and when this occurs may play a part in gender behavior and identity. Several studies suggest that gay men are more likely than either lesbians or heterosexual men to have older brothers, but not older sisters. Researchers Gualtieri and Hicks posit that this may occur because of a maternal immunization effect.
A mother carrying her first son has very little exposure to the proteins he is making because of the placental barrier. However, with each delivery the inevitable mixing of fetal and maternal blood occurs, and her immune system is exposed to proteins it has never seen before encoded on her son’s Y chromosome. Her immune system responds to these proteins, and subsequent sons will be exposed, via active transport across the placenta, to antibodies directed against male-specific proteins, which then perturb development of the younger son. This decreases birth weight and affects the events that masculinize the brain.
Many years ago I began working with Tom, an engineer in a rocket manufacturing company, who had called me for what he said were “phase of life” problems. When Tom arrived I asked him, “How can I help?” to which he replied, “I am forty years old.” “So, how can I help” I again replied. “Well, statistically most men my age are married and have two children. I have never been married, and therefore is seems clear that I should do so now.” He then opened his briefcase and pulled out a three-ringed binder. “I have here a list of character traits that I would like to have in my female partner, and I want to read them to you so that you can tell me in what habitat I might find such a person.“
Clinical empathy is an essential requirement for effective psychotherapy. It is the way we bond with our clients and it is also the way we assess the level and depth of their suffering.
Empathy is hard-wired in the brain. It is one of the fundamental traits in pair bonding. Therefore, the brain has multiple circuits for understanding the emotional state of others. Human brains are remarkably alike. They all contain cerebral hemispheres, a corpus collosum, white matter, and other structures that mediate behavior, thought, and mood. Subtle architectural changes, however, can have a profound change in these capacities.
Research suggests that the default genetic blueprint of a human brain is a right-handed female. At the seventh week of gestation, the male fetus begins to secrete testosterone, and this lateralizes the brain. Among the changes from female to male architecture is the pruning of the corpus collosum. Savants – people who often have remarkable abilities with memory, math and music – frequently have a significantly smaller corpa collosa.
Autism is one of the most heritable mental disorders. If one identical twin has it, there is a 90 percent probability that the other will also have the disorder. If one child in a family has autism, siblings have a 35-times greater-than-normal risk of symptoms.
It is important to know if anyone in your client’s family has a diagnosis of an autism spectrum disorder. Relatives of children with autism spectrum disorders are at a higher risk of having mild development impairments, including language delays and impairments in social skills and social gestures, and are more likely to exhibit attention deficit disorders.
Alexithymia means “no words for feelings.” It is a state predominantly seen in males. People exhibiting alexithymia have a difficult time speaking about, or even being aware, of their feelings. Interestingly, researchers have found that alexithymia and engineer’s syndrome is often seen in people with hair loss, skin diseases, anxiety and depression. (See the skin and hair sections below).
Engineer’s syndrome (which is not a mental illness) is a state of not only having trouble identifying one’s own feelings, but also a deficit in understanding other’s feelings. Feelings are often seen as bothersome or useless. People with these traits are often depicted by family and friends as cold, distant, and nonassertive.
While these traits are not mental disorders, they frequently play a part the person’s social life. Research suggests that alexithymia often acts as a trigger for many medical and psychiatric disorders. This also contributes to marriage and family problems. Spouses and family will often complain that the person is cold, aloof, and non-caring.
This state of being seems to be hardwired early on in brain development. Researchers suggest that this deficit is in part caused by a smaller corpus collosum, the part of the brain that connects the left and right hemispheres.
In the developing brain, the right hemisphere is dominant for the first three years of life. This hemisphere modulates primitive emotions, emotional perception, and nonverbal communication. Researcher and author Alan Schore believes that attachment makes possible the emergence of affect regulation, located in the right orbital prefrontal area, but others believe the predisposition for this is hard wired.
Von Economo neurons (discovered by researcher Constantin von Economo) thus far have only been found in humans, the great apes, humpback whales, fin whales, killer whales, sperm whales, and African and Asian elephants. These neurons are found in the human insular cortex and the anterior cingulate cortex – both areas of the brain that mediate intuition, humor, trust, empathy, mood, pain, and what researchers call theory of mind. It is these circuits that allows us to pair bond and react to another person’s distress.
Certain disorders such as antisocial behavior, frontal dementias, and Parkinson’s show low levels of these neurons. People with deficits in the corpus collosum tend to have low counts of these neurons.
The mirror neuron system in the human anterior cingulate is considered crucial for human imitation; people who fit the criteria for engineer’s syndrome do not exhibit neurophysiological responses to other people’s pain and discomfort. The mirror neurons of many children with autism spectrum disorders respond only to their own movement.
From 1987 to 1998, the California State Department of Developmental Services reported a 273 percent increase in autistic disorders, while the state population grew only 19 percent. The increase did include cases of high-functioning autism or Asperger's. Many researchers today believe that this meteoric increase is that people who have mild tendencies like engineer’s syndrome are more likely to marry each other. A generation ago, men with engineer’s syndrome would seek out a spouse with superior social skills because they knew they had deficits, but now they are marrying women with the same disposition.
“Sinistrality is nothing more than an expression of infantile negativism.”
Abraham Blau 1946
“The percentage of left-handedness is much higher in the abnormal class of people.”
Most humans are right-hand dominant, but there are a growing number who are not right-handed. Being right- or left-handed is partially determined by genetics. If a person inherits the gene for right-handedness, that person will be right-handed. But those who do not have the gene may be either left- or right-handed. There is no specific gene for left-handedness.
If identical twins carry the right-hand gene, both will be right-handed. But if they lack the gene, one twin may be right-handed, while the other may be left-handed. On average, the probability of two right-handed parents having a left-handed child is about 9 percent; two left-handed parents’ probability is 26 percent; and one left-handed and one right-handed parent have a probability of 19 percent. Currently, approximately 13 percent of the population is left-handed. Generally, males are three times more likely to be left-handed than females. Several studies report that gay people have a 39 percent probability of being left-handed, although there is still controversy about these findings. People who can use both hands equally well are ambidextrous. True ambidexterity is rare.
The Latin word for left is sinister, which is defines as “threatening or foreshadowing evil or tragic developments.” For generations, left-handers who attended Catholic schools were forced to become right-handed.
Many left-handed people have a penchant for mathematics and the sciences. In fact, more than four-fifths of youngsters enrolled in the Johns Hopkins program for mathematically precocious youths (defined as kids who scored 700 on the math SAT when they were 12 years old) were allergic and/or left-handed. Members of Mensa, the high IQ club, also have a far higher than normal incidence of allergies.
Left-handedness has also long been coupled with mental disorders. There is a higher rate of depression in left-handed people. A 2008 study found that in children with developmental coordinational disorder, 31 percent were left-handed, and 13 percent were mixed dominant. Being left-handed is more common in alexithymia and is also closely related to engineer’s syndrome, Asperger’s, and autism. Being "a lefty" is also correlated with social anxiety, shyness, and embarrassment.
In general, left-handers are also known to have a higher incidence of allergies, asthma, eczema, and autoimmune diseases. Doctor Lawrence Wood at Massachusetts General Hospital has noted that there is a 17 percent incidence of left-handedness and ambidexterity in patients with Grave's Disease, Hashimoto's disease, and primary hypothyroidism, as well as in family members. Autoimmune diseases in general seem to be associated with left-handedness, mixed dominance, and learning disabilities.
“The body is responding to what's going on in the brain, not to what's going on in the environment.”
Margaret Kemeny, Ph.D.
The sneezing and runny nose you have makes you miserable. You don’t feel like eating. The aches and pains and lethargy make you want to go to bed and sleep for a week. You don't feel like doing anything. Getting up to pay the bills seems like an overwhelming task, and you can't even focus on the book you took to bed with you. All you want to do is sleep.
The above is a good description of the common cold, but if you take away the sneezing and runny nose, it also looks a lot like depression.
The immune system is the part of the body that that fights infection. When the body has a cold, the immune system goes to work by attacking the virus with an array of special cells, proteins, and organs.
Immune system cells are white blood cells called leukocytes. These cells are manufactured and stored in many sites in the body, especially in the thymus, spleen, and bone marrow. In addition, throughout the body are groups of cells called lymph nodes that house leukocytes. Leukocytes constantly circulate through the blood vessels, but they also travel through the body by way of the lymphatic system.
Researchers have suspected for many years that infections can lead to mental illness. In fact, in an editorial entitled Is Insanity Due to a Microbe? published in Scientific American in 1896, the authors described injecting cerebrospinal fluid – taken from mentally ill patients – into rabbits that later became ill. Syphilis, once considered to be a common mental illness, was eventually found to be caused by a virus.
There was a lull in research during the era of psychoanalysis, but in 1973, psychiatrist and researcher E. Fuller Torrey at the Stanley Medical Research Institute in Chevy Chase published a series of articles suggesting that microbial infections could cause mental illness.
In the last decades, it has become clear that microbes and pathogens are the cause of many mental illnesses. It now appears that schizophrenia, autism, bipolar disorder, and other mental problems are linked to various infections, including fungal, viral, and parasitic infections. These infections can attack the nervous system during pregnancy, childhood, or later life. While some infections directly affect the brain, others trigger immune reactions that interfere with brain development or perhaps even attack our own brain cells in an autoimmune mistake.
More than 200 studies have suggested that schizophrenia occurs between five to eight percent more frequently than average in children born in the winter or spring. Viruses are most prevalent in the cold winter months. In 2006, researchers at Columbia University suggested that one-fifth of schizophrenias are caused by prenatal infections. It has also known that streptococcus can, if left untreated, lead to serious psychiatric problems.
The mapping of the human genome has revealed connections between genes, microbes, the immune system, and mental illness. An alteration of genetic markers in a particular population has also been shown to provide resistance to specific diseases. For example, schizophrenia has been shown to have a strong inverse correlation with rheumatoid arthritis, such that one disorder protects against the other. The burgeoning field of research linking the immune system and mental health is called psychoneuroimmunology.
“For the last fifty years the tendency of medicine has been to isolate single disease characteristics of the individual and look for single agents to treat those characteristics.”
Jeffrey Bland, Ph.D.
The immune system and the brain are alike in two fundamental ways. Both have the capability to store new information in a form of memory and both are able to recall that information in response to an appropriate stimulus. Both systems have an intricate network of synaptic connections and also share a number of messenger molecules, such as cytokines and chemical mediators
There is only one type of immune cell inside the brain – microglia. Microglia cells are similar to immune cells found in the body, called macrophages. Microglia do not mount much of an immune response in the brain. In fact, in some instances they made even be harmful to brain cells. The body’s immune system talks to the brain, and in some cases, damages it.
Jerome Posner has found that a tumor – anywhere in the body – can lead to degeneration of specific brain regions by means of molecular mimicry. Antigens from the tumor cells induce antibodies that trigger immune responses both in the tumor and in the brain. This can lead to an immune attack on the brain resulting in neural damage. For example, inner uterine cancer may cause damage to the cerebellum. The clumsiness that is caused by this damage may appear years before the cancer is diagnosed.
Posner found that certain types of tumor cells expressed the same target protein that was the antigen under attack in neurons. The term paraneoplastic syndrome is a disorder or set of symptoms that is triggered by cancer in the body, but is not due to the local presence of cancer cells. Patients with paraneoplastic psychological disorders have a reactive immune response to the tumor. A similar autoimmune attack against the brain is damage to the myelin sheath, found in multiple sclerosis.
The same molecule that is involved in cell-to-cell recognition in the immune system also seems to play a major role in the brain’s developmental wiring process. In animals, this molecule is called the major histo-compatibility complex, commonly cited as MHC, a cluster of genes located on chromosome 6 concerned with antigen production and critical to the success of transplantation. The MHC includes the human leukocyte antigen (HLA) genes.
When a pathogen is noticed by the immune system, molecules take a fragment of the pathogen's peptide, which is then displayed to a certain type of immune cell, so it can identify the pathogen and attack it. In the developing brain, the same molecule appears to be essential for one brain cell to determine which other brain cell to which to connect. This suggests the same family of genes may be involved in a recognition process of cells in the immune system and the nervous system.
Cytokines (a word originating from the Greek words cyto-, meaning cell, and kinos, meaning movement) are a number of substances that are secreted by cells of the immune system that carry signals locally between cells and have an effect on the other cells.
The immune system is a messenger that alerts the brain to infection or injury by releasing proteins called proinflammatory cytokines. The brain releases its own cytokines that signal the central nervous system to help the body adapt by reducing energy output.
Increases in certain cytokines (often interluekin-1, interluekin-6, and tumor necrosis factor alpha) induce fatigue, anorexia, weight loss, sleep disturbance, loss of libido, memory problems, anhedonia, and irritability. These behavioral changes are referred to as sickness behavior. It has been observed that couples and family members with high levels of cytokines tend to fight more often.
“Finding the causes of the immune activation and chronic secretion in psychiatric diseases will be the keys to unraveling the mystery of ‘mental’ illness.”
Ronald S. Smith, MD
In autoimmune disorders, the immune system mistakenly attacks the body's healthy organs and tissues as though they were foreign invaders.
In the last few decades, there has been a dramatic increase of allergic and autoimmune diseases, such as asthma, eczema, allergic rhinitis, multiple sclerosis, Type 1 diabetes, and inflammatory bowel disease (including Irritable Bowel Syndrome and Crohn’s disease) in developed countries. In addition, the increase of intestinal permeability seen in these disorders is also seen not only in healthy relatives, but also in spouses of these patients, suggesting these problems may be transferred by pathogens.
At the same time, the number of people with mental disorders has also risen dramatically. A significant number of these maladies are thought to be caused by immune dysregulation. Epidemiologic studies suggest that the overuse of antibiotics is connected to a reduction in the incidence of infectious diseases throughout the lifespan, which results in a compromised immune system.
In the last few years, it has become evident that the immune system can attack and disorder the brain.
In fact, the bulk of recent research of the cause of mental illness has shifted from neurotransmitters to immune dysfunctions. Many of these disorders respond to therapies that target autoimmune response.
Rheumatoid arthritis is a chronic, progressive autoimmune disease. The disease causes and joint destruction, disability, and significant pain. It is estimated to affect about one percent of adults worldwide, increases in prevalence with age, and affects more women than men.
The magnitude of the severe long-term economic consequences of the malady has been underestimated in the past. Most people with the disease require continuous treatment to retard or stop its progression and to control disease flare-ups. Many will require surgery, such as total hip or knee replacements. In addition to these direct costs, work disability leads to reduced productivity and early retirement, and as a result, substantial indirect costs. The disease commonly results in premature mortality, resulting in a mean reduction in life expectancy somewhere between 5 to 10 years. Those suffering with arthritis often experience loss of self-esteem, fatigue, mental distress, and depression.
Mental signs of Lupus
Medical symptoms of Lupus
|Loss of appetite|
Lupus is a chronic disease that often manifests as muscle pain, joint pain, and inflammation. The abnormal immune response may also involve attacks on the kidneys and other organs. Ninety percent of cases occur in women of childbearing age.
The medical term for lupus is systemic lupus erythematosus, or SLE. Erythema is a redness of the skin caused by dilatation and congestion of the capillaries, which is often a sign of inflammation or infection.
The word Lupus means wolf and, interestingly, Lupus is also found in dogs. Some researchers believe that Lupus patients have infected the dogs.
Lupus is an autoimmune disease, meaning that the immune system malfunctions and attacks the body’s own cells and tissues. The age of onset in Lupus is generally in the mid-to-late 20s, but African-Americans tend to get a more severe variant of the disease with an earlier onset.
The disorder is believed to be genetic. Certain ethnic groups, including those of African, Asian, Hispanic/Latino, Native American, Native Hawaiian, and Pacific Island descent, have a greater risk of developing Lupus. It often appears in certain families. When one of two identical twins has Lupus, there is an increased probability that the other twin will also develop the disease. Although Lupus can develop in people with no family history of the malady, there is often a presence of other autoimmune diseases in family members.
The prevalence of Lupus is significantly higher in females than in males. It is the most common cause of stroke in young women. While it is posited sex-linked genes may contribute to this, other studies suggest sex hormones, especially estrogen and prolactin, are a factor. Despite the evidence of genetic vulnerability to date, no gene or group of genes has been proven to cause the disorder.
Lupus is usually triggered by environmental events, exposure to sunlight being one well-known trigger. It may cause mood and anxiety disorders, particularly major depression and generalized anxiety disorder.
The diagnosis is made by a variety of clinical examinations and blood tests. Sixty years ago, SLE was an uncommon disorder, affecting an estimated three to four individuals per 100,000. Today, the estimated prevalence of this disease has increased by about four to fifteen times.
Lupus often presents with severe fatigue, painful joint swelling, and persistent skin rashes, but it can affect any organ system in the body including kidney disease, blood clotting, and central nervous system diseases.
The symptoms of Lupus can be ethereal and vague, making the diagnosis difficult. The symptoms can vary so much that it may be misdiagnosed as many other illnesses. It often presents with mental symptoms and may be initially diagnosed as a mental disorder. Gastrointestinal inflammation from Lupus can cause eating problems that may be misdiagnosed as anorexia.
Although the disease most often presents as pain or profound fatigue, it can also cause cognitive and emotional problems. Some will experience forgetfulness and irritability. It is believed that the cause of these problems is vascular injury of the intracranial blood vessels. Cognitive disturbances and memory loss are common problems in Lupus patients, but the disease can also present as a psychosis, major depressive disorder, or personality disorder, often of a histrionic type. In fact, it is believed that more than half of people with Lupus will present with mental problems. For many, the first noticeable physical symptom is a butterfly-shaped rash on the face.
This type of presentation has frequently been labeled as neuropsychiatric systemic lupus erythematosus (NPSLE). Even so, the diagnosis of Lupus is often missed in patients with mental disorders. For example, in 1992, researcher Neil Hopkinson tested three hundred hospitalized psychiatric patients for auto-antibodies in serum samples and found that one-in-one-hundred patients had undiagnosed Lupus. As a result of these findings, Hopkinson recommends that tests for Lupus be done in every patient with a high erythrocyte sedimentation rate in psychiatric services.
Drug induced Lupus, sometimes called DILE, is an autoimmune disorder similar to systemic Lupus, which is brought about by certain drugs. It is caused by an autoimmune response producing symptoms similar to those of classic Lupus. Thus far, there are about 40 medications that can trigger this problem. The highest number of cases, however, are caused by hydralazine, brand name Apresoline, which is a vasodilator used to lower blood pressure; procainamide, brand name Pronestyl; quinidine, brand name Quinaglute – both of which are used for cardiac arrhythmias; and isoniazid, brand name Laniazid or Nydrazid, which is an anti-tuberculosis medication.
Drug-induced Lupus symptoms include fever, elevated blood pressure, skin lesions, muscle and joint pains, and significant fatigue. Generally, the symptoms recede after discontinuing use of the drugs.
Decreased levels of DHEA have been found in people with autoimmune disorders like Lupus and immune deficiency syndrome. There is some evidence that DHEA can improve symptoms of these disorders. In a twelve-month, double-blind, placebo-controlled trial of 381 women with mild or moderate Lupus, the effects of DHEA at a dose of 200 mg daily reduced many symptoms of the disease.
Physical symptoms of Sjögren’s
Salivary gland enlargement
|Recurrent otitis media|
|Frequent dental caries|
Mental symptoms of Sjögren’s
Sjögren's Syndrome is a chronic autoimmune disease in which white blood cells attack the moisture-producing glands. It is one of the most prevalent autoimmune disorders; it is estimated that about four million Americans are suffering from Sjögren’s Syndrome. Nine out of ten are women.
The hallmark symptoms are dry eyes and dry mouth, but Sjögren’s may also cause dysfunction of the kidneys, gastrointestinal system, blood vessels, lungs, liver, and pancreas. Many patients will have joint pain.
It produces a higher risk of developing lymphoma. It has a similar to presentation to multiple sclerosis and Lupus. All three disorders have an unpredictable course with waxing-and-waning of symptoms.
Sjögren's Syndrome is known to affect the central nervous system and often manifests itself as a mental disorder. It most commonly presents as an atypical mood disorder, but can also cause, psychosis, dementia, somatization, dissociation, panic attacks, and personality changes.
"Aberrant genes do not, in and of themselves, cause disease. By and large, their impact on an individual’s health is minimal until the person is plunged into a harmful environment."
Jerry Bishop and Michael Waldholz
Mental symptoms of candida
|Low sex drive|
Physical symptoms of candida
Cravings for sweets
Antibiotics have saved millions of lives. They are one of the reasons that we have increased our longevity. However, there is a correlation between the time line of the discovery and use of antibiotics and the rise of autoimmune disorders – the drugs that are saving lives may be causing long-term illnesses.
Yeast occurs in all humans. It normally resides in the intestinal tract, mouth, throat, and genitals. In most people, the presence of the yeast has no symptoms. However, antibiotics change the bacterial balance in the gut, causing an opportunistic infection of a yeast called candida albicans.
Candida fungi are especially found in denture wearers. The warmth and wetness between the denture and the roof of the mouth is a perfect habitat for the yeast. A Korean study found that in 38 people with antibiotic-associated diarrhea, the common yeast Candida was present in the stool cultures of three participants, while four had evidence of the bacterium costridium difficile (C. difficile) in their stool.
Women with recurrent vaginal candidiasis were significantly more likely to suffer clinical depression, to be less satisfied with life, to have poorer self-esteem, and to perceive their lives as more stressful. Additionally, women with recurrent vaginal candidiasis reported that their candidiasis seriously interferes with their sexual and emotional relationships.
There is a connection between chronic yeast infections, candida, and mercury poisoning. It is thought that the body produces the yeast as a defense against excess heavy metals. The yeast cells absorb their own weight in mercury, which prevents the metals from entering the blood stream. The amount of mercury that candida cannot ingest is excreted as methyl mercury.
In some cases of obsessive compulsive disorder (OCD), infection with the bacteria streptococcus may be a contributing cause. Researcher Susan Swedo replaced the blood plasma of 28 children who suffered from OCD and had elevated levels of streptococcus antibodies with healthy donor plasma. Within a month, the incidence of tics declined by half and their other OCD symptoms were reduced by 60 percent.
The pathogen has now been implicated in other disorders. Anorexia nervosa has emerged or has worsened after a case of strep throat. Streptococcus has also been implicated in Tourette’s Syndrome, personality changes, anxiety, attention deficit disorder, disruptive behaviors, and depression.
Dyskinesias are purposeless and involuntary movements. It is now known that streptococcus can trigger Sydenham's Chorea, a disorder that causes the arms and legs of those afflicted to jerk in a manner often likened to dancing. Recently, the spectrum of post-streptococcal movement disorders has been expanded beyond chorea to include motor and vocal tics, dystonia, narcolepsy, and myoclonus. The prevalence of similar movement and emotional disorders in first-degree family relatives suggests that a genetic predisposition is important in disease development, in addition to an environmental event.
Mental symptoms of Lyme disease
|Attention deficit hyperactivity disorder|
Physical symptoms in Lyme disease
|Sensitivity to light and sound|
Lyme disease is an infectious illness which often causes psychological symptoms. The disease is transmitted to humans by an infected female Ixodes tick. Because this tick is smaller than the dog tick and because the bite is not painful, the tick is often unnoticed. The infection requires that the tick feed for at least 12-24 hours. The ticks are most commonly carried by deer and by the white-footed mouse, but other carriers have been found as well.
The first recorded case of what is now known as Lyme disease was recorded in 1883 in Breslau, Germany, by Alfred Buchwald, a physician who described a skin disorder now known as acrodermatitis chronica atrophicans (ACA). In 1921, Doctor Arvid Afzelius published a paper describing a rash he suspected had been caused by the bite of an insect called the Ixodes tick.
In 1970, the first case of Lyme disease in the United States was reported by Rudolph Scrimenti, who diagnosed and treated a patient who had been bitten by a tick while hunting grouse in Wisconsin. In 1976, the first U.S. case of clustering of this disease was reported in Lyme, Connecticut, by researchers at the Naval Submarine Medical Laboratory. In 1977, Allen Steere and his associates described the first clustering of a disease which was misdiagnosed as juvenile rheumatoid arthritis. The malady is now called Lyme arthritis.
Researchers Willy Burgdorfer, Jorge Benach, and Edward Bosler were studying the outbreaks of Rocky Mountain spotted fever in the 1980's. While examining the ticks, Burgdorfer noticed a parasite in the body fluid of two ticks. As the result of his discovery, the bacteria have been named Borrelia burgdorferi. His research also confirmed that this bacteria was the cause of Lyme disease.
In 1985, Lyme disease researcher Paul Duray reported that Lyme disease bacteria infects multiple systems in the human body. In the same year, Burgdorfer was able to confirm that infected ticks could be found across the entire United States. Today, Lyme disease is the most common insect-borne infection in the United States. In the last decades, it has been rapidly increasing in incidence.
The disease often presents with a red, round, expanding rash within days or weeks after the bite. This is often followed by flu-like symptoms. After one or two months, there may be cardiac symptoms such as low heart rate and low blood pressure, myopericarditis (inflammation of the wall of the heart), left ventricle dysfunction, and cardiomegaly (enlarged heart).
Soon after, vision problems and nervous system symptoms begin. Early on, patients may begin to suffer frequent headaches. Conjunctivitis may also emerge. Other symptoms include profound fatigue, extreme sensitivity to sounds (called auditory hyperacusis), sleep problems, and sensitivity to light (photophobia).
Psychological symptoms include agitation, irritability, emotional lability, paranoia, psychosis, dementia, bipolar disorder, anxiety, panic attacks, depression, anorexia, and obsessive-compulsive disorder.
Sometimes alterations in taste and smell occur. By six to ten months after the infection, many people will begin to suffer from arthritis in multiple joints.
Neurological problems such as meningitis, encephalitis, or mild to severe marked mental symptoms occur. After two to eight years, the infection will cause chronic mental problems. Because of this, patients with Lyme disease are often referred to mental health professionals before and after diagnosis.
In a 1994 study, researcher Brain Fallon found that 40 percent of patients showed alterations in brain function. Depression is very common, and in some studies 66 percent of sufferers show depressive symptoms. Impairments also occur in short-term memory, concentration, learning, and conceptual ability, suggesting problems in the frontal lobe. Cognitive problems include difficulty with word-finding, dyslexic-like errors when speaking or writing, and spatial disorientation.
Interestingly, the prevalence of schizophrenia in the United States is highest in the urbanized Northeastern, Northwestern, and Great Lakes States. These areas also have the highest presence of Lyme disease. In other parts of the world, the incidence of tick-borne encephalitis are also most prevalent in countries that also have the highest rates of schizophrenia, including Germany, Ireland, Finland, Croatia, and Norway.
Because the number of cases of the disease is rapidly increasing, Lyme disease should be included in the differential diagnosis of any mental health assessment. In its mechanism of infecting the body, Lyme disease is similar to syphilis, meaning it can cause damage over several decades. For this reason, early detection is essential. In the early stages, it is treatable illness, but once the disease invades the central nervous system, it can become chronic.
Because diagnostic tests are not always reliable, clinicians often must often rely on the observable symptoms to make a diagnosis. Factors that suggest this diagnosis include knowledge of a tick bite, or having been in a geographic area known to be in an area inhabited by ticks, a history of skin rash, joint pains, arthritis, cardiac problems, and symptoms that began after a flu-like illness.
“Viruses have a special affection for nerve cells.”
Nancy Andreasen, MD. Brave New Brain
Borna is a 750-year old town in Saxony, Germany. Borna disease got its name in 1885 when the town began to suffer an epidemic of illness in horses. The owners of the animals were bringing them to veterinarians, describing them as listless, fatigued, and sad. The horses were eventually found to have a virus that had never been seen before.
Once the virus was identified, research began. In 1924, Wilhelm Zwick successfully transmitted Borna disease to rabbits. This marked the beginning of systematic studies to determine the pathogenesis of the disease. In 1909, Ernst Joest and Kurt Degen found that the virus caused changes in the brain, especially within ganglion cells of the hippocampus. Since then, the virus has been detected in sheep, birds, cattle, cats, primates, and humans. So far, it is seen in Europe, Asia, Africa, and North America. Interestingly, in Germany since the mid-1960s, the incidence of Borna disease has declined significantly.
Recent findings have implicated the borna virus in human neurological and psychiatric conditions including schizophrenia, obsessive-compulsive disorder, panic disorder, and mood destabilization.
The virus is found frequently in people with recurrent major depression or bipolar disorder.
Those who suffer a depression tend to have severe angst and deep despair, which often leads to hospitalizations.
In schizophrenia, it is believed that the virus may insinuate itself into the fetal brain at a crucial stage of development, which subtly deranges the brain's neural connections. This disarray only becomes apparent as the brain reaches maturity in late adolescence to early adulthood.
Researchers believe that once a person has been infected by the virus, he may develop Borna disease, or possibly act as a carrier of the virus.
Amantadine, originally used in the treatment of influenza infection, has proved beneficial in people with borna virus. The antidepressive effect is comparable to prescription antidepressants; however, higher doses of amantadine may cause confusion, hallucinations, and nightmares.
There is controversy about how amantadine works. While some believe it works by destroying the virus, others contend that it actually works as an antidepressant. Researchers point out that the drug is also effective in treating Parkinson's disease, traumatic head injury, dementia, multiple sclerosis, and cocaine withdrawal.
Although an association between antibodies to herpes virus and cognitive functioning have not been found in people without psychiatric disorders, infection with herpes simplex virus 1 is a predictor of cognitive dysfunction in individuals with schizophrenia and bipolar disorder. The cognitive deficits found in schizophrenia and bipolar disorder are similar to those found in people who have recovered from central nervous system infections with human herpes. Physical or emotional abuse lowers the antibodies for herpes, increasing outbreaks significantly.
Physical symptoms of Hepatitis C
The word Hepatitis means inflammation of the liver. Hepatitis C is an infection of the liver caused by the hepatitis C virus. It is difficult for the human immune system to eliminate the virus from the body, meaning that the infection usually becomes chronic. Seventy-five percent of people who contract the virus will carry it for life. Twenty percent will eventually develop cirrhosis of the liver.
Hepatitis C was discovered in 1989. Today, approximately four million Americans are infected with the hepatitis C virus, and it is estimated that approximately 170 million people are infected worldwide, which is equivalent to three percent of the world's population. Eighty percent of those who are infected will remain asymptomatic for years.
Research shows patients with chronic, severe mental illness have four to nine times the prevalence of the virus. Conversely, most patients with Hepatitis C infection present to medical clinics with active psychiatric and substance use disorders. A 2005 research paper by Marian Fireman at the Northwest Hepatitis C Resource Center found that screening Hepatitis C patients for mental problems revealed that 93 percent had a current or past history of at least one mental disorder. Seventy-three percent had two disorders. The most common disorders were depression (81 percent), posttraumatic stress disorder (62 percent), any substance use disorder (58 percent), and bipolar disorder (20 percent).
Chronic HCV infection often presents as anger, hostility, anxiety, chronic fatigue, lassitude, and depression. It can also manifest as a mild subcortical dementia. At the present time, treatment for chronic Hepatitis C is a 24-48 week course of alpha interferon and ribavirin.
Symptoms of neurocysticercosis
|Violent and abusive behavior|
Neurocysticercosis is a central nervous system infection caused by accidental ingestion of eggs of Taenia solium, a pork tapeworm found in contamination food. Most people are infected by consuming raw or undercooked pork. It is one of the most common parasitic causes of neurological diseases in developing countries. Approximately two-and-a-half million people worldwide carry the adult tapeworm. Many more are infected with the eggs.
Although the infection is predominantly found in Latin America, Africa, and South Asia, the high rate of international travel and immigration makes it a health issue throughout the globe. As of 2010, it is estimated that about 50 million people worldwide are infected. It is estimated that 200,000 people in the United States are infected. In the U.S., the disease is most prevalent in Texas, New Mexico, and California. One study reported neurocysticercosis as the cause of 2 percent of the neurologic and neurosurgical admissions in southern California.
Although neurocysticercosis is not a highly prevalent disorder, it is the most common worm infection of the central nervous system. It can present as depression, psychosis, or cognitive deterioration, and is also known to cause seizures. During the early phase of the infection, many people will present with disorientation, and visual and auditory hallucinations, often followed by apathy, euphoria, memory impairment, and a slowing of cognition. The illness is generally diagnosed as a mental disorder. It is not until motor problems and seizures develop that the diagnosis is made.
Toxoplasma gondii (usually called T. gondii) is one of the most interesting of all parasites. It has actually found a way of reproducing itself by changing the brain of its host.
Rats have a built-in fear and dislike of cat urine. This innate fear prevents rats from being eaten by cats. However, rats infected with T. gondii lose their fear of cat urine. In fact, it makes them attracted to the scent of cats, which makes them easy prey. The cats then become infected by eating infected rats. Cats then infect humans who handle infected cats or their feces.
This infection can change a human brain and actually alter a person’s personality and behavior. Men infected with the pathogen tend to become more likely to disregard rules. They are more suspicious, jealous, and dogmatic. They also have slower reaction time and six-fold higher risk of traffic accidents. Curiously, infected women often show more warmth and self-confidence.
This is a common human infection. Most people are unaware that they are infected. However, an acute infection with this parasite can produce psychotic symptoms similar to those displayed in people suffering from schizophrenia and Alzheimer's disease. Since 1953, there have been several studies verifying T. gondii antibodies in people with schizophrenia. The majority of the studies found a higher percentage of antibodies to T. gondii in affected persons.
Other studies have found that exposure to infected cats in childhood is a risk factor for the development of schizophrenia. In pregnant women, infection with Toxoplasma can cause abortions and stillbirths. The virus can also cross the placenta and infect the fetus. In these cases, the infection may cause changes in head size, such as hydrocephaly or microcephaly; mental retardation; seizures; deafness; cerebral palsy; and damage to the retina. Increased ventricular size and cognitive impairment may also occur – symptoms that also occur in some people with schizophrenia.
Curiously, several medications used to treat schizophrenia also inhibit the replication of T. gondii in cell culture. When human cells raised in petri dishes were infected with Toxoplasma, the growth of the parasite stopped when haloperidol was put in the dish. Haloperidol (Haldol) is an antipsychotic used to treat schizophrenia.
A blood test can check for antibodies to the parasite. Medications for adults include pyrimethamine (Daraprim) plus either trisulfapyrimidines or sulfadiazine. In pregnancy, spiramycin is usually given.
Spiramin, considered an experimental drug in the United States, is sometimes is obtained by special permission from the FDA specifically for Toxoplasmosis in the first trimester of pregnancy.
the people are many and their hands are all empty.
Where the pellets of poison are flooding their water."
Bob Dylan, Hard Rain
The Industrial Revolution brought technology that changed the world forever. Factories and machinery allowed unprecedented productivity, but with production came significant pollution. Humans need air, water, and food to survive, but we have now managed to contaminate our atmosphere, oceans, streams, rivers, and food supply. The number of chemicals that can cause neurotoxicity in laboratory animals exceeds 1,000. Thus far, researchers have found that at least 202 manmade chemicals have the capacity to damage the human brain.
Behavioral toxicology and behavioral teratology are the fields of research that investigate the consequences of exposures to toxins, including cognition, learning, memory, and behavior. Researchers agree that currently the most troublesome neurotoxins in our environment are metals, solvents, pesticides, and pharmaceuticals.
These pathogens, along with hundreds of other manmade molecules, have permanently permeated our bodies and our minds. The first international symposium in behavioral toxicology was in 1973. Since that time, researchers have concluded that all people alive today carry in their bodies at least 700 contaminants. This conglomerate of toxins has been deemed body burden.
Of concern are the 32,000 hazardous waste sites in the United States. At the time of this writing, more than 1,100 public schools – serving 600,000 children – are located within half-a-mile from contaminated sites in California, Massachusetts, Michigan, New Jersey, and New York.
There is evidence that environmental toxins play a part in poor school performance. For example, environmental polycyclic aromatic hydrocarbons (PAH) at levels recently encountered in New York City air are thought to adversely affect children’s cognitive development at three years of age.
Toxins, such as heavy metals, can cause cytokine release and destabilization of the hypothalamus-pituitary-adrenal axis. This can cause changes in the brain, manifested as psychological symptoms.
Although there is a massive amount of research of toxins and mental health, people with mental problems rarely are seldom screened for toxicity. In all the years I practiced outpatient psychotherapy, the thought of getting a toxicology assessment never crossed my mind.
The clearest data on the deleterious effects of prenatal exposure to toxins comes from the study of two metals, lead and mercury, and from epidemiological investigations of the effects of alcohol intake during pregnancy.
"For researchers who operate at the intersection of basic biology and toxicology, following the data where they take you – as any good scientist would – carries the risk that you will be publicly attacked as a crank, charged with scientific misconduct, or removed from a government scientific review panel."
Herbert L. Needleman
Physical symptoms of heavy metal toxicity
Heavy metals have long been known to cause problems with the central nervous system. The dissemination of these substances in our environment has caused significant mental problems in people of all ages. Children are especially vulnerable to adverse effects of multiple metals exposure.
Treatment for heavy metals is chelation therapy in consultation with clinicians experienced in lead toxicity therapy. Some of the best known heavy metal toxins follow.
“Chronic mercury exposure has reached a critical level where inorganic mercury deposition within the human body is accumulating over time. It is logical to assume that the risks of associated neurodevelopmental and neurodegenerative diseases will rise as well.”
Dan R. Laks, MD
Mental symptoms of mercury
Physical symptoms of mercury toxicity
|Impaired motor function|
In June 1997, Karen Wetterhahn, a 48-year-old Dartmouth College cancer researcher, whose specialty was dangerous heavy metals, died of dimethyl mercury poisoning 10 months after she spilled several drops on her rubber gloves.
She was studying how mercury prevents cells from repairing themselves. Two months after the spill, she began losing her balance and having speaking and hearing difficulties. At three months after the spill, Wetterhahn experienced two serious episodes of nausea and vomiting. Soon after that, she was hospitalized. Tests showed 80 times the lethal dose of mercury in her blood. Soon after, she slipped into a coma and, within weeks, died. Tests after her death revealed that the mercury had passed readily through her rubber latex gloves without damaging them.
Mercury is an extremely neurotoxic element. Methylmercury consists of a methyl group bonded to a mercury atom. A methyl group is the portion of an organic molecule derived from methane gas, created by removal of a hydrogen atom. Methane was originally called "marsh gas" because it was first isolated from the gas bubbling out of marshes. Methane is produced by certain bacteria that live in oxygen-free environments such as estuaries, lake-bottom sedimentation, sewage, and mud. This is how mercury gets into the food chain.
For many years, methylmercury has accumulated in our environment. As a result, each year, about 60,000 children are born at risk of developmental deficits, including decreased school performance, as the result of exposure to methylmercury in the womb, usually caused by the mother’s consumption of contaminated fish.
Great Lakes fish consumption by pregnant women is associated with decreased birth weight and deficits in cognitive function in their infants and children.
Mercury can disrupt the endocrine system, causing dysfunctions of the pituitary gland, thymus, and adrenal glands. It has also been observed that mercury can have significant effects on thyroid function. Disruption of hormonal functions occurs at very low levels of exposure. This abnormality can occur even though hormone levels remain normal making the usual thyroid tests inadequate for diagnosis.
In animal studies, PCBs (a type of pesticides) and methylmercury act synergistically to reduce dopamine in the brain. Adverse health effects, which include neurological problems, have been well-documented.
Although the main source of mercury exposure in the environment is methylmercury from seafood, inorganic mercury comes from other sources, such as high fructose corn syrup (found in many processed foods) and mercury vapor from dental amalgam fillings. Assessing the consumption of these foods can lead to the assessment of mercury toxicity.
For many years, mercury was used in dentistry in dental amalgam, a filling material used in repairing tooth decay. Even today, the most commonly used amalgam is made of approximately 40-50 percent mercury, 25 percent silver and a 25-35 percent mixture of copper, zinc, and tin. Amalgam use is declining because the incidence of dental decay is decreasing and because better substitute materials are now available for dental cavities.
Dental fillings containing mercury have always been a center of controversy. The FDA, the Centers for Disease Control and Prevention, and other government agencies have reviewed the scientific literature looking for links between dental amalgams and health problems. In 2001, the Centers for Disease Control stated, “there is little evidence that dental amalgam impacts the health of the vast majority of people who have them.” They also report that removing amalgam fillings has no beneficial effect on health.
The United States Food and Drug Administration (FDA) considers dental fillings to be medical devices, and have been regulated since the 1990s. In 2002, the FDA published a proposed rule to classify dental amalgam as a class II medical device with special controls. On April 28, 2008, the FDA reopened the comment period for that proposed rule. After reviewing all comments, the FDA intends to issue a final rule classifying dental amalgam. In January 2008, Norway and Sweden completely banned mercury fillings. Shortly thereafter in April 2008, Denmark also banned mercury fillings.
Since dental offices are known to be one of the largest users of inorganic mercury, researchers have assessed mercury in dentists and personnel who work in dental offices. Mercury vapor accumulates in their bodies in much higher levels than non-occupationally exposed. In fact, mercury levels of dental personnel average at least two times that of controls.
Mercury poisoning is often misdiagnosed as mental problems. The metal especially damages the liver, the immune system, and the pituitary gland, all of which play a part in mental function. Chronic mercury exposure increases the risks for autism and dementing illnesses such as Alzheimer's disease. It also presents as depression, chronic anger, and anxiety. There are several ways to test mercury in the body, including blood and hair tests.
"One molecule of lead, when it enters a cell, will change the state of that cell."
Symptoms of lead toxicity
Short-term memory loss
Inability to concentrate
|Abdominal and joint pain|
Measurements of the bones of humans before the Industrial Revolution show that the natural level of lead in human blood was 0.016 micrograms per deciliter. Currently the United States government's level of concern for lead is 10 micrograms per deciliter – a level 625 times as high as the natural environmental level.
Lead is a potent neurotoxin. Exposure to lead during pregnancy or during childhood results in deficits in intelligence quotient (IQ) and in other behavioral problems.
In school research studies, teacher’s report an increasing number of problems – such as somatic complaints, anxiety, depressed behavior, social problems, attention problems, and delinquent and aggressive behavior – in grade school children. The incidences of these behaviors correlate with the children’s serum lead levels. An interesting finding was that abused children are 27-fold more likely to have high serum lead levels. Bone lead levels are related to self-reports of delinquent acts. Families who live in houses built before 1978 have higher lead exposures, but those living in homes built before 1940 have a significant higher risk of lead exposure.
Although there are few studies of lead in older adults, one study of older women with blood lead levels as low as eight micrograms per deciliter showed significantly poorer cognitive function. As people age, bone mass decreases. As bones deteriorate, the amount of lead stored in bone becomes a significant source of lead in the bloodstream. Older workers with previous occupational exposure are at risk for recirculation of lead in blood with advancing age.
Physical symptoms of cadmium poisoning
Respiratory tract damage
Loss of bone mineral density
Pure cadmium is a silvery white metal with a subtle bluish hue. Most of the cadmium in the environment occurs from activities such as mining, smelting, and refining metal ores – especially zinc, lead and copper. The United States is the world’s primary producer of cadmium, generating an estimated 1,100 tons of the metal per year. Fertilizers and nickel-cadmium batteries contain significant levels of cadmium.
The metal is readily absorbed by sea life, particularly shellfish. Because of this, in the United States, the Environmental Protection Agency has issued fishing advisories related to cadmium for coastal waters around New York, Connecticut, and New Jersey. The highest levels of cadmium in food are found in shellfish, such as oysters and clams, and in the liver and kidneys of animals.
Unlike many trace elements, there is no role for cadmium in the human body. In the body, cadmium interferes with calcium metabolism, leading to loss of calcium in human tissue and bones. Most of the metal will accumulate in bones, liver, and kidneys, where it can cause damage. Cadmium is known to cause kidney disease, high blood, pressure and heart disease.
On average, people consume about 30 micrograms of cadmium daily through a normal diet, of which one to three micrograms are absorbed into the body. Cigarette smoke contains cadmium. Cadmium inhaled through cigarette smoke is more easily taken up by the body, allowing from 40 to 60 percent of the cadmium inhaled in smoke is absorbed into the human bloodstream.
Mothers who smoke during pregnancy tend to have children of smaller birth weight, which is a risk for neurological disorders, including deficits in social behaviors. Children often are exposed to cadmium by cigarette smoke from their parents. At school age, children's urinary cadmium levels are linked with immune suppressive effects. Cadmium has also been linked to behavioral problems and learning disabilities.
"Like the constant dripping water that wears away the hardest stone, the birth to death contact with dangerous chemicals may in the end prove disastrous. Each of these recurrent exposures, no matter how slight, culminates in the progressive build-up of chemicals in our bodies and so the cumulative poisoning ... the average citizen is seldom aware of the deadly materials with which he is surrounding himself; indeed, he may not realize he is using them at all."
Rachel Carson, Silent Spring (1962)
Mental symptoms of pesticide poisoning
Inability to concentrate
For three decades in the United States, dichloro-diphenyl-trichloroethane (known as DDT) was used to control insect pests on crop and forest lands, for homes and gardens, and for industrial and commercial purposes. Within a few years, millions of birds died.
As a result of Rachel Carson’s campaign, DDT was banned in 1973. However, it continues to be detected in the organs and tissues of people in the U.S. Later on, under the Stockholm Convention, DDT was banned for agricultural use worldwide. What is not well known is that DDT is still used in disease vector control throughout the world. India, China, and North Korea still produce and export DDT, and production is reportedly on the rise. Currently, India is the largest consumer of DDT. The current global use of DDT for disease vector control is four-to-five thousand tons per year. Food is the primary source of DDT. The adverse effects of DDT are particularly devastating to children.
Currently in the United States, there are more than 900 chemicals registered as pesticide; there are about 350 pesticides actively used in the U.S. People are exposed to pesticides through use in homes, gardens, and on pets, consuming residues on food, drinking contaminated water, and being exposed due to wind drift from nearby spraying.
As insecticides increase in the body, they are broken down into other chemicals. One common chemical found in human urines is 3,5,6-trichloro-2-pyridinol, often called TCPY. In 2003, the Second National Report on Human Exposure to Environmental Chemicals found that more than 90 percent of men have detectable levels TCPY in their urine. In adult men, TCPY is associated with reduced testosterone. Low testosterone has a significant impact on mood, behavior, and cognition. (For more on this, see the chapter on testosterone.)
Higher levels of 1-naphthol (a product known as Sevin) in men’s urine are associated with decreased sperm concentration. Prenatal exposure to pesticide can also result in low sperm count in a child. Studies suggest that if a pregnant woman is exposed to a pesticide at the wrong time, her children, grandchildren, and the rest of her descendants could inherit the damage and diseases caused by the toxin. The over-the-counter anti-ulcer drug Tagamet (cimetidine) has been shown to inhibit the breakdown of semen in both laboratory animals and humans.
Other consequences of pesticide exposure include depression and suicide. Suicide rates are high in farming populations. Animal and human studies have linked organophosphate exposure to acetylcholine and serotonin disturbances in the central nervous system, neurotransmitters that are implicated in depression and suicide in humans.
Polychlorinated biphenyls (usually called PCBs) are classified as persistent organic contaminants that accumulate to toxic levels in the food chain and pose a major threat to human health.
Organophosphate pesticides cause serotonin disturbances in the central nervous system, which are implicated in suicide. Pesticide exposure and at least one defective copy of the gene CYP 2D6 29B+ predict an 83 per cent probability of Parkinson’s disease with dementia. People who work on farms have a high incidence of Parkinson’s. In addition, suicide rates are high in farming communities.
An interesting study of 29,074 the female spouses of private pesticide applicators indicated that, although the women did not apply pesticides, they were often exposed to them because they lived on the farm and sometimes helped prepare the pesticide. This population had a high level of major depression, often requiring medication.
The long-term implications are even more serious. Researcher Michael Skinner has found that when pregnant rats were exposed to a pesticide at a certain time, four generations of their descendants inherited the damage and diseases caused by the toxin, even if it did not involve a genetic mutation. Although this was an animal study, Skinner believes that this can also occur in humans. This is considered as an epigenetic reason that a mental illness could be found in multiple family members.
Symptoms associated with perfluorooctanoic acid (PFOA) exposure
|Increased cancer rates|
|Changes in lipid levels|
Many synthetic carpets contain arsenic, benzene and other volatile solvents. There are significant positive associations between atopic eczema and wall-to-wall carpets, but out-gassing of toxins in carpets can also cause depression, mood swings, agitation, dysphoria, and confusion.
The chemical perfluorooctanic acid (PFOA) is used to make fluoropolymers, substances that make flame-resistant carpets (also used for water repellent clothing and food wrappers). Scotchgard®, which is used to protect carpets, fabric, and upholstery, and Teflon®, are made from PFOA.
The Environmental Protection Agency has pressured companies to discontinue the use of PFOA, because of evidence of low birth-weight and reproductive health problems. The substance also causes liver damage, thyroid disorders, immune disorders, and cancer, all of which can present initially as mental disorders.
“The priest is to go in and inspect the house. He is to examine the mold on the walls, and if it has greenish or reddish depressions that appear to be deeper than the surface of the wall, the priest shall go out the doorway of the house and close it up for seven days.”
Mental symptoms of mold
Mold spores are present in all indoor environments. In most cases, these molds do not cause illness, but exposure to molds and their associated mycotoxins in water-damaged buildings can cause a multitude of health problems, including disorders in the central nervous system and immune system, both of which cause mental disorders.
Stachybotrys and Aspergillus versicolor are common molds that destabilize brain function. The symptoms of stachybotrys often mimic Alzheimer's disease. Several studies report that people with mold exposure have a symptom array very similar to those who suffer mild traumatic brain injury.
Mold exposure is frequently misdiagnosed as fibromyalgia, chronic fatigue syndrome, or Lyme disease. It often presents as anxiety, depression, or dysphoria.
Medications associated with psychological problems
|Histamine 2 blockers|
|Cancer chemotherapy agents|
There is a troubling phenomenon afoot in the United States. Most psychotropic drugs are now prescribed by physicians and nurse practitioners, not psychiatrists. Even worse, a New England Research Institute study of antidepressant found that 43 percent of people who have been prescribed antidepressants had no psychiatric diagnosis, no assessment, nor any mental health care beyond the prescription of the drug. These medications are usually prescribed by family physicians, often given usually at the request of the patient who had seen the drug on a television advertisement.
Unknown to the person requesting the drug is the troubling finding published in the Journal of the American Medical Association that the risk of suicidal behavior is increased in the first month after starting antidepressants, especially during the first one to nine days. There is often no follow-up by the prescriber.
Even more disturbing is the finding in a 2006 study that three-quarters of people prescribed antidepressant drugs receive the medications for reasons not approved by the FDA. The majority of these drugs are prescribed for women. There is evidence that pregnant women should not be taking these drugs. Babies exposed to Effexor and other SNRIs and SSRIs late in the third trimester of pregnancy have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. These complications can arise immediately upon delivery.
When a patient is using psychotropics, it is important to ask how long the drug has been used and how effective it has been. Ask for permission to speak to the prescribing practitioner. Ask for any workups or lab tests used to make the diagnosis.
Although it is well known that mental problems can be caused by medications, there is little research exploring these phenomena. Clinical studies are seldom done because adverse medication reactions are sporadic, idiosyncratic, and unpredictable. Unfortunately, these problems are usually noticed only after a drug has been approved, when anecdotal adverse reports begin to accumulate.
Drugs are chemicals that change biochemical systems in the body. Therefore, any drug that has an effect on the body also has the potential to demonstrate adverse effects. A conservative estimate is that at least 60 percent of all prescription drugs cause psychiatric problems. A recent survey states that psychiatric side-effects are actually listed on over 65 percent of pharmaceuticals. These medications may cause mental problems directly or may activate latent mental disorders.
In most cases, medical professionals who prescribe medications do not alert their patients about potential side-effects. In fact, a recent study showed that over 65 percent of patients were not told by their doctors about any adverse reactions of a drug, and 67 percent of patients were not told anything about potential side-effects.
Although it is impossible to address all problematic medications, here are some examples of medications known to cause emotional, cognitive, and behavioral difficulties:
Medications for Parkinson's disease and restless leg syndrome are dopamine agonists, meaning that they increase the level of dopamine in the central nervous system. These medications are advertised vehemently and are becoming more popular. Although the majority of consumers of the medications do see an abatement of symptoms, about one-in-five patients using these medications will exhibit problems, including pathologic gambling, excessive shopping, and hyper-sexuality. Requip, a popular dopamine agonist, has been found to cause people to fall asleep, without warning, during daily activities. This sometimes occurs as late as one year after the person has been taking the drug.
A large percentage of patients taking the prostate cancer medication Leuprolide Acetate report short-term memory loss, depression, emotional lability, insomnia, dizziness, and anxiety.
Researchers have now confirmed that there are toxic interactions between pharmaceuticals and chemicals to which we commonly exposed on a regular basis. Long-term chronic exposure to organic solvents, which are found in materials such as paints, printing inks and dry cleaning agents, has been linked to long-term cognitive impairment, fatigue, clumsiness, and depression. In addition to pesticides, 55 contaminants have been detected in popular products sold as a lawn and garden fertilizers. The combination with medications and environmental toxins can be disastrous. Here are some examples:
Side effects of cimetidine
In the summer of 1985, Thomas Latimer, a healthy 30-year-old was mowing his lawn. After about an hour, he began to experience dizziness and nausea, followed by a severe headache. Each day, he became worse. For the next six years, Mr. Latimer was unable to exercise and began to have seizures. In the next few years, he visited 20 different doctors. His symptoms were consistent with organophosphate poisoning, most likely from the insecticide that had been applied to his lawn. However, his symptoms were so severe, and the amount of pesticide he was exposed to was so low, the doctors looked look for a synergistic factor.
After extensive testing and research, a toxicologist, three neurologists and two neuro-ophthalmologists all concluded independently that the popular ulcer drug Tagamet (cimetidine) – an over-the-counter antacid – had made him more vulnerable to the pesticide. His doctor, Alfredo A Sudan, a professor of neurology and ophthalmology at the University of Southern California, stated that “Tagamet can make a person 100 to 1,000 times more sensitive to organophosphate poisoning.”
Tagamet can also cause trouble with concentration, irritability, severe headaches, agitation, restlessness, disorientation, and hallucinations. Tagamet impairs acid secretion in the stomach, which blocks the absorption of ionic iron (the iron found in vegetables). A review of the literature shows that central nervous system side-effects can occur within 24 hours of treatment with the drug. They are often unrecognized or misdiagnosed by clinicians, and are reversed within 12-to-48 hours after the discontinuation of the medication.
Side effects of statins
Transient global amnesia
Every cell in your body contains cholesterol. It makes each cell waterproof. It also participates in the formation of new memories, and allows the uptake of serotonin.
Statins are one of the most prescribed medications in the U.S. The most common side-effect of the drug is muscle pain and weakness, but other side-effects – not listed in the package insert – are transient global amnesia (the sudden and temporary loss of memory), cognitive impairment, memory problems, low sex-drive, dizziness, depression, and suicidal ideation. There have also been cases of severe irritability, homicidal impulses, threats to others, road rage, and damage to property. A 1997 Norwegian study reported that psychiatric disorders represent 15 percent of adverse reactions to statins.
Side effects of Proton Pump Inhibitors
Proton pump inhibitors came on the market in 1988, as omeprazole (Prilosec). Since that time dozens of similar drugs have hit the market. The drugs work by blocking stomach acid production. To date, they are the most potent inhibitors of gastric acid secretion available.
Gastric acid is a key defense against gastrointestinal infections. Unfortunately, lowering stomach acid increases the risk of an increasingly common infectious form of diarrhea caused by a proliferation of Clostridium difficile bacteria, also known as C-diff. In fact, a 2008 study done in the UK showed that 64 percent of all patients who developed C. diff infections were on proton pump inhibitors.
People taking these drugs also have higher incidence of helicobacter pylori. Infections in the GI system are well known to be connected to mental problems, such as depression and anxiety. These medications also interfere with the absorption of vitamin B12 and vitamin D. The lack of B12 is known to present as mental disorders. In some people, the use of these drugs can cause anxiety, aggression, confusion, and depression.
A medication can be said to cause mental symptoms only when the symptoms occur when the drug is delivered and when symptoms abate when it is withdrawn. However, the problem becomes difficult to assess when the person is taking more than one medication.
In addition, many people taking prescription drugs are also taking over the counter medications, herbs, vitamins, and supplements, which can interact with medications.
Polypharmacy has become a serious problem. For this reason, it is mandatory to get a complete list of your clients’ prescription and over-the counter medications, as well as herbs, vitamins, and neutraceuticals.
Unfortunately, we no longer have to be using pharmaceuticals in order to have problems with them.
A new source of pharmaceutical, hormone, and organic chemical ingestion is our water supply. Thousands of substances have now been detected in streams across the entire United States, many which can alter brain function. Although adverse drug-effects are monitored by the FDA, most pharmaceuticals are not regulated by the Environmental Protection Agency.
The human endocrine system consists of two basic types of glands: endocrine and exocrine. Exocrine glands are also called duct glands, which include mammary glands, sweat glands, salivary glands, and the stomach, liver, and pancreas. The products of these glands do not enter the bloodstream. Endocrine glands secrete substances called hormones into the bloodstream that regulate metabolism in other tissues, including the central nervous system.
The endocrine system is mediated by two regions of the brain called the hypothalamus and the pituitary gland. The hypothalamus is actually a group of small nerve cells near the bottom of the brain. The hypothalamus controls many body functions such as temperature, respiration, and sleep architecture. It also controls the pituitary gland, which then sends messages to the thyroid and the adrenal glands. This circuit is called the hypothalamic pituitary axis (HPA).
There is universal agreement that 50 to 75 percent of patients with major depression exhibit hyperactivity of the HPA axis. It has also been found that people with generalized anxiety disorder have deficits in the regulatory mechanisms of the HPA associated with an abnormal response to stress.
The question is, then, what causes the HPA axis destabilization? We do know that aging and depression change the HPA system in similar directions. This is one reason that older adults are more prone to depression. It has also been found that antidepressants affect the HPA system by reducing its activity.
It may, in part, be that antidepressants also seem to have an anti-inflammatory affect. Although there are many ways to alter this axis, one of the more common causes of HPA axis destabilization is inadequate intake of omega 3 fatty acids.
“The most plausible explanation for the association between geomagnetic activity and depression and suicide is that geomagnetic storms can desynchronize circadian rhythms and melatonin production,”
Kelly, Posner, PhD. Columbia University in the US.
The pineal gland is a tiny pinecone-shaped organ (hence the word pineal) located at the back of the brain, just above the brain stem. The major function of this gland appears to be the stabilization of the circadian rhythm. This is the fundamental circuit of the internal balance known as well-being.
Melatonin, the hormone secretion from the pineal gland, is enhanced in darkness and decreased by light exposure. As melatonin is secreted each night, it helps us fall asleep. Generally speaking, melatonin and serotonin are not active in the body at the same time. Melatonin is active at night; serotonin is active in the daytime. Dysregulation of this rhythm can cause mood disorders.
In addition to sleep, melatonin has many other functions. It controls the timing and release of female reproductive hormones, affecting menstrual cycles, menarche, and menopause. Melatonin inhibits the release of cortisol via the release of oxytocin. This is interesting in that studies show that oxytocin plays a role in orgasm, social recognition, pair bonding, anxiety, trust, love, and maternal-pair bonding behaviors.
As well as being a central nervous system hormone, melatonin is also found in the skin and digestive tract. For this reason, melatonin is found to play a part in peptic ulcers. Stress and dietary habits can lead to deficiencies of both serotonin and melatonin. Pineal receptor cells are connected to the hypothalamus, as part of the HPA axis.
Children have the highest levels of nocturnal melatonin, but with age, nocturnal melatonin levels get lower and lower, which is manifested by the tendency for aging adults to go to bed earlier and wake up earlier. It is also common for older adults to suffer from disrupted sleep patterns.
For these reasons, one of the common uses of melatonin supplements is for treatment of insomnia. Yale dermatologist Aaron B. Lerner was the leader of a team of researchers who discovered melatonin in 1958. The hormone became available over the counter in 1994. When this product was initially released to the public, everyone believed that it would be the most effective treatment for insomnia because it was known as the "sleep hormone." Unfortunately, it did not work well as a supplement to improve sleep. Recently, researchers found the cause: the dosage had been incorrect. When people over age 50 with age-related insomnia received 0.1-milligram, 0.3-milligram, or 3.0-milligram doses of melatonin half-an-hour before bedtime, a significant increase in sleep efficiency occurred with the 0.3-mg dose. The conclusion was that the lower dose had been too low and the higher dose had caused a feedback loop in the pineal.
Although rare, anomalies such as pineal tumors and pineal cysts do occur. Symptoms include fatigue, irritability, headaches, and nausea. While fatigue and irritability can look like a mood disorder, headaches or nausea are red flags for organic problems. University of California- San Diego researchers Namir Damluji and James Ferguson also have described a woman with a pineal tumor that presented with anorexia.
Mental symptoms of Hypopituitary
Loss of appetite
Medical Symptoms of Pituitary Disorders
Peripheral vision loss
|Low blood pressure|
|Body hair loss|
|Unintended weight loss or gain|
The pituitary has been called the master gland of the body because of its central role in governing homeostasis, maintaining the reproductive cycle, and directing the activity of other glands. Housed in the sphenoid bone at the base of the skull, it has important anatomic connections with the hypothalamus, visual pathways, cavernous sinus (a large collection of veins creating a cavity bordered by the temporal bone of the skull and the sphenoid bone, which is part of the eye socket) carotid artery, and cranial nerves.
The tiny gland originates from two discrete parts of the developing embryo: Rathke's pouch, a depression in the roof of the developing mouth, and the stomodeum, the precursor of the mouth and anterior lobe of the pituitary gland. The pituitary stalk forms the posterior lobe. The anterior, intermediate, and posterior lobes of the pituitary gland function as three separate endocrine organs, each characterized by distinct cell populations, secretory products, and regulatory mechanisms.
The anterior lobe secretes thyroid stimulating hormone, corticotropin, luteinizing hormone, follicle stimulating hormone, growth hormone, and prolactin. It is regulated by the hypothalamus via the portal vascular system. The anterior lobe comprises approximately 80 percent of the entire gland.
The posterior lobe releases oxytocin and vasopressin from axon terminals that originate in cell bodies located in the hypothalamus. Interestingly, the gland’s intermediate lobe is rudimentary in human beings, but produces several hormones whose physiologic significance has yet to be established.
Hypopituitarism can be caused by a tumor, an infection, a lesion, or a head injury. The pituitary sends messages to the adrenal glands, the thyroid, and other target organs. For this reason, damage to the pituitary often looks like a thyroid or adrenal gland problem. Hypopituitarism is often diagnosed as depression, a personality disorder, or anorexia.
Research from Duke University Medical Center and the U.S. Food and Drug Administration (FDA) suggests a link between pituitary tumors and antipsychotic medication drugs used to treat schizophrenia, psychosis, paranoia, and manic-depressive disorders. The connection has been suspected for over 20 years, but this is the first study that links the most widely used antipsychotic medication, risperidone (trade name Risperdal®), to pituitary tumors in humans. What is striking is that the drug was linked to 70 percent of pituitary tumors reported to the FDA's Adverse Events Reporting System database.
The findings were published in the June 2, 2006 issue of Pharmacotherapy by coauthors Ana Szarfman, Joseph Tonning and Jonathan Levine, all affiliated with the FDA. The researchers cautioned that the study, although suggestive, does not prove that the medications actually cause pituitary tumors.
“There are about eleven million people in the United States and Canada who have an overactive or underactive thyroid, two million of whom do not realize that they are sick.”
Lawrence C. Wood, MD, FACP President, Thyroid Foundation of America
Drugs that may produce hypothyroidism
Interferon-alfa (Alferon N, Intron A, Roferon A)
Lithium (Eskalith, Lithobid)
|Potassium iodide, KI (Pima, SSKI)|
Put your hand on your neck (as if you were pretending to choke yourself), and you will feel your Adam’s apple, which is blanketed by your thyroid gland. This butterfly-shaped gland, wrapped against the windpipe, is the largest pure endocrine gland in the human body; it measures approximately two inches across.
It is also the first gland to appear in the fetus. A baby's thyroid will begin to function at about 10 to 12 weeks of pregnancy. Thyroid hormones play an important role in the development of fetal nervous systems. They are likely derived from both the baby's thyroid gland, as well as the mother's thyroid hormones which cross the placenta.
It is known that iodine from a mother's diet also crosses the placenta and is used by the fetal thyroid gland to make thyroid hormone. Fetal iodine deficiency can cause newborn hypothyroidism or mental retardation (cretinism) and is a major world health problem in underdeveloped countries. However, in the United States, there is an abundance of iodine in the diet and disorders caused by a lack of iodine rarely occur.
The Human Thyroid gland produces T4 (Thyroxine), T3 (Triiodothyronine), small levels of T2, T1, and another important hormone called calcitonin. Calcitonin regulates calcium, and helps stop the leeching of calcium from bones. These hormones are released into the blood. Curiously, we still do not know what T1 and T2 actually do, although some research suggests that T2 may play a role in conversion of T4 to T3. T2 also increases the metabolism of the liver, heart, and muscle tissue. It also reduces brown fat. Because of this, T2 is becoming a popular tool for weight loss and bodybuilding, despite a lack of accreditation by the FDA.
The level of the gland’s activity is governed by thyroid stimulating hormone (TSH). The secretion of TSH is regulated by circulating levels of thyroid hormones via a negative-feedback loop and hypothalamic thyrotropin-releasing hormone (TRH).
In postmenopausal women, the incidence of thyroid disease is about 2.4 percent, but subclinical thyroid disease is about 23.2 percent. In those with subclinical disease, hypothyroid is 73.8 percent while hyperthyroid is 26.2 percent. Synthroid, used to treat hypothyroidism, is now one of the top five prescribed drugs in the U.S.
In 1974, diagnosing according to symptoms was put aside in favor of getting a diagnosis from lab results. At that time, the mainstream medical industry decided that TSH testing would be the gold standard for diagnosing hypo- and hyperthyroidism.
This has become a problem in that TSH levels are not a reliable indicator of thyroid function. As a consequence of relying on labs and not symptoms, many people today suffer for years with symptoms of thyroid problems.
Seasonal changes in light and temperature may affect the metabolism of brain thyroid hormones. T3 may itself be a neurotransmitter and may have an antidepressant effect. It enhances the effects of norepinephrine, serotonin, and γ-aminobutyric acid.
Malfunction of the thyroid gland can cause significant problems in the central nervous system. Although overt thyroid disease is rare among depressed patients, depression often co-exists with subclinical thyroiditis, suggesting that depression may alter the immune system, or could be an autoimmune disorder itself.
Stimulation of thyroid hormones often originates in an area of the brain called the hypothalamus, located in the brain just above the pituitary gland. When the hypothalamus secretes thyrotropin-releasing hormone, it triggers the pituitary gland to release thyroid-stimulating hormone (TSH).
In healthy people, almost all thyroxine is converted to triiodothyronine in the tissues. This means that the primary thyroid hormone finally delivered to and acting on tissues is T3. In normal health, maintenance of resting metabolism and excitability of membranes require between 35-50 micrograms of T3 a day.
Many environmental toxins deregulate hormones, but the thyroid is especially susceptible. This is of great concern because the thyroid is instrumental in orchestrating fetal brain development, including the processes of neural migration and myelination.
Thyroid problems are often missed, even after a complete physical. In my workshops and seminars, I have listened to several hundred people – mostly women – describe how they suffered from thyroid problems for years. The sufferers begin by going to a doctor complaining of sleep problems, lassitude, lethargy, malaise, and aches and pains. They may also have cognitive and memory problems. Hearing these woes, the doctor will conduct a physical and may request a thyroid panel. The panel comes back normal. This gets them a diagnosis of depression, and either an antidepressant, or a referral to a mental health professional. Neither psychotherapy nor psychotropics help the problems. The problem is labeled treatment resistant depression. After this, a journey of doctor-shopping begins.
After many doctors, many therapies, and numerous thyroid panels, a practitioner final says, “Mrs. Stevens, your thyroid panel looks good, but you look awful. Let’s try some thyroid anyway and see what happens.” What happens is almost complete remission of all symptoms. (Interestingly, the clinician that prescribes this treatment is often not an MD, but an OD, ND, or Nurse Practitioner.)
Thyroid panels can be very useful, but they rely on norms. Every person is different; what is normal for me may not be adequate for you.
Around 1974, TSH was declared the best test to diagnose hypothyroidism and hyperthyroidism, and to determine the amount of medication needed. This was apparently done without any clinical testing to see if TSH lab test results actually correlated with symptoms. During this time, diagnosing by symptoms was considered less useful than lab values.
Research reveals that people with thyroid disorders have significantly higher rates of panic disorder, phobias, irritability, obsessive-compulsive disorder, major depressive disorder, bipolar disorder and cyclothymia.
Researcher and clinician Leslie M.C. Goldenberg says that thyroid problems are routinely missed in older women because of bone thinning. Bone modeling causes the head to become positioned forward, bringing the lower part of the neck forward and down, causing the structures in the neck including the thyroid, to descend or crawl into the chest, often behind the breast bone. This means that it is often difficult or impossible for physicians to examine physically the thyroid of most older women.
According to Goldberg, hypothyroidism presents signs in old people which almost never appear in young patients. These are abnormalities in the cerebellum at the back of the brain which lead to an ataxic or drunken gait, aches and pains that are not in or around the joints, and carpal tunnel syndrome, a compression of an important nerve in the wrist, which results in tingling sensations.
Mental Symptoms of Hyperthyroidism
Marked anxiety and tension
Irritability and impatience
Exaggerated sensitivity to noise
Physical Symptoms of Hyperthyroidism
Increased body temperature
Intolerance to heat
|Increased bowel movements|
|Light or absent mentrual periods|
|Warm, moist skin|
The thyroid gland secretes hormones that control metabolism – the speed at which the body converts food into energy. Overactivity of the thyroid gland is called hyperthyroidism. Hyperthyroidism is the state of having low levels of TSH, high T4, and high T3. About 300,000 new cases of hyperthyroidism occur in the United States each year.
A significant number of patients will be initially seen by mental health professionals. A majority of hyperthyroid patients will show mild mental symptoms, but some will exhibit psychosis, hypo-manic or bipolar symptoms, dementia, confusion, depression, apathy, problems falling asleep, problems with concentration, hyperactivity, and anxiety.
Researchers estimate that 60 to 75 percent of people with hyperthyroidism will experience anxiety. In fact, the symptom array is often indistinguishable from anxiety disorders, presenting with restlessness, irritability, attention deficit disorder, poor concentration, and histrionic affect. Other symptoms include flight of ideas, pressured speech, irritability, short temper, and tangential speech.
The red flag for hyperthyroidism is weight loss.
The term autoimmune thyroid disease encompasses all of the autoimmune thyroid conditions, including Hashimoto's thyroiditis, Grave's Disease, most cases of silent thyroiditis, and postpartum thyroiditis.
Mental Symptoms of Hashimoto's thyroiditis
Lability of mood
Withdrawal from normal duties
|Difficulty with learning|
Physical symptoms of Hashimoto's thyroiditis
Dry, brittle hair and nails
Dry, itchy skin
Hashimoto's Thyroiditis is the most common cause of hypothyroidism in the United States. It is named after the first doctor who described this condition – Dr. Hakaru Hashimoto – in 1912.
Hashimoto's, also called autoimmune thyroiditis, is a condition caused by inflammation of the thyroid gland. It is an autoimmune disease, which attacks the thyroid gland as if it was foreign tissue. The cause is unknown, but the disease tends to occur in families, and is often associated with other autoimmune conditions such as Type 1 diabetes and celiac disease. Currently, it affects approximately 14 million Americans and is about seven times more common in women than in men. It most often presents in adulthood. There is a higher prevalence of chronic Hashimoto's Thyroiditis in children and adolescents with vitiligo. For this reason, researchers suggest that all children with vitiligo be assessed for thyroid disease.
Blood drawn from patients with Hashimoto's Thyroiditis will show an increased number of antibodies to the enzyme thyroid peroxidase, an enzyme found in the thyroid gland.
The antibodies' interaction with the enzyme causes inflammation in the thyroid gland. Eventually the thyroid gland is destroyed and the patient is rendered hypothyroid.
Like many thyroid maladies, Hashimoto's can present as a mental disorder, with bouts of excessive sleepiness, chronic fatigue, and depression.
Mental signs of Graves' Disease
Physical symptoms of Graves' Disease
Frequent bowel movements
Menstrual irregularities in women
It was 1835, when the Irish doctor Robert James Graves first described a case of goiter with bulging eyes, now called Graves’ Disease. Graves’ is now known to be an autoimmune disorder. It is the most common cause of hyperthyroidism. More than 90 percent of patients with Graves’ Disease have a malfunction in the immune system which releases abnormal antibodies that mimic TSH.
Mental symptoms include depression and anxiety disorders and, sometimes, cognitive dysfunction. Interestingly, a significant number of people have an altered mental state even after successful treatment of the hyperthyroidism. Anxiety, hypomania, and irritability are common symptoms prior to the diagnosis and, therefore, the person will be diagnosed with a mental disorder before the discovery of Graves’ pathology. Psychiatrist Paul Steinberg in 1994 published a case of a man diagnosed with paranoid disorder that eventually was associated with Graves’ Disease. Another study revealed that nine of thirteen subjects with Graves’ had major depression, eight of the thirteen had generalized anxiety disorder, and three were hypomanic.
Even with treatment, the condition is prone to relapse or worsen in the postpartum period. When this occurs, antithyroid drugs are started or their dose increased. Radioactive iodine can be given if the mother is not breast-feeding.
A 1993 article in the Journal of the American Medical Association, suggested that smokers are twice as likely as non-smokers to develop Graves’ Disease. Smoking or second hand smoke also worsens eye problems in people with Graves’ Disease.
Depression often co-exists with autoimmune subclinical thyroiditis, suggesting that depression may cause alterations in the immune system. Some clinicians posit that depression itself could be an autoimmune disorder. The outcome of treatment and the course of depression may be related to thyroid status as well. Adding thyroid hormones, usually T3 to antidepressant therapy is a well-documented treatment option for refractory depressed patients.
Hyperthyroidism is seven times more frequent in women. It also runs in families. Anxiety disorders and depression also presents more commonly and women. It has also been found that hyperthyroidism is more frequent among African-American women than is Caucasian women.
Mental Symptoms of Subclinical Hyperthyroid
A mild form of hyperthyroidism very common in the general population, particularly in women, is called subclinical hyperthyroidism. One of the more common causes of this disorder is repeated viral infections. Other medical problems frequently occur in people with subclinical hyperthyroidism, including cardiac abnormalities and bone loss.
An interesting finding in hyperthyroidism is a connection with carpal tunnel syndrome. Researchers have found that treating the thyroid problem often removed the need for carpal tunnel surgery.
The disorder often presents as a lump in the throat or a feeling of being strangled. This is often missed or misdiagnosed as hysteria.
Subclinical hyperthyroidism is usually referred to as a state where in the patient does not show the symptoms of hyperthyroidism. It occurs in more than 10 percent of women older than 60 years. The only abnormality is an increased level of TSH in their blood. This means that the pituitary gland is over-working to preserve the circulation level of thyroid hormones. Amiodarone and lithium are medications that are the less common causes of hyperthyroidism. Lithium carbonate, widely used in the treatment of bipolar patients, is well known to induce this malady.
Subclinical hyperthyroidism is defined as a normal serum free thyroxine (T4) and free triiodothyronine (T3) levels with a thyroid-stimulating hormone (TSH) level suppressed below the normal range, but usually undetectable. It is an increasingly recognized disorder. The problem with diagnosis is the measurement of only total T4 and T3 levels is often insufficient. T4 and T3 levels are often within the normal range; however, free T4 and T3 are increased. Most elderly patients with subclinical hyperthyroidism have a multinodular goiter, but other conditions such as Graves’ Disease or Hashimoto’s disease may also result in the problem.
This state may development into major depressive disorder. Even when hyperthyroid had been treated, researchers Martin Bommer and associates have found that many patients with subclinical or remitted hyperthyroidism showed more abnormalities than the controls in all dimensions investigated. Forty-three percent of these patients (compared to ten percent of controls) complained of seriously reduced well-being, feelings of fear, anxiety, hostility, and cognitive problems.
Treatment is often a low-dose of the drug methimazole (Tapazole) 5 mg per day, which may result in normal TSH levels. Unfortunately this medication can also cause upset stomach, nausea, loss of taste sensation, headache, drowsiness or dizziness.
“These quiet, disinterested patients, who look old for their age but do not look extremely ill, may quietly and peacefully sink into apathy, from that into coma, and die an absolutely relaxed death.”
F H. Lahey, 1931
Mental signs of apathetic hyperthyroidism
Medical signs of apathetic hyperthyroidism
Poverty of speech
Although hyperthyroidism usually presents as anxiety and restlessness, some will exhibit severe signs of depression, extreme apathy, and social withdrawal – a condition called apathetic hyperthyroidism. This presentation occurs more in elder adults, but may be seen in children, adolescents, and younger adults.
Because of the symptom array, it is often diagnosed as a mood disorder. Children and adolescents with the disorder may become withdrawn, appear disinterested, and have poor school performance. They may exhibit excessive sleep and weight loss. Most people with this condition will display no symptoms of thyroid problems. In some cases the person will have normal thyroid hormone levels.
A significant number of people with hyperthyroidism will eventually suffer from hypothyroidism, which may occur from five to twenty years after the first symptoms appear.
Hypothyroidism lowers metabolic rate. It also lowers body temperature. People with hypothyroidism exhibit psychomotor retardation, lethargy, fatigue and lassitude. Thyroxine (T4) stimulates metabolic activity in the body. Iodine is needed for proper thyroid function people who do not have enough dietary iodine may develop a goiter, which is a swelling of the thyroid gland. This results in under-activity of the thyroid, a condition called hypothyroidism. This disorder often present in psychological symptoms. Presentation of hypothyroidism is the state of having high levels TSH, low T4, and low T3.
Despite the known effects of thyroid on depression, reviews of the literature find little conclusive data about how thyroid function contributes to depression. While it is clear that not all people suffering from depression have overt thyroid dysfunction, it is also clear that a subgroup of depressed patients manifest subtle thyroid abnormalities which do not fit the criteria for thyroid problems. In many cases, the presence of a subtle thyroid dysfunction is ignored. This will oftentimes be labeled treatment resistant depression.
Smokers are more likely to have thyroid enlargement. Mild thyroid enlargement in smokers could be a sign of thyroid disturbance. Tobacco contains cyanide, which in the body is converted to thiocyanate, which acts as an anti-thyroid agent, directly inhibiting iodide uptake and hormone synthesis. Researchers believe that there are many other components of smoke that may have antithyroid action – decreasing the binding of triiodothyronine to its receptors or its post-receptor actions in the liver, muscle, or other organs, or both.
Symptoms of Central Hypothyroidism
|Intolerance for cold|
Central hypothyroidism is the decline in thyroid hormone because of inadequate stimulation of a normal thyroid gland by thyroid stimulating hormone. It is sometimes caused by pituitary disease or dysfunction of the hypothalamus. Causes include hypothalamic and pituitary tumors, Sheehan's Syndrome (damage occurs to the pituitary gland caused by severe blood loss during or after childbirth), sarcoidosis (an inflammatory disorder), histiocytosis (an abnormal increase in the number of immune cells called histiocytes), and lymphocytic hypophysitis (a rare inflammatory condition affecting the pituitary gland).
Central Hypothyroidism is common in patients who have been irradiated for pituitary tumors, sinus tumors, and brain tumors. The longer the interval since irradiation, the more likely a patient develops hypothyroidism.
Many people with this disorder show normal levels of TSH. Researchers posit that the TSH is modified and not functioning correctly; therefore, a TSH tests will not show abnormalities.
Symptoms of Subclinical Hypothyroidism
Treatment resistant depression
Alterations in cognition
Subclinical hypothyroidism is defined as a serum TSH concentration above the statistically defined upper limit of the reference range when serum free T4 (FT4) concentration is within its reference range.
In patients with subclinical hypothyroidism, lab tests show normal levels of serum free T4 and T3, but elevated serum TSH. The incidence of the disorder is from five to ten percent of the population, mainly in women. It most often occurs in women older than 45 years of age. The incidence in that population is 15-20 percent.
Between eight to fourteen percent of patients with subclinical hypothyroidism will have symptoms of depression, but they may have mild or no classic symptoms of thyroid hormone deficiency.
Pregnancy produces an increased demand on the thyroid gland. Toward the end of the first trimester of pregnancy, blood levels of TSH often are suppressed. The thyroid-stimulating activity of human chorionic gonadotropin (hCG) will cause some women to exhibit a transient hyperthyroidism. In normal individuals, this will not cause a significant load to the thyroid gland, but in females with subclinical hypothyroidism, the extra demands of pregnancy may cause a clinical thyroid disease.
Lifetime frequency of depression is significantly higher in people who meet the criteria for subclinical hypothyroidism.
"The prevalence of undiagnosed thyroid disease in the United States is shockingly high.”
Hossein Gharib, MD
Medical symptoms of thyroid problems
Although thyroid disorders often present as psychological problems, symptoms usually include observable medical problems such as diarrhea, protruding puffy eyes, and weight loss.
Any person with a mood disorder should be asked whether they have had a personal or family history of thyroid problems, as well as any previous treatment for thyroid problems.
Thyroid disorders are usually diagnosed with blood tests called thyroid panels. This is currently the most effective diagnostic tool. Be aware however, that some people with thyroid problems will present with normal lab values. In these cases, patients may have a history of doctor shopping, as the diagnosis is missed. For example, T4 levels are high in approximately 90 percent of hyperthyroid patients and low in approximately 85 percent of hypothyroid patients. This also means that 10 percent to 15 percent of people with thyroid problems will be misdiagnosed.
In 2003, the TSH diagnostic levels set by the American Association of Clinical Endocrinologists were changed from 0.4–6.0 to 0.3-3.0. The new improved range increased the number of Americans diagnosed with thyroid illness from 13 million to approximately 27 million. Unfortunately, over 13 million Americans with thyroid disease will remain undiagnosed.
Some labs and some practitioners may not be aware of the revised guidelines. These values are averages. Values may vary somewhat from lab-to-lab. Be sure to ask what the normal ranges are for each lab that is used.
Laboratory Values for Thyroid Disorders
Thyroid Stimulating Hormone
TSH under 0.3 indicates possible hyperthyroidism
TSH Over 3.0 is considered indicative of hypothyroidism
Total T4 test
4.5 to 12.5
T4 level less than 4.5 is an indication of an underactive thyroid when TSH is also elevated
T4 over 12.5 indicates hyperthyroidism
Low T4 with low TSH suggests a pituitary problem
Free T4 test
Free Thyroxine - FT4
|0.7 to 2.0||T4 lower than 0.7 is indicative of possible hypothyroidism|
80 to 220
Less than 80 can indicate hypothyroidism
These are general values or averages. Lab values may vary somewhat from lab to lab.
Unfortunately, the results reflected in the table above can do no more than indicate the possibility of a thyroid problem. Since a significant proportion of people who suffer from thyroid problems may have normal lab results, this means the results are unreliable and often produce a wrong diagnosis. In my seminars throughout the U.S., I have heard numerous stories about people doctor-shopping with symptoms of depression, sleep disturbances, cognitive problems, and chronic fatigue. Once thyroid panels show normal values, the thyroid is often discarded as a diagnosis. The person then visits numerous doctors and therapists for treatment of depression. After repeated treatment failures, they are labeled "treatment resistant."
“Doctors must treat the patient, NOT the blood test.”
Leonard Wartofsky, MD
True hyper- and hypothyroidism disorders are not mental illnesses, and therefore should not be treated with psychotherapy or psychotropics. In fact, psychotropics may cause adverse reactions in these disorders. Research states that hyperthyroidism should also not be treated with tricyclic antidepressants. Lithium and antipsychotics are also contraindicated.
I am not by any means suggested that you give medical advice to client or patients. Thyroid disorders are medical disorders that can be treated with medications, surgeries, or dietary alterations, which are clearly outside of psychotherapists’ scope of practice. Nevertheless, you should be aware of clinical treatments.
The goal of medical treatment is to restore normal levels of TSH. Medications are available for T3 and T4. But the thyroid hormones T2 and T1 are only in desiccated thyroid, which is natural thyroid hormone derived from pig thyroids. Very little is known about these hormones.
Some clinicians recommend the use of Armour thyroid, because it is a bio-identical hormone replacement and contains T1, T2, T3, T4, and TSH. Armour is the most well known of the natural desiccated porcine thyroid meds and oldest on the market, having been introduced in the 20th century. Other brands include Erfa’s Thyroid from Canada, and Naturethroid and Westhroid, which are both produced by RLC Labs. Another desiccated thyroid called Thyroid-S is imported from Thailand. Australia uses compounded desiccated thyroid powder. All come from pig thyroids and all use thyroid desiccated powder, which meets the stringent guidelines of the U.S. Pharmacopeia. Armour appears to be grandfathered in by the FDA, since it was around before 1938 when the FDA was created.
Although most thyroid patients do well with T4 medication alone, or on T4 and T3 together, a number of patients who do not respond to these drugs and switch to desiccated thyroid will find that their health improves. Some clinicians believe this is an indication that T1 and T2 may also have some function.
Although you can feel your thyroid by placing your hand on your throat, you cannot feel the four small nodules behind it, called the parathyroid glands.
The prefix para technically means beside, near, or alongside, but the glands are actually located behind the thyroid. Even though the words thyroid and parathyroid sound similar, the glands themselves are not related to one another and have completely separate functions.
A healthy parathyroid gland is usually about the size of a grain of rice. It is made up of about 80,000 very small parathyroid cells. Throughout the day, these cells measure the calcium in the blood.
Parathyroid glands secrete a substance called parathyroid hormone. It is the master regulator of calcium and phosphorus concentration in our extra-cellular fluids. When the calcium is low, they make parathyroid hormone (called PTH). When the calcium is high, they stop making hormone.
Parathyroid hormone's major target cells in the bones and kidneys, but malfunction in this gland can have profound effects in the central nervous system. About 25 per cent of people with idiopathic hypoparathyroidism will have mental problems.
Mental symptoms of hypoparathyroidism
Mild personality changes
Hypoparathyroidism is a condition in which the parathyroid glands do not produce enough parathyroid hormone, which eventually leads to a decrease in calcium in the blood, a condition called hypocalcemia. Hypocalcemia occurs rarely in adults, but is found more frequently in children and the elderly. It is more common in females that it is in males.
The two most common causes of parathyroid malfunction are thyroid gland surgeries that inadvertently damaged the parathyroids, or a vitamin D deficiency, which is often caused by nutritional deficiency or a kidney malfunction. This state can cause seizures, often with convulsions, frequent headaches, thinning hair, muscle weakness and muscle cramps, and numbness or tingling in the face of hands.
These physical symptoms do not look like mental illness, but they usually do not occur in the beginning stages of the problem. Instead, this disorder is emerges as depression or anxiety. When misdiagnosed, the disease progresses until physical symptoms eventually occur.
Mental symptoms of hyperparathyroidism
|Decreased ability to complete tasks|
Decreased sex drive
|Inability to concentrate|
Physical symptoms of hyperparathyroidism
|Tired all day|
Hyperparathyroidism occurs when one of the four parathyroid glands grows into a benign tumor. This causes the gland to constantly make large amounts of parathyroid hormone, without paying attention to how high the blood calcium is.
This disorder occurs in two forms: primary and secondary. Primary hyperparathyroidism is caused by parathyroid gland disease. This is most commonly due to a benign parathyroid tumor (called an adenoma) in one of the four parathyroid glands, which over-secretes the hormone. Women are four times likely to have hyperparathyroidism than men.
In most cases of hyperparathyroidism disease, one of the parathyroid glands has grown into a tumor usually not more than the size of an olive.
But this small tumor can cause significant mental symptoms including delirium, sudden onset dementia, depression, anxiety, psychosis, visual hallucinations, paranoid delusions and apathy.
Parathyroid tumors are often removed surgically. After surgical removal of a parathyroid tumor, low levels of magnesium may occur (the medical term for this problem is hypomagnesemia).
Primary hyperparathyroidism is a common disorder in people over 65 years of age. In this age group, the prevalence is three percent for women and one percent for men. Parathyroid glands stabilize calcium. The physical signs of this disorder are chronic elevations of blood calcium concentration (called hypercalcemia), kidney stones, and the decalcification of bones. Be aware, however, that even mild elevation of calcium may cause significant symptoms in some people. This subtle elevation is sometimes ignored by physicians and, therefore, the disorder will go undiagnosed. Experts in the science of parathyroid problems are quick to point out that the level of the calcium does not correlate with the amount or severity of symptoms a patient may experience. Because of the symptoms, this disorder is often diagnosed as depression. Because of the small increase in calcium, most doctors will not diagnose it as hyperparathyroidism. It is not uncommon for a person to suffer for several years before receiving an accurate diagnosis.
Although most cases are caused by only one parathyroid gland, about three-to-five percent of all patients with primary hyperparathyroidism will have an enlargement of all four parathyroid glands, a term called parathyroid hyperplasia.
Secondary hyperparathyroidism is caused by conditions outside of the parathyroid glands, which also leads to excessive secretion of parathyroid hormone. A common cause of this disorder is kidney disease. When the kidneys are unable to reabsorb calcium, calcium levels in the blood will fall, which then signal the parathyroid to secrete more parathyroid hormone to increase blood calcium. The condition may also be caused by inadequate nutrition, especially from diets that are deficient in calcium or vitamin D. It can also be triggered by diets that contain high amounts of phosphorus such as high protein, low carbohydrate diets. Lithium, frequently used for bipolar disorders, can cause hypercalcaemia and sometimes will cause irreversible hyperparathyroidism. The prominent physical sign of secondary hyperparathyroidism is decalcification of bone, leading to multiple fractures.
Physical symptoms of adrenal dysfunction
Lowered immune system
Inability to sleep restfully
Blood sugar imbalances
Put your hands on the lower back ribcage near your spine. Here, your hands are very close to your adrenal glands. They sit on top of your kidneys, are triangular shaped, and, when healthy, measure about one-half inch in height and three inches in length.
Each gland consists of the medulla, the center of the gland, and the cortex which surrounds the medulla.
Everyone is familiar with the term adrenalin rush, that feeling of euphoria and energy. Adrenalin is secreted by the medulla. It acts as a hormone and a neurotransmitter. In the medical world, adrenalin is also called epinephrine.
The adrenal cortex secretes other important hormones including cortisol, aldosterone, and the sex hormone androgen. Cortisol helps the body cope with stress, stabilizes blood sugar levels, modulates the immune system and helps control blood pressure. Aldosterone helps maintain the correct level of salt in the body, which also influences blood volume and blood pressure. Androgen is a male sex hormone that is responsible for male sexual characteristics. All of these hormones are synthesized from cholesterol. Particular enzymes are then needed to help convert cholesterol into the adrenal hormones.
Overexcretion of cortisol from the adrenal glands is often accompanied by depression. In fact, cortisol is elevated in 50 to 60 percent of depressed patients. Adrenal volume can sometimes be 70 percent larger in depressed people. Adrenal gland enlargement may be a measure of cumulative lifetime depression.
Chronic stress can cause the adrenal glands to malfunction. The most common clinical symptom of this condition is chronic fatigue; therefore, adrenal malfunction should always be ruled out when evaluating a person for chronic fatigue syndrome.
Other signs of weak adrenal function are overeating and weight gain, also conditions rife in our society.
When adrenals become completely nonfunctional, weight loss will often occur. Loss of salt from the kidneys will occur along with abnormally low blood pressure. This condition is most commonly seen in females.
Adrenoleukodystrophy is an inherited X-linked disorder that damages the adrenal cortex, testes, and the brain. It may occur at any age. Adult-onset disease often presents with mental problems. While the majority of patients have signs and symptoms typical of mania, psychosis and cognitive impairment may also occur. This disorder is under-recognized as a cause of psychiatric illness.
“The brain is a major target organ for corticosteroids.”
Joseph K Belanoffemail
“Cognitive deficits and elevated cortisol are hallmarks of depression.”
Mental symptoms of corticosteroids
Cortisol regulates many systems in the body, including maintaining salt and water balance, and regulating carbohydrate, fat, and protein metabolism. When a person becomes stressed, the pituitary gland begins to release adrenocorticotropic hormone (known as ACTH), which stimulates the adrenal glands to produce cortisol. The higher cortisol levels help the body cope with stress. Events that trigger this system include infections, physical trauma, and emotional problems. Healthy adrenal glands usually produce about 20 milligrams of cortisol per day, but when stress occurs it can produce five times as much.
Corticosteroids are drugs closely related to cortisol, a hormone that is naturally produced by the outer layer of the adrenal gland, called the adrenal cortex.
Physical symptoms of low DHEA
|Difficulty losing weight|
Dehydroepandrosterone (DHEA) and its related compound called DHEA sulfate (DHEAS) are the most abundant steroid hormones in the human body. Adult blood levels of DHEAS are 100−500 times higher than testosterone and 1,000−10,000 times higher than estradiol. Blood levels of these hormones peak around ages 25−30, and then begin a significant decline. By age 80, a person’s DHEA level is about 10 percent of what it was in his 30’s.
About half of the body's DHEA is produced in the adrenal cortex – with the rest coming from gonads, fat tissue, and the brain. Women are more prone to lower DHEA levels.
The pathway of steroid manufacture in the human body is:
Cholesterol – pregnenolone – DHEA – testosterone – estrogen
Adrenal insufficiency can cause low testosterone in men and women. It also causes a deficiency of DHEA. In a double-blind study of adrenal insufficiency in women, 82 percent of those taking 50 mg DHEA per day reported an improved sense of well-being, defined as better sleep, more energy, and better ability to handle stress. In addition, the subjects taking the supplement for four months showed significantly reduced anxiety and depression, and increases in energy. Increased sexuality was associated with androgenic effects. A 30 to 50 mg daily dose improved mood, sense of well-being, and sexual appetite in women with adrenal insufficiency. It’s important to note that the improvements were seen after four months, but not after one month.
DHEA is extracted from barbasco root, also called the wild Mexican yam. It is sold without prescription in the United States. Canada, however, has declared DHEA to be an anabolic steroid and it cannot be obtained without a prescription in that country.
Despite its popularity in the U.S. as a nutritional supplement, few clinical studies have been done on the efficacy of DHEA replacement therapy in humans. This may be, in part, because DHEA cannot be patented and, therefore, cannot be marketed as a pharmaceutical, so there is no monetary incentive to verify its usefulness. According to Dr. Marc Weksler at Cornell University Medical College, people with a family or personal history of tumors responsive to hormones, such as breast cancer or prostate cancer, should not use DHEA.
Mental symptoms of Cushing's Syndrome
Problems with concentration
Low sex drive
Cushing's Syndrome is over-activity in the adrenal glands. It is a state of chronic excess of cortisol. Cushing's Syndrome is usually caused by adrenal disease (which may result in adrenal tumors), but can also be caused by increased levels of ACTH secreted by the pituitary gland, or dysfunction in the hypothalamus.
Problems may also emerge from the use of corticosteroids. In these cases, a majority of people will show sporadic bouts of euphoria, increased appetite, hyper-sexuality, and increased activity level. Although the symptoms may look like a manic episode, most people with Cushing's Syndrome do not fit the criteria for bipolar disorder. In rare cases, however, the person may have bouts of manic psychosis.
Most people with Cushing's Syndrome initially present with psychological problems. Over 50 percent of people with this syndrome will have serious psychiatric problems including suicidal ideation, severe depression, or psychosis. In some cases, the person will exhibit significant agitation, emotional lability, and bouts of acute anxiety.
Although the majority of people suffering from Cushing's Syndrome will exhibit symptoms of depression, about 15 percent of people with this disorder may develop a psychosis or delusional disorder. The age of onset of this disease is typically somewhere between 20 and 60 years old.
As the disease emerges, physical symptoms arise, including hypertension, amenorrhea (the absence of menstrual periods in a woman of reproductive age), weight gain, muscle wasting, and obesity in the face, often called “moon face.” Surgery or radiation is needed for most patients with Cushing's disease due to adrenal tumors.
Mental symptoms of Addison's Disease
Poverty of thought
Medical symptoms of Addison's Disease
Low blood pressure
Darkening of the skin on parts of the body
Addison’s Disease is a hormonal disorder affecting about one in 100,000 people. It can occur in all age groups. It afflicts men and women equally. This disease can also come about as a result of the gradual decrease of production of the steroid hormones with aging. The disease occurs when the adrenal glands do not produce enough of the hormone cortisol, and in some cases, the hormone aldosterone. For this reason, the disease is sometimes called chronic adrenal insufficiency, or hypocortisolism. A common cause of Addison's Disease is an autoimmune response to the adrenal gland.
Similar symptoms make the differential Addison's Disease difficult at times: classic symptoms of Addison’s include vomiting, weight loss, hypotension, depressed mood, reduced drive, and increased irritability. All of these symptoms may also occur in anorexia nervosa. It also can present with chronic fatigue. Because the steady decrease in all the circulating corticosteroids is a slow and insidious process, this disorder is often initially diagnosed as a psychiatric problem.
The diagnosis of Addison's Disease is made by laboratory tests. If levels of cortisol are insufficient, X-ray exams of the adrenal and pituitary glands are also used.
Physical symptoms of pheochromocytoma
Chest and abdominal pain
In 1996, I worked with a woman who was severely anxious, depressed, and suicidal. Several years before, her father had committed suicide by shooting himself. She had two sisters that she described as alcoholic. All of them suffered from pheochromocytoma.
A pheochromocytoma is a tumor that occurs in the adrenal medulla percent of the time. In rare cases it may be found in the middle ear, carotid body (a small cluster of chemoreceptors and supporting cells located near the fork of the carotid artery), or the urinary bladder. Pheochromocytomas are often called "the great mimic” because of the vast array of symptoms. Most of these tumors emerge between 30 and 60 years of age, but they can occur at any time in the lifespan. About one in ten occur in children.
Seventy percent of people with a pheochromocytoma will never be diagnosed while alive; the disorder will be noticed in autopsy. Although it often presents as high blood pressure, many patients will suffer from restlessness and anxiety. The symptoms also mimic – and will be diagnosed as – panic attacks.
Mental symptoms of low testosterone in men
Reduced mental agility
By the age of 40, testosterone levels in men and women begin to decrease by about one percent a year. This progressive decline in testosterone increases the risk of obesity, heart attack, osteoporosis, and muscle loss. Low levels of testosterone can also cause decreases in sex drive and bone mineral density.
It is estimated that four million Americans suffer from low testosterone, yet about five percent of these are being treated. This low treatment level is caused simply because testosterone is seldom assessed in a routine physical.
Physical symptoms of low testosterone in men
|Decreased lean body mass|
Decreased body hair
Increased facial wrinkling
Mental symptoms of low testosterone in women
Reduced mental agility
In men, testosterone is produced mainly in the Leydig cells, found in the testes, but smaller amounts are manufactured in the adrenal glands. The normal level of testosterone in the bloodstream for men is between 350 and 1230 nanograms per deciliter. (A nanogram is one-billionth of a gram. A gram is about 1/30 of an ounce. A deciliter measures fluid volume that is 1/10 of a liter. A liter is a little bigger than a quart.) Low testosterone levels in men may present as depression but it can also cause problems with cognition, and increase violent behavior.
In women, testosterone is produced in the ovaries and adrenal glands. The ovaries continue to produce testosterone even after menopause. Healthy young women produce approximately 300 micrograms of testosterone per day, about half of which is derived from the ovaries, and half from the adrenal glands. For this reason, women who have their ovaries removed often experience a significant drop in testosterone.
In women after menopause, testosterone levels drop. In addition, estrogen replacement therapy often reduces testosterone levels, which may manifest as lack of energy and libido.
Testosterone deficiency in women may be caused by premature ovarian failure, removal of the ovaries, estrogen preparations, removal of one or both adrenal glands, adrenal disease, pituitary disease, HIV, Turner's syndrome, and high-dose corticosteroids. Simple aging and natural menopause may also contribute to testosterone deficiency in some women.
Testosterone levels affect couples' behavior. Research shows that when wives with high testosterone chose a problem to discuss, both parties are more negative than when the husband chose the topic. Husbands are more positive about problem solving and providing emotional support when both parties have similar testosterone levels. Studies from researcher Peter Gray show that testosterone begins to decline shortly after marriage, but surges upward when couples divorce.
Estrogens can be produced in the brain from steroid precursors. As an antioxidant, they have been found to have neuroprotective function. Estrogen lowers the level of monoamine oxidase (MAO). Low MAO means higher levels of serotonin. Therefore, low estrogen may cause irritability and depression. In these cases, estrogen therapy is usually effective.
Recently it has been discovered that women who take estrogen plus progestin have 10 to 30 percent higher risk of hearing loss. This combination also increases the risk of Alzheimer's. Estrogen alone decreases the risk of multiple sclerosis. In a recent study of women on chemotherapy who either stopped estrogen replacement therapy or started tamoxifen, 38 percent developed major depressive disorder, the majority within six months, and 95 percent exhibited dysphoria and/or insomnia.
During the reproductive years, most estradiol in women is produced by granulosa cells of the ovaries. Smaller amounts of estradiol are produced in the adrenal cortex in women and in the testes in men.
In both sexes, testosterone is converted to estradiol. Fat cells convert precursors to estradiol and will continue to do so even after menopause. Estradiol is also produced in the brain and in arterial walls. An Australian study in 2008 showed that women’s schizophrenia symptoms were significantly alleviated by adding estradiol skin patches to conventional antipsychotic therapy.
Physical symptoms of Tourette's Syndrome
|Sudden motor tics (body movements)|
Sudden vocal tics (sounds or words)
Tourette’s Syndrome is a common, hereditary neurological disorder often presenting with tics and a compulsive use of obscene words. However, it is sometimes manifested by aberrant sexual behaviors, including hypersexuality, exhibitionism, transvestitism, transsexualism, sadism, masochism, pedophilia, fetishism, aversion to being touched, and aversion to sex.
What mental health clinicians often miss is that Tourette’s Syndrome may present as attention deficit hyperactivity disorder, obsessive-compulsive behaviors, conduct disorder, oppositional defiant disorder, rages, mania, depression, anxiety, panic attacks, sleep disorders, and phobias.
The presentation of these behaviors often results in a referral to a psychotherapist. Although these behaviors are primarily neurological, they may be misinterpreted as parenting problems or family dynamic difficulties. The disorder was originally thought to be genetic, but most researchers now believe it is the result of a variety of genetic and environmental factors, not of any single specific gene.
There is a three to four times higher frequency of Tourette’s Syndrome in males than females. In patients with a typical onset, there may be a family history of tics or obsessive–compulsive disorder. About 50 percent of Tourette’s patients meet the criteria for attention deficit hyperactivity disorder. It is often the presenting problem. About one-third meet the criteria for obsessive-compulsive disorder or anxiety disorders. In adolescence, self-consciousness, social discomfort, and depressed mood frequently occur.
Tics occur in 10 to 20 percent of school-age children, whereas the prevalence of Tourette’s Syndrome is only about one in two thousand. However, this number may be low, since the diagnosis is based on clinical populations, not people in the general population with minimal tics. About one-third of children with Tourette’s Syndrome have learning disabilities resulting in the need to repeat a grade. In this study of children in special education, 26 percent had some form of tic disorder as compared to six percent in regular classroom students.
Researcher Simon Baron-Cohen believes that a majority of mild cases of the syndrome are never diagnosed. For example, tics may manifest themselves as difficulties with handwriting, which is usually not diagnosed as a disorder. As a result, some children with this disorder may have difficulty finishing their homework because they feel compelled to do it over and over until it is perfect. Although this may appear to be obsessive-compulsive disorder, it may instead be Tourette’s Syndrome.
Mental symptoms of multiple sclerosis
Physical symptom of multiple sclerosis
Visual field problems
|Tingling in hands and feet|
Multiple sclerosis (MS) is an inflammatory, autoimmune, demyelinating disease of the central nervous system that causes damage to the brain and spinal cord. MS tends to appear in colder climates, and rarely occurs in tropical areas of the world. Interestingly, no cases of multiple sclerosis have been reported between the latitudes of 40 degrees north and 40 degrees south. Therefore, the disease is found mainly in the northern United States and in the northern portion of other countries around the world. To give you a feel for where that line exists in the U.S., the 40th parallel marker is in White Cloud, Kansas, and Boulder Colorado's Baseline Road runs on the 40th parallel.
Curiously, when people who are born above the 40th parallel move to a tropical climate with their children, the children's risk of multiple sclerosis is very low, and conversely, when children move from a low risk to a high risk environment before they are 15 years of age they assume a higher risk of the disease.
Even more intriguing is that sporadic outbursts of MS that have occurred throughout history. The largest outburst occurred in the Faroe Islands (a group of islands located between Iceland and Norway at the 62nd parallel) after the occupation by the British troops in World War II.
Multiple Sclerosis is the most common demyelinating disease of the central nervous system, especially in young adults. The age of onset of MS is usually between 20 and 30 years. Seventy percent of sufferers will show symptoms somewhere between age 20 to 40. Although the malady rarely occurs prior to 10 or after 60 years, there have been recorded cases as early as age two and in people over 67. Females are affected more frequently than males.
There also appears to be a genetic susceptibility for the disorder. It is found primarily the people of German and Scandinavia descent, but is almost non-existent in Africans, African-Americans, Asians, and Asian-Americans, and is very rare in South America. For this reason, a history of family genetic origin, and geographic locations the person has lived in is diagnostically useful these cases.
Other evidence of genetic linkage is the finding that the incidence of MS in first degree relatives is 20 times higher than in general population, Identical twins have a concordance rate of 30 percent, while fraternal twins have concordance rate of less than five percent.
MS damages the myelin sheath, a fatty layer that insulates neurons in the brain and spinal cord. It acts as insulation the way plastic insulates an extension cord. When damage to this insulation occurs, pathways in the brain short-circuit, causing physical and mental symptoms. The cause of multiple sclerosis is unknown, but many researchers believe it is an autoimmune disorder provoked by toxins.
Although the disease may manifest itself in many ways, it usually causes damage in the cerebellum, the spinal cord, and the optic nerves. However, MS can manifest as a neuropsychiatric disturbance even in the absence of physical disabilities. A good proportion of people suffer from with Multiple Sclerosis will present a psychological problems first, which will get them a psychiatric diagnoses. Here is a case study from researcher Diane Treadwell-Deering and associates:
"A 14-year-old Hispanic boy with a six-month history of a psychotic disorder necessitating several hospitalizations who was incidentally found to have multiple sclerosis with no physical findings. Neuropsychological assessment revealed impairments in word finding, bilateral fine motor skills, and attention. Imaging and laboratory studies have supported the diagnosis of multiple sclerosis. Steroid and immunomodulating therapy has not significantly affected psychiatric symptoms. He had poor response to psychotropic medications as well."
MS often presents with unusual symptoms, such as, dysphasia, dysgraphia, and dyslexia. Others will suffer chronic fatigue, pain, depression, suicidal ideation, and cognitive dysfunction. In some cases in the early stage of MS, people will experience bouts of euphoria, which is sometimes misdiagnosed as bipolar disorder. Another symptom of the disorder is hypersexuality, which may be diagnosed as histrionic personality disorder.
Look for any unexplained neurological findings. For example, subtle motor problems, such as clumsiness or tingling in the hands and feet often occur with Multiple Sclerosis. A neurological workup, including an MRI, is needed for a diagnosis. A blood test for MS called gMS™ can also predict clinical syndromes suggestive of MS.
A nonblinded biochemical dietary experiment on MS patients showed that all abnormalities could be normalized by daily intake of selenium, vitamin E, and vitamin C. Dr. Paolo Zamboni believes that 90 percent of people with MS have a malformation or blockage in the veins that drain blood from the brain. His research suggests that a simple vascular surgery will cause significant improvement.
"The relation between migraine and major depression suggests a common neurobiology."
Gretchen Tietjen, MD
Mental symptoms of migraines
Physical symptoms of migraines
|Numbness in the hand and other parts of the body|
Every year there is a worldwide migraine art competition. The artwork is a representation of the migrainers' visual hallucinations.
Migraine symptoms often include visual and auditory hallucinations, abnormalities in taste and smell, nausea, and dizziness. British novelist Hilary Mantel in her biography Giving Up the Ghost, describes her migraine experience:
“Sometimes the aura takes more trying forms. I will go deaf. The words I try to write end up as other words. I will suffer strange dreams, from which I wake with hallucinations of taste. ... A tune will lodge in my head like a tic and bring the words tripping in with it. … It’s a familiar complaint, to have tune you can’t get out of your head. But for most people the tunes aren’t the prelude to a day of hearty vomiting.”
A migraine headache is a vascular headache that usually occurs in one side of the brain and is progressively severe. A full-blown migraine is often a throbbing headache that impacts the occipital lobe and/or fronto-temporal brain regions – areas that are implicated in mood disorders.
Migraines affect about 15 percent of the population. They are significantly more common in women than in men. The headaches are frequently accompanied by nausea, vomiting, photophobia (an abnormal sensitivity to or intolerance of light), phonophobia (a heightened response to sound), and focal neurological deficits, sometimes presenting with numbness or paralysis.
International Headache Society divides migraines into two distinct categories: with aura or without aura. Migraines without aura are the most common, and affect about 80 percent with the condition, while migraine with aura occurs in the remaining 20 percent.
Migraine headaches significantly increase the risk of depression and fatigue. In a 2007 study, women with frequent migraines were four times more likely to report symptoms of major depression than those with infrequent, episodic headaches.
In some people intermittent numbness of a hand or one side of the body may occur. Because if the presentation, a complete workup should be done to rule out other neurological such as transient ischemic attacks (TIA), strokes, tumors, or seizure disorders.
About one-fifth of migraine sufferers have a medical condition called patent foramen ovale or PFO, which is a small hole in the heart. In certain patients, usually suffering with migraine with aura, surgical closure of the PFO reduces the frequency of migraine by about 50 percent.
Basilar migraine, an ischemic event on the basilar artery, often presents with vertigo, double vision, and other visual disturbances with no headache. Migraines with these symptoms referred to as vertebrobasilar migraines.
Many researchers now believe that many migraines are spawned because of deficits of mitochondrial metabolism. They find that 400 mg of riboflavin (vitamin B2) and/or alpha lipoic acid ameliorates the headaches. Botox has also been shown to decrease migraines.
"No head injury is too trivial to ignore."
Traumatic brain injury (TBI) is the injury or damage by a blow to head. A TBI can be a closed head injury in which the skull and brain remain intact, or a penetrating injury, where an external object penetrates the skull and brain. Researchers state that every fifteen seconds, someone in the United States suffers a traumatic brain injury.
On September 13, 1848, twenty four-year-old railroad worker, Phineas Gage, had an iron rod, known as a tamping iron, rammed through his head by an explosion. The bar entered the top of his head, passed through the frontal lobe, and exited through his the left cheek. Astonishingly, he did not lose consciousness. However, after the accident his demeanor was drastically changed. He was unable to work, and exhibited bizarre behavior. The bar and Gage’s skull are on display at Harvard University.
It seems clear that head injury would change brain function. However, mild head trauma is often overlooked as a cause of mental disorders. In fact, the significance of head injury and mental health is fraught with controversy. A significant proportion of head injury patients are thought to be malingering.
In 2002, researchers at the University of Pennsylvania Medical Center assessed the total brain atrophy in 14 patients with mild or moderate traumatic head injury three months after injury, and in seven patients at two time points more than three months apart. Whole-brain atrophy was found among mild or moderate traumatic brain injury sufferers. The atrophy became evident at an average of eleven months after the trauma. Injuries that caused loss of consciousness produced even more atrophy.
In another study at the University of Washington in Seattle, people with moderate to severe and mild brain injuries were associated with an increased risk of psychiatric illness. The authors stated that although moderate to severe injuries carried higher initial risk, mild injuries were often associated with persistent psychiatric illness. Ravi Kant at the Medical College of Pennsylvania has reported four individuals who developed OCD symptoms after a closed head injury.
Many people forget that they have had a mild head injury. Asking about getting hit on the head should be an integral part of a mental health assessment.
Symptoms of postconcussion syndrome
|Problems with social function|
A concussion is a mild traumatic brain injury that usually occurs after a blow to the head. A concussion can occur with or without loss of consciousness. In many cases, the person may experiences a brief lapse of memory or a feeling of being dazed.
Most people who experience a mild-to-moderate brain injury will experience symptoms of postconcussion syndrome. The symptoms usually appear within the first seven-to-ten days, and gradually decrease within three months. However, about 15 percent of those who suffer from a concussion will have symptoms lasting more than a year.
Physical symptoms of concussion include nausea, vertigo, insomnia, ringing in the ears, blurred vision, changes in appetite, and decreased sex drive. In some cases, there may be difficulty speaking or communicating. Sensory problems, such as hearing, smell, and taste issues, may also occur.
There has been a long-standing debate as to whether postconcussion syndrome is a psychological or neurological problem. Recently, however, post-mortem studies of concussion victims show diffuse, microscopic axonal injury, and brain scans show lesions in ten percent of individuals with concussions.
The risk of developing post-concussion syndrome increases with age. Concussion symptoms are reported more often in women, but some researchers believe that this is because women are more likely to seek medical help than men.
Researchers M.W. Collins and G.L. Iverson published a study of high school and college athletes who had suffered concussions. A total of 78 athletes sustaining sports-related concussion were selected from a larger sample of 139 concussed athletes. These subjects exhibited on-field presence of disorientation, posttraumatic amnesia, retrograde amnesia, and loss of consciousness.
A computerized neuropsychological test battery was administered pre-season and, on average, two days post-injury. Good post-injury presentation was defined as no measurable change, relative to baseline, in terms of both memory and symptom composite scores. Poor presentation was defined as a 10-point increase in symptom reporting and 10-point decrease in memory functioning.
The athletes demonstrating poor presentation at two days after the injury were more than ten times likely to have experienced retrograde amnesia following the injury when compared with athletes exhibiting good presentation. Similarly, athletes with poor presentation were over four times more likely to have exhibited posttraumatic amnesia and at least five minutes of mental status change. The authors found that it was the presence of amnesia, not the loss of consciousness, that predicted cognitive deficits following a concussion.
Soon after his car accident in 1932, classical composer Maurice Ravel became unable compose. Although many researchers contribute this to dementia, others believe it was the result of whiplash.
Whiplash is the most common type of injury following an automobile accident. It is one of the most common causes of litigation after an injury. The validity of mental health problems caused by whiplash is controversial. The most common complaint is depression.
A stroke is a life-threatening event in which the brain's oxygen supply is cut off, often causing brain damage. There are two basic types of stroke: a hemorrhagic stroke, when a blood vessel bursts and causes abnormal blood to flow into the brain, and an ischemic stroke, when a blockage of blood flow to brain tissue causes it to starve and die. Each year, more than half-a-million strokes occur in the United States.
Although the word "stroke" usually conjures images of paralysis, aphasia and apraxia, strokes may also cause cognitive, emotional, and behavioral problems, including bizarre mental syndromes.
Having a stroke can be a traumatic experience that will often cause prolonged mental problems. In 1998, the Royal Edinburgh Hospital in the UK found that six months after stroke, 26. percent of the patients met the DSM-5 criteria for an anxiety or depressive disorder – depression being the most common diagnosis. A 2015 research found 220,336 stroke patients with a total follow-up time of 860,713 person-years. During follow-up, there were 1,217 suicide attempts, of which 260 were fatal.
Transient ischemic attacks are strokes that last only a few minutes. For this reason, they generally do not cause permanent damage, but they are a critical warning. About 10 percent of strokes are preceded by TIAs. Researchers in the ongoing Northern Manhattan Stroke Study have shown an association between periodontal disease, a chronic low grade infection of the bone underlying the teeth and a thickening of carotid artery plaque, and a major risk of stroke.
A silent stroke is an event that is not seen as a stroke. There is no paralysis or other motor problems. Strokes of this nature are sometimes misdiagnosed as a mental illness.
The basilar artery is the large artery coming up through the spinal cord into the bottom of the brain. Symptoms of a basilar artery stroke are avolition, apathy, and dizziness. A common but unusual symptom is pathologic laughing or crying.
The insula, a structure found between the temporal lobe and the frontal lobe, is related to olfactory, gustatory, visceral, and limbic function. The posterior insula is related to auditory sensation, bodily sensations, and skeletomotor function. It also plays an important role in the experience of pain and mediates emotions, including disgust, anger, fear, empathy, happiness, and sadness. A stroke in this part of the brain can present with the attenuation or loss of these abilities, and often presents as a mental disorder. Interestingly, smokers who have a stroke in the insula stop smoking immediately.
Symptoms of brain tumors
|Unusual symptom array|
|No previous history of the presenting problem|
Brain tumors are relatively rare, comprising about 1.5 percent of all malignant tumors. Nevertheless, they are increasing rapidly. In 1997, eighteen thousand new brain tumors were diagnosed – a 50 percent increase from 1987. Data of tumor incidence in 2008 show that one in five thousand people over 60 will develop brain tumors.
Researchers from the National Institute on Aging in Bethesda Maryland have found a significant increase in brain tumors in people over the age of 75. The incidence of the tumors has doubled from 1968 to 1985 (which was the last year for which statistics were available). For those over 80, the rate of increase was 300 percent, which is an increase of 23 percent per year.
While the causes of brain tumors are usually unknown, researchers believe that many are caused by toxins. For example, high levels of brain tumors occur in people working in oil refining, rubber manufacturing, and drug manufacturing industries. Tumors can also be triggered by viral infections and exposure to radiation. One type of radiation that has been suggested as causing tumors is the cell phone. Both cell phones and a household cordless phones use a form of microwave radiation to send and receive signals.
Tumors that originate in the brain are called primary tumors. But cancers from other parts of the body sometimes spread into the brain through a process called metastasis. These tumors are called secondary tumors. Although cancer from anywhere in the body can spread to the brain, secondary tumors occur most often with breast or lung cancers. If a tumor begins in the breast and spreads to the brain, the cells of the brain tumor will resemble abnormal breast cells, not abnormal brain cells.
Of concern for mental health practitioners is the finding that primary brain tumors occur 20 times more frequently in psychiatric patients than in the normal population. The rate of primary brain tumors in hospitalized psychiatric patients is one in one thousand.
One in one thousand people complaining of headache has a brain tumor, and 60 percent of people with brain tumors have headaches. Yet 50 percent of people with brain tumors will be misdiagnosed with a psychiatric problem. This is unfortunate, because the tumor will continue to grow unabated while the person goes from psychotherapist to psychotherapist.
Mental symptoms of frontal lobe tumors
|Confusion and disorientation|
|Socially inappropriate behavior|
|Hypo- or hyper-sexuality|
The frontal lobes of the human brain are the harbingers of judgment, foresight, motivation, social skills, and personality. They are also responsible for thought, attention, planning, reasoning, movement, sense of smell, and sexual urges.
A person with frontal lobe tumor can exhibit mood swings, decreased academic performance, unpredictable crying, unusual sexual behaviors, violent behavior, and suicidal ideation. Tumors in the right frontal lobe can present as excessive elation and euphoria, a non-critical perception of reality, lack of concentration, diminution perception, and a tendency to confabulate. They may also exhibit anosognosia, a condition in which a person who suffers disability will be unaware of the existence of his deficits.
Symptoms of tumors of the parietal lobe
|Difficulties with handwriting|
|Difficulty with math|
|Problems with movement|
|Loss of the sense of touch|
The parietal lobes are responsible for intellect, reasoning, sensation of touch, response to internal stimuli, portions of language and reading functions, and some visual functions.
Because the parietal lobe interprets various bodily sensations, there may be an altered awareness of pain, touch, temperature, pressure, shapes, sizes, and parts of the body. It may be hard to tell left from right or make comparisons.
The occipital lobe is primarily responsible for vision; therefore, tumors are likely to cause visual hallucinations. Loss of segments of visual field may also occur.
Mental symptoms of temporal lobe tumors
The temporal lobe is responsible for memory, behavior, hearing, emotions, and participation in visual pathways. Tumors in this area are often manifested as anxiety, panic attacks, and psychosis.
Tumors in the hypothalamus may cause emotional changes, changes in the perception of hot and cold, rage, mania, emotional lability, altered sexual behavior, and delusions involving complicated plots.
The cerebellum is a cauliflower-like organ at the back of the brain. It is responsible for monitoring sequential activity, including balance and coordination, and complex motor skills, including walking and talking. Cerebellar tumors may present as balance and gait disturbances.
The third part of the brain, the brainstem, connects the brain to the spinal cord. It controls some of the most important and necessary body functions, such as breathing and maintaining body temperature and blood pressure. It also controls hunger and thirst.
Symptoms of seizure disorders
|Sudden changes in behavior|
|Changes in sensory perception|
|Changes in mood|
|Unusual interpretations of the environment|
Changes in mood, behaviors, and emotions as a consequence of seizures have been recognized for centuries. Ancient texts, including the Bible, describe unusual thoughts, feelings, and behaviors cause by seizures.
A seizure is an episode of abnormal electrical activity in the brain. Although seizures are not part of normal brain function, many people actually experience epileptic like episodes frequently; a sudden jolt just prior to falling asleep is called a hypnagogic jerk. Other researchers believe that the experience of déjà vu may be caused by a transient seizure. Repetitive seizures are characteristic of a condition called epilepsy.
Seizures can be caused by lesions in the brain, head injuries, brain tumors, toxins (such as lead poisoning), abnormalities in brain structure, infections, and fevers, but in half of the people with seizures, no cause can be found. The types of symptoms seizures create are dependent on where electrical activity takes place in the brain. Other factors, such as the person's age or general state of health, may also be a factor in how seizures manifest themselves.
In some cases, uncontrolled seizures can, over time, cause brain damage that results in impairment of mental and physical abilities. It is well known that seizure disorders are more prevalent in people with neurological disorders, immune-system problems, and mental disorders.
Seizures are often classified as primary or secondary. A primary seizure is usually genetic or structural.
The secondary seizures, however, may be caused by prenatal events, or environmental toxins and brain pathologies, including brain tumors, vascular disease is, anoxia, heavy-metal poisoning, hypoglycemia, and high fevers. Seizures can also be caused by hypoparathyroidism.
Seizures are diagnosed by observation, neurological examinations, electroencephalogram (EEG), and brain imaging techniques.
As of 2008, the Center for Disease Control estimates that about 2.3 million Americans have seizure disorders. The prevalence rate is approximately one in one hundred-eighteen. Because the symptoms may manifest as perceptual changes, some people are not aware that they are having seizures.
Questions to ask:
Mental symptoms of temporal lobe seizures
|Anger and hostility|
|Hypergraphia (excessive writing)|
|Altered sexual interest|
|Sense of personal destiny|
|Viscosity (incessant talking)|
The prevalence of temporal lobe seizures is estimated to be three in one thousand. More than one third of people with these seizures will experience signs of mental problems as a result of these events.
A predominant number of people who have seizure activity in the temporal area will exhibit an array of symptoms called Geschwind Syndrome (also known as Waxman-Geschwind Syndrome or Gastaut-Geschwind Syndrome).
This syndrome usually presents with circumstantialities, excessive talking, chronic compulsive writing (hypergraphia), intensified mental life with deepened cognitive and emotional responses to certain events, hyper-religiosity, hyper-morality, and hyposexuality. A significant number are completely asexual. Many will interpret their symptoms as religious callings. Viscosity (incessant talking) is also correlated with seizure duration and left-handedness.
Geschwind Syndrome is usually associated with left-side temporal lobe seizures. Geschwind Syndrome has always caused controversy. Some believe that it represents a specific psychiatric disorder, while others assume temporal lobe epilepsy is a neurological condition, not a psychiatric condition. Geschwind Syndrome can be seen both in the inter-ictal (between seizures) and the ictal (during seizures) states. Some have come to call it Van Gogh's Malady. Most people with this syndrome do not seek mental help. They consider these phenomena normal.
Auditory seizures are caused by a seizure in the superior temporal gyrus. This procedure may manifest itself by ringing in the ears or buzzing or hissing sounds. These symptoms have sometimes been misdiagnosed as anxiety or hysteria. Sensory seizures are disconcerting to the person experiencing them. Because they do not understand what's happening to them, they may misinterpret their symptoms as a psychological disorder.
A seizure in the superior temporal gyrus may also cause bouts of vertigo, a phenomenon called a vertiginous sensory seizure. This may be experienced as dizziness or nausea and is sometimes misdiagnosed as a somatization disorder.
Frontal lobe seizures often occur during sleep. Signs of this can be bicycle pedaling motions and pelvic thrusting. Some people scream profanities. Uncontrollable laughing or crying may occur. The person may also awaken with the feeling of choking along with abnormal motor activity.
These seizures can be caused by tumors, vascular malformations in the brain, or head trauma. A rare genetic disorder called autosomal dominant nocturnal frontal lobe epilepsy is also known to cause these events. Having a parent with this form of seizure means a 50 percent chance of inheriting the gene.
Excessive daytime sleepiness may be a sign of nocturnal frontal lobe seizures, and may be misdiagnosed as obstructive sleep apnea.
Somatic sensory seizures occur in the post-central gyrus of the parietal lobe. Although many of these seizures result in convulsions, some do not. A significant number of people will be unaware that they have a seizure disorder, but will present with anxiety or depression. Right parietal lobe seizures can cause panic attacks.
Visual sensory seizures occur in the occipital lobe. They are usually characterized by unformed visual hallucinations. Often, these are flashing colors and provide problems with vision. These types of seizures may be misdiagnosed as an eye disorder, a migraine headache, or – in some cases – hysteria.
The anterior cingulate cortex is vital to cognitive functions such as conflict, self-regulation, decision-making, and emotions. Patients with anterior cingulate cortex seizures often display aberrant social behavior, psychopathic or sociopathic behaviors, tics, and obsessive-compulsive behavior.
Panic disorder research suggests that panic attacks are familial. Panic attacks in these families show that women have twice the frequently as men. Panic is not associated with an increased familial risk of other psychiatric conditions. Although most panic attacks appear to be primary mental disturbances, some evidence suggests a biological basis for panic disorder, possibly associated with temporal lobe dysfunction, including seizures.
In these cases, a full-night video-polysomnographic monitoring is needed to differentiate between the two conditions, and to verify, in the case of the co-existence of the two disorders, which is the one responsible for sleep disruption. Research demonstrated that obstructive sleep apnea can cause nocturnal panic attacks. A sleep assessment can accurately diagnose nocturnal panic disorders.
“Invariably, the hypoglycemic attack is characterized by some psychiatric phenomena and indeed the mental symptoms may dominate the clinical picture.”
Edwin J. Kepler MD
Mental symptoms of hypoglycemia
Physical symptoms of hypoglycemia
|Nausea and vomiting|
Hypoglycemia is a drop in blood glucose. Although many people with this problem may feel dizzy, weak, and shaky, others manifest mental problems such as hysteria, depression, anxiety, panic attacks, and psychosis. It is also misdiagnosed as a seizure disorder, brain tumor, narcolepsy, multiple sclerosis, as well as cardiac arrhythmia.
It can also look like stroke or a transient ischemic attack. There may be loss of limb movement which can be misdiagnosed as a conversion disorder.
There are three major causes of hypoglycemia – injections of insulin, organic pathologies, and unknown causes. Organic hypoglycemias can be endocrine-related, including problems in the pituitary, adrenal, or thyroid insufficiency. Changes in the pancreas may also occur. Autoimmune disorders , such as Lupus, Sjögren Syndrome, Hashimoto Thyroiditis, Addison’s Disease, rheumatoid arthritis, Type 1 diabetes, polymyositis (muscle inflammation), scleroderma (a connective tissue disorder), vitiligo (loss of skin pigment), and pernicious anemia (low B12 levels) also play a part in blood sugar stabilization. It is the unknown causes group that is most frequently diagnosed as mental illness.
Reactive hypoglycemia is the term for recurrent episodes of hypoglycemia occurring two to four hours after eating a high carbohydrate meal. The diagnosis for this state is a concentration of blood sugar 40 mg/100ml or less. Hypoglycemia may also occur following an injection of insulin. Symptoms include nervousness, hunger, weakness, vertigo, and faintness. Children with low blood sugar – especially children with Type 1 diabetes – have diminished levels of cognitive function. Many of these children will be diagnosed as attention deficit disordered.
Between 1979 and 1983, the New York City school system removed the sugar, additives, and preservatives from its school lunch program. This change alone produced a 15 percent increase in performance on standardized tests. School performance in the New York City School System moved from below national average to above national average. This study was well-controlled, and involved 800,000 children. Other reasons for the outcome were carefully ruled out.
Hypoglycemia is related to hostile, aggressive behavior. This type of response is seen in habitually violent and impulsive criminals. An interesting study in 1984 suggested that reactive hypoglycemia was connected with fire-setting behavior. The study also revealed that the hypoglycemiac arsonists fit the criteria for intermittent explosive disorder, antisocial personality, and borderline personality disorder.
Sugar, white flour, alcohol, caffeine, and tobacco can contribute to low blood sugar. Medications can also induce hypoglycemia including insulin; Bactrim (an antibiotic); beta-blockers such as Propranolol; Haldol; MAO inhibitors; Quinidine; Quinine; and Sulfonylureas, a drug that stimulates beta cells to produce more insulin.
"When nothing else subsists from the past, after the people are dead, after the things are broken and scattered, the smell and taste of things remain poised a long time, like souls bearing resiliently, on tiny and almost impalpable drops of their essence, the immense edifice of memory."
Marcel Proust The Remembrance of Things Past
Mental disorders with olfactory deficits
|Lewy body dementia|
Smell is often our first response to the outside world. It can alert us to dangers, such as smoke or spoiled food. It whets our appetite. It helps us fall in love.
The clinical term for smell is olfaction. Olfaction is related to social affiliation in mammals. The sense of smell is also linked to the sections of the brain that process emotion and learning. The olfactory bulb in the brain is the central area of olfaction. Along with the amygdala and hippocampus, it makes up the limbic system, which mediates our behaviors, mood, and memory.
Olfactory development coincides with development of the forebrain. This is of interest because certain brain disorders include problems with olfaction. For example, small nasal volume and smell identification deficits are found in schizophrenia.
Olfaction consists of several facets, including, detection, identification, and hedonic responses. (Basically, this means that you smell it, you recognize it, and you like it or you don’t like it.)
Almost all of us lose some olfactory senses as we age – the greatest decline occurring between 60 and 100. Olfactory abnormalities have long been documented in psychiatric disorders. Researchers believe that this is, in part, because olfaction is part of our cognitive and emotional circuitry.
Moreover, different types of olfactory deficits are found in different pathologies. For example, people with schizophrenic disorders often have normal odor sensitivity, but exhibit significant deficits in odor identification, recognition, and discrimination. Those suffering from depression will often exhibit deficits in the hedonic aspects of olfaction, even if, in some cases, alterations in sensitivity or identification are also found. In other words, they lose the pleasure of olfaction. Olfactory hallucinations in depression are often those of foul odors. Interestingly, two-thirds of these people believe the odor to emit from their own bodies. A 2008 study by J.F. Dileo showed that in soldiers in PTSD olfactory identification deficits as a predictor of aggression and impulsivity.
Currently, there is no method or single instrument that is universally recognized as being the best tool to detect malingering in PTSD claimants, Guriel J, Fremouw W. Assessing malingered posttraumatic stress disorder: a critical review.
Changes in odor perception in dementia and in some neurodegenerative disease seem to encompass all aspects of the sensorial experience (detection threshold, identification, and recognition). About 90 percent of people with Parkinson's disease have olfactory deficits, and there is evidence for dopaminergic dysfunction underlying these deficits. This is interesting in that children with ADHD tend to have lower levels of dopamine and also have olfactory deficits. Ritalin, a dopamine agonist, not only helps some people with ADHD, but also improves their olfactory senses.
There are several odor assessment tests on the market. The most well-known test is the University of Pennsylvania Smell Identification Test. This is a scratch and sniff test which differentiates types of odor deficits.
“The detection of liver disease often requires a high index of suspicion.”
Catherine C. Crone, MD
Physical symptoms of liver disease
Mental symptoms of liver disease
|Changes in logical thinking|
Liver disease is a common cause of illness and mortality. It can be caused by infections, malignancies, genetic disorders, or toxins. The clinical presentations are highly variable and are often manifested by psychiatric symptoms.
The liver is responsible for many physiological processes, including the synthesis of proteins, metabolizing nutrients, toxins, and drugs. For these reasons, any disease causing liver impairment will have repercussions throughout the body, including impairment of brain function.
Common liver disorders include hepatitis C, alcoholic cirrhosis, Wilson’s disease, porphyria, and liver encephalopathy.
Hepatitis C virus is currently the most common cause of liver disease in the United States and is the most common indication for liver transplants. It’s currently estimated that 170 million people worldwide and four million in the United States are infected.
The most common cause of transmission of Hepatitis C in the United States is intravenous drug use. It can also be transmitted by tattooing.
Various studies have found from 10 to 20 percent of adults with severe mental illnesses are infected with Hepatitis C. It’s estimated that one-third of Americans who are incarcerated are have a hepatitis C infection.
Hepatic encephalopathy is a neuropsychiatric syndrome which often develops in acute or chronic liver disease.
It impairs brain function due to toxins that are normally removed by the liver. Hepatic encephalopathy often presents with disturbances in consciousness, mood, behavior, and cognition. The symptom severity of the disorder varies from minor cognitive impairments to significant confusion, agitation, and disorientation.
After many years of referring milder liver problems as latent, subclinical, or Stage 0 hepatic encephalopathy, the medical community has agreed to use the term minimal hepatic encephalopathy.
Minimal hepatic encephalopathy is found in cirrhotic patients with normal clinical and neurological exams, but they will show impairments on neuropsychological testing.
Cognitive disturbances are subtle, but typically involve psychomotor speed and visual attention and perception. These problems will manifest themselves as personality changes, impairments in work performance, reduced quality of life, sleep problems, and problems with driving.
One of the earliest manifestations is a sleep cycle change – the person will begin to sleep during the day and stay awake at night.
Many studies suggest that minimal hepatic encephalopathy causes poor driving performance.
People with the disorder have a greater self-reported frequency of motor vehicle accidents and traffic violations; therefore, a crucial aspect of the diagnosis is driving history. Unfortunately, asking a person about their driving record is seldom done in a mental health intake.
Several medications are known to cause this disorder, especially benzodiazepines (such as Ativan and Valium), narcotics, and diuretics, and alcohol. Psychometric tests batteries are often used to help detect this disorder. The PSE test (portosystemic encephalopathy test) consists of a combination of established tests, including Trailmaking A and B, and Digit Symbol. Lactulose and probiotics are often effective therapies for this disorder.
Lung diseases such as chronic obstructive pulmonary disease (COPD) asthma, restrictive lung disease, and cystic fibrosis, can causes cognitive impairment, depression, and anxiety. It seems logical that difficulty breathing would cause anxiety; however, research shows that the level of anxiety in lung disease is not correlated with the disease severity.
Over time, hypoxia from lung disease can lead to frontal lobe deficits. Be aware that people with pulmonary disease and breathing problems are often using medications which cause mental symptoms, including corticosteroids, theophylline, β2-Receptor Agonists (Alupen, Advair). Anxiety and sleep problems are known problems. Anticholinergics (Atrovent, Spiriva) may cause fatigue, headache, dizziness, depression, insomnia, and abnormal dreams.
The interaction of heart and mind is an endless loop. Stressful experiences and emotional events affect the heart directly through the autonomic nervous system and indirectly through endocrine pathways. Conversely, abnormalities in the activity of the heart can cause conscious awareness and can caused emotional changes.
There is a significant relationship between diseases of the psyche and cardiovascular system, the association being particularly strong in those with depression, phobias, and anxiety. Many years after cardiac arrest, some people will exhibit mild cerebral impairment. This may present as personality changes, dysinhibition, apathy, or disturbances of judgment.
Patients with chronic non-rheumatic atrial fibrillation showed significantly poorer performances in tasks exploring attention and verbal memory functions, while the paroxysmal group was significantly impaired in a long-term memory task.
Because a majority of heart patients exhibit cognitive deficits and mood problems, many clinicians today suggest that all cardiac patents be screened for mental problems. Many people suffer from post-traumatic stress disorder following myocardial infarction.
There are few experiences that give us the magical feeling of human touch – an essential ingredient in love, pair bonding, and healing. A hug, an embrace, or a kiss, are tactile events that have profound emotional events. In fact, we use the word feeling not only for tactile sensation, but for emotions themselves. Tactile stimulation helps the immune system, lowers blood pressure, and improves mood.
Human skin and the central nervous system are both created from the same tissue – the ectoderm. We express our awareness of this connection with phrases such as, “That really touched me,” ”It makes my skin crawl,” “That gave me goose-bumps,” and “He’s so thin-skinned.”
This interplay of skin and brain has spawned myriad clinical studies. It is clear that skin problems coexist – and contribute to – mental problems. One common finding in the literature is the connection of skin diseases with a high prevalence of depression. Patients seen in general medical practice for other aliments have a prevalence of depression of about 22 percent, but among people with skin disorders the incidence is about 30 percent. The suicide rate in people with skin disorders is also significantly high.
Skin disorders have also been linked to alexithymia. Other psychiatric syndromes frequently found in skin disorders include obsessive-compulsive disorder, social phobia, posttraumatic stress disorder, body image pathologies, delusional disorder, sleep disorders, and personality disorders.
Although it may seem logical that skin diseases could impair a person’s self-image which could result in considerable psychological suffering, the percentage of mood disorders with skin problems is found to be equal to or higher than people suffering from more incapacitating, more disfiguring, more serious, and more painful medical conditions.
Researchers conjecture that both mood disorders and skin disorders are immune mediated, inflammatory states, both with chronic progress and similar comorbidity.
A genetically triggered skin disease known as keratosis follicularis or Darier disease is linked to bipolar disorder and is also associated with mental retardation, schizophrenia, mood disorders, and suicide. It commonly occurs from age six to twenty years of age, but has been seen as early as age four and as late as seventy. This disease is seen more often among men and where the disease course is more severe.
It often presents with bumps on the skin and longitudinal stripes on the fingernails.
A confounding variable in suicide in skin problems is that suicidal thoughts can also be triggered by medications such as interferons, which are used to treat skin disease. Be aware that lithium, a frontline treatment for bipolar disorder is known to cause a variety of skin problems, including psoriasis.
Changes in hair are often a warning signs of physical and mental health. Hair cells are some of the most rapid growing cells the body and, therefore, when the body becomes ill, it is not uncommon that hair cells shut down resulting in changes in hair structure or hair loss. These changes can be triggered by hormonal changes, malnutrition, medication, and many medical disorders, especially thyroid disease.
People with red hair are more likely to have a receptor gene that can affect sensitivity to anaesthetics and response to pain.
Hair loss can also be a sign of a lack of certain nutrients, such as zinc and biotin. Some people develop hair loss after bariatric surgery that makes changes in their digestive system and decreases their zinc absorption.
People often experience hair loss because of hyperthyroidism or hypothyroidism. These disorders are frequently misdiagnosed as affective disorders, mainly depression and anxiety.
People suffering from heartburn and acid reflux frequently take antacids (including Nexium and Prilosec) which interfere with B vitamin absorption, including B12 and biotin. Low levels of B12 and biotin often cause hair loss, but can also lead to skin rashes, heart problems, anxiety, depression, lethargy, and at times, hallucinations.
"We've all been told you ought to sleep eight hours, but there is never any evidence"
Mental symptoms of poor sleep
|Increased body mass index|
|Using alcohol to sleep|
|Using drugs to sleep|
Sleep problems and biological rhythms disorders have long been tied to mental health problems. Disruption in normal sleep is associated with increased irritability and aggression. For this reason, an assessment of the quality and quantity of sleep is essential for an accurate mental diagnosis. It would also be prudent to get a sleep history of the family.
The amount of sleep a person needs differs significantly from person to person. The belief that everyone should sleep eight hours can cause people to assume they have insomnia. This often gets them a prescription for sleeping pills, which they don’t need.
The amount of sleep an individual needs is, in part, genetic. Recently it was discovered that about three percent of humans have a gene called DEC2. People who possess this gene have a normal sleep cycle of 6.0 hours per night.
There have been significant changes in self-reported sleep duration over the past half century. A sleep survey in 1960, which polled over a million people, found that the modal sleep duration was 8.0 to 8.9 hours a night. But surveys done in 2000, 2001, and 2002 found the average duration of sleep for Americans had fallen to 6.9-7.0 hours. In 2009, it was observed that many people slept only 5.0-6.0 hours per night on a regular basis. Chronic sleep deprivation is linked to injuries and motor vehicle accidents, problems with short-term memory, impairment in attention, depressed mood, and inability to control appetite.
Problems of shiftworkers
|Higher sick leave|
Statistically, people who sleep between six to seven hours a night live the longest. Conversely, shift workers, who seldom get adequate sleep, have a perpetual sleep debt which puts them at high risk for a number of pathologies, including cardiovascular disease, digestive disorders, and psychiatric problems. Shift workers (people who work at night, or change shifts frequently) do not adjust to their sleep patterns, and the risk of their problems increases over time. They also have a significantly higher rate of relationship and family problems.
Lithium seems to improve the symptoms of bipolar disorder, in part, by normalizing the circadian clock. The mineral reduces the activity of Rev-erb-alpha, a receptor in the brain that turns off circadian clock genes. (It is also known that in regions of the world where there are low levels of lithium in the water supply, there are higher incidents of incidence suicide, homicide, and violent behaviors.)
Physical symptoms of sleep apnea
|Excessive daytime sleepiness|
|Morning or evening headaches|
|Heartburn at night|
|Swelling of legs|
|Choking or gasping during sleep|
Breastfeeding alters a baby’s mouth, shaping it properly to allow adequate airflow. Breastfeeding requires less forceful sucking than bottle-feeding and a more proper tongue placement (forward position in the mouth). This contributes to a lower roof arch and better breathing. The newborn’s palate, being soft and malleable, is sculpted by sucking and swallowing. This primary repetitive motion of infancy shapes breathing patterns through adulthood.
Bottlefeeding, on the other hand, often causes incorrect positioning of the tongue. Because bottle nipples are much firmer than a human breast, the tongue position leads to a different tongue thrust and an incorrect formation of the palate. In adulthood, this increases the risk of sleep-disordered breathing problems. Brian Palmer, a dentist and researcher in Leawood, Kansas, believes that bottle-fed infants display a significantly different sucking pattern and tongue position than breastfed babies. Bottle-fed babies do not have same experience, and may have air intake problems. They also have a higher incidence of obstructive sleep apnea later in life.
Take a deep breath and hold it as long as you possibly can. In less than a minute, you will have an overwhelming panicky feeling that will cause you to take a deep breath. You have just experienced apnea.
Any abnormal breathing while sleeping is called sleep apnea. About two-and-a-half-million people in the United States suffer from sleep apnea, but the majority of them are unaware of the problem.
There are three basic types of apnea, obstructive, central, and complex. Obstructive sleep apnea is the physical collapse of the airway. This is often caused by excess weight. Although obesity is a common cause of obstructive apnea, other medical conditions include a reduction in muscle tone of the soft palate, a short thick neck, the uvula (the small, conical, fleshy tissue hanging from the center of the soft palate), and the pharynx. The upper airway can also be narrowed by enlarged tonsils, adenoids, deviated nasal septums, nasal polyps, or congenital airway abnormalities.
Obstructive sleep apnea and hypothyroidism have many signs and symptoms in common. A sleep study at the University of Calgary showed that four percent of people with obstructive apnea had undiagnosed hypothyroidism. This type of hypothyroid sleep-disordered breathing can often be treated with thyroxine.
Central apnea is the phenomenon of the cessation of breathing. People with central apnea often have damage or abnormalities in brain regions that regulate breathing and speech. As a result, almost 40 percent of people with central apnea also stuttered as children. Children with central apnea are often misdiagnosed with attention deficit disorder, because their poor sleep quality makes them drowsy during the day. Since stuttering is a treatable problem, people may not be aware that they still have apnea.
Complex sleep apnea is the presence of central apnea plus obstructive apnea. About 15 percent of all sleep apnea patients have complex apnea.
There is a strong association between episodic hypoxia and sleep fragmentation with memory deficits, attention, global intelligence, hyperactive behaviors, and mood disturbances.
Children with apnea are often misdiagnosed with attention deficit hyperactivity disorder (ADHD). Because they sleep poorly, they cannot focus in the classroom. In a 2003 study by sleep researcher Louise O’Brien, 44 children with symptoms of ADHD spent a night in a sleep lab. Obstructive sleep apnea was found in five percent of those with significant ADHD symptoms, and twenty-six percent of those with mild symptoms, but only five percent of had no symptoms. A high prevalence of snoring was identified among a group of children designated as showing mild symptoms of ADHD. Rapid eye movement disturbances are more likely to occur in children with significant symptoms, and they seem to impose significant effects on daytime behavior.
Another study focused on snoring, sleep disordered breathing, and problem behaviors in five-year-old children. The parents reported that children who snored and those that exhibited daytime sleepiness also presented with hyperactivity, inattention, and aggressiveness. The study revealed that sleep-disordered breathing symptoms are common in five-year-old children resulting in behaviors that suggested attention-deficit/hyperactivity disorder.
These children may be given a stimulant such as Ritalin. Although the stimulant may make a child more alert, it will not cure the problem; in fact, the drugs may actually interfere with sleep. Sometimes removing the tonsils helps, by virtue of improving airflow through the throat.
While ADHD is more likely to be diagnosed in children with apnea, adults with apnea are more often misdiagnosed with depression. One in five people with depression is likely to have apnea. Adults with sleep apnea are three times more likely to also have diabetes.
Obesity hypoventilation syndrome is under-recognized, misdiagnosed, and under-treated. Because obesity has become a national epidemic, it is important that all health care professionals learn to recognize these disorders.
Some symptoms of apnea – such as awakening with feeling of choking, abnormal motor activity during sleep, and the excessive daytime sleepiness – are commonly found in obstructive apnea, but are also found in nocturnal frontal lobe epilepsy. For this reason, a sleep study should be done to identify the origin of these symptoms.
In addition, both men and women with apnea also have a high incidence of sexual dysfunction. Men who suffer from obstructive sleep apnea produce lower levels of testosterone.
Many of these symptoms of apnea will improve reduced through continuous positive airway pressure (CPAP) treatment. Other treatments include surgery to remove soft tissue in the mouth and increase airflow.
Robert Kendell, M.D.; Assen Jablensky, M.D. Distinguishing Between the Validity and Utility of Psychiatric Diagnoses. The American Journal of Psychiatry. Volume 160 Issue 1, January 2003, pp. 4-12.
Castro J, Billick S. Psychiatric presentations/manifestations of medical illnesses. Psychiatr Q. 2013 Sep;84(3):351-62.
Lampe L, Shadbolt N, Starcevic V, Boyce P, et al. Diagnostic processes in mental health: GPs and psychiatrists reading from the same book but on a different page. Australas Psychiatry. 2012 Oct;20(5):374-8.
Berner, ES. Graber, ML. Overconfidence as a Cause of Diagnostic Error in Medicine. Am Journ Med 2008. 121(5A):S2–S23.
Hibbeln JR, Gow RV. The potential for military diets to reduce depression, suicide, and impulsive aggression: a review of current evidence for omega-3 and omega-6 fatty acids. Mil Med. 2014 Nov;179(11 Suppl):117-28.
Koranyi EK. Morbidity and rate of undiagnosed physical illnesses in a psychiatric clinic population. Arch Gen Psychiatry. 1979 Apr; 36(4):414-9.
Hall RC, Popkin MK, Devaul RA, Faillace LA, Stickney SK. Physical illness presenting as psychiatric disease. Arch Gen Psychiatry. 1978 Nov; 35(11):1315-20.
Hibbeln JR, Nieminen LR, Lands WE. Increasing homicide rates and linoleic acid consumption among five Western countries, 1961-2000. Lipids. 2004 Dec; 39(12):1207-13.
Koran LM, Sox HC Jr, Marton KI, Moltzen S, Sox CH, Kraemer HC, Imai K, Kelsey TG, Rose TG Jr, Levin LC, et al. Medical evaluation of psychiatric patients. I. Results in a state mental health system. Arch Gen Psychiatry. 1989 Aug; 46(8):733-40.
Paley, J. Satanist abuse and alien abduction: A comparative analysis theorizing temporal lobe activity as a possible connection between anomalous memories. British Journal of Social Work Volume 27, Number 1 Pp. 43-70.
Spanos NP, Burgess CA, Burgess MF. Past-life identities, UFO abductions, and satanic ritual abuse: the social construction of memories. Int J Clin Exp Hypn. 1994 Oct;42(4):433-46.
Wang C, Alexander G, Berman N, Salehian B, Davidson T, McDonald V, Steiner B, Hull L, Callegari C, Swerdloff RS. Testosterone replacement therapy improves mood in hypogonadal men – a clinical research center study. J Clin Endocrinol Metab. 1996 Oct; 81(10):3578-83.
Druss BG, Bornemann TH. Improving health and health care for persons with serious mental illness: the window for US federal policy change. JAMA. 2010 May 19;303(19):1972-3.
Viron MJ, Stern TA. The impact of serious mental illness on health and healthcare. Psychosomatics. 2010 Nov-Dec;51(6):458-65.
Parks, J., et al. Morbidity and mortality in people with serious mental illness. National Association of State Mental Health Program Directors (NASMHPD) 2006 Oct.
Kessler RC, Sampson NA, Berglund P, Gruber MJ., Anxious and non-anxious major depressive disorder in the World Health Organization World Mental Health Surveys. Epidemiol Psychiatry Sci. 2015 Feb 27:1-17.
Aina Y, Susman JL. Understanding comorbidity with depression and anxiety disorders. J Am Osteopath Assoc. 2006 May; 106(5 Suppl 2):S9-14.
Jerome Goopman MD How Doctors Think March 12, 2008.
Fred Ovsiew, MD Introduction: Neuropsychiatry Is Thriving. Psychiatric Times February 27, 2015.
Carson AJ, Stone J, Hansen CH, Duncan R, et al. Somatic symptom count scores do not identify patients with symptoms unexplained by disease: a prospective cohort study of neurology outpatients. J Neurol Neurosurg Psychiatry. 2015 Mar;86(3):295-301.
Carson AJ, Ringbauer B, Stone J, McKenzie L, Warlow C, Sharpe M. Do medically unexplained symptoms matter? A prospective cohort study of 300 new referrals to neurology outpatient clinics. J Neurol Neurosurg Psychiatry. 2000 Feb; 68(2):207-10.
Frances A, Chapman S. DSM-5 somatic symptom disorder mislabels medical illness as mental disorder. Aust N Z J Psychiatry. 2013 May;47(5):483-4.
Katon WJ, Walker EA. Medically unexplained symptoms in primary care. J Clin Psychiatry. 1998; 59 Suppl 20:15-21.
Naga AA, Devinsky O, Barr WB. Somatoform disorders after temporal lobectomy. Cogn Behav Neurol. 2004 Jun; 17(2):57-61.
Daum C, Gheorghita F, Spatola M, Stojanova V, et al. Interobserver agreement and validity of bedside 'positive signs' for functional weakness, sensory and gait disorders in conversion disorder: a pilot study. J Neurol Neurosurg Psychiatry. 2015 Apr;86(4):425-30.
Baslet G, Dworetzky B, Perez DL, Oser M. Treatment of psychogenic nonepileptic seizures: updated review and findings from a mindfulness-based intervention case series. Clin EEG Neurosci. 2015 Jan;46(1):54-64.
John Jesitus NEUROLOGY: Teamwork and tact for conversion disorders. Contemporary Pediatrics November 01, 2014.
Voon V, Ekanayake V, Wiggs E, Kranick S, Ameli R, Harrison NA, Hallett M. Response inhibition in motor conversion disorder. Mov Disord. 2013 Apr 2.
Daum C, Aybek S. Validity of the "Drift without pronation" sign in conversion disorder.
BMC Neurol. 2013 Apr 1;13:31.
Heijmans M, Olde Hartman TC, van Weel-Baumgarten E, Dowrick C, Lucassen PL, van Weel C. Experts' opinions on the management of medically unexplained symptoms in primary care. A qualitative analysis of narrative reviews and scientific editorials. Fam Pract. 2011 Aug;28(4): 444-55.
Derakhshan I. The preservation of consciousness, automatism, and movement control. J Neuropsychiatry Clin Neurosci. 2003 Fall; 15(4):456-7.
Devinsky O, Mesad S, Alper K. Nondominant hemisphere lesions and conversion nonepileptic seizures. J Neuropsychiatry Clin Neurosci. 2001 Summer; 13(3):367-73.
Ramasubbu R. Conversion sensory symptoms associated with parietal lobe infarct: case report, diagnostic issues and brain mechanisms. J Psychiatry Neurosci. 2002 Mar; 27(2):118-22.
Vardi J, Finkelstein Y, Zlotogorski Z. Parietal circuits and conversion seizures. J Neuropsychiatry Clin Neurosci. 2002 Fall; 14(4):468.
Showalter, Elaine Hystories: Hysterical Epidemics and Modern Media Columbia University Press, 1998.
van der Feltz-Cornelis CM, van Houdenhove B. [DSM-5: from 'somatoform disorders' to 'somatic symptom and related disorders']. Tijdschr Psychiatr. 2014;56(3):182-6.
Fishbain DA, Lewis JE, Gao J, Cole B, Steele Rosomoff R. Is chronic pain associated with somatization/ hypochondriasis? An evidence-based structured review. Pain Pract. 2009 Nov-Dec;9(6):449-67.
Katz-Sidlow RJ. In the Darwin family tradition: another look at Charles Darwin's ill health. J R Soc Med. 1998 Sep;91(9):484-8.
Massey EW, Riley TL. Pseudoseizures: recognition and treatment. Psychosomatics. 1980 Dec; 21(12):987-91, 996-7.
Wick JY, Zanni GR. Hypochondria: the worried well. Consult Pharm. 2008 Mar;23(3):192-4, 196-8, 207-8.
Dauncey MJ. Recent advances in nutrition, genes and brain health. Proc Nutr Soc. 2012 Nov;71(4):581-91.
Dauncey MJ. Genomic and epigenomic insights into nutrition and brain disorders. Nutrients. 2013 Mar 15;5(3):887-914.Mueller EM, Stemmler G, Hennig J, Wacker J. 5-HTTLPR and anxiety modulate brain-heart covariation. Psychophysiology. 2013 May;50(5):441-53.
[No author cited] Serotonin transporter gene shown to influence college drinking habits NIH News. August 18, 2003. http://www.nih.gov/news/ pr/aug2003/ niaaa-18.htm [Accessed September 20, 2006]
[No author cited] Depression gene may weaken mood-regulating circuit. [Accessed October 3, 2006]
Chen CK, Lin SK, Sham PC, Ball D, Loh el-W, Murray RM. Morbid risk for psychiatric disorder among the relatives of methamphetamine users with and without psychosis. Am J Med Genet B Neuropsychiatr Genet. 2005 Jul 5; 136(1):87-91.
Coghlan, A. Human-chimp DNA difference trebled. NewScientist.com September 23, 2002. [Accessed Sunday, August 02, 2009]
Gill, ML, Genes and mental health. Department of Psychiatry, Trinity College Dublin, Draft. 4 October 2004.
Haberstick BC, Lessem JM, Hopfer CJ, Smolen A, Ehringer MA, Timberlake D, Hewitt JK. Monoamine oxidase A (MAOA) and antisocial behaviors in the presence of childhood and adolescent maltreatment. Am J Med Genet B Neuropsychiatr Genet. 2005 May 5; 135(1):59-64.
Kuratomi Go, Iwamoto Kazuya, Bundo Miki, Kusumi Ichiro, Kato Nobumasa, Iwata Nakao, Ozaki Norio, Kato Tadafumi. Aberrant DNA methylation associated with bipolar disorder identified from discordant monozygotic twins. Molecular Psychiatry. 2008. 13, 429-441.
Kuzelova H, Ptacek R, Macek M. The serotonin transporter gene (5-HTT) variant and psychiatric disorders: review of current literature. Neuro Endocrinol Lett. 2010 Feb 16; 31(1):5.
McManamy, J. The other brain cell. McMan's depression and bipolar web. [Accessed August 2, 2009]
Miller L, Warner V, Wickramaratne P, Weissman M. Religiosity and depression: ten-year follow-up of depressed mothers and offspring. J Am Acad Child Adolesc Psychiatry. 1997 Oct; 36(10):1416-25.
Stokstad E. Psychology. Violent effects of abuse tied to gene. Science. 2002 Aug 2; 297(5582): 752. [No abstract available]
Storfer, Miles G. Intelligence and giftedness: The contribution of heredity and early environment. Jossey-Bass, 1990.
Verdeli H, Ferro T, Wickramaratne P, Greenwald S, Blanco C, Weissman MM. Treatment of depressed mothers of depressed children: pilot study of feasibility. Depress Anxiety. 2004; 19(1):51-8.
Schmitz A, Grillon C, Avenevoli S, Cui L, Merikangas KR. Developmental investigation of fear-potentiated startle across puberty. Biol Psychol. 2014 Mar;97:15-21.
Weissman MM, Wickramaratne P, Nomura Y, Warner V, Verdeli H, Pilowsky DJ, Grillon C, Bruder G. Families at high and low risk for depression: a 3-generation study. Arch Gen Psychiatry. 2005 Jan; 62(1):29-36.
Zubenko GS, Zubenko WN, Spiker DG, Giles DE, Kaplan BB. Malignancy of recurrent, early-onset major depression: a family study. Am J Med Genet. 2001 Dec 8; 105(8):690-9.
Patrick RP, Ames BN. Vitamin D and the omega-3 fatty acids control serotonin synthesis and action, part 2: relevance for ADHD, bipolar, schizophrenia, and impulsive behavior. FASEB J. 2015 Feb 24.Niculescu AB, Levey D, Le-Niculescu H, Niculescu E, Kurian SM, Salomon D(4). Psychiatric blood biomarkers: avoiding jumping to premature negative or positive conclusions. Mol Psychiatry. 2015 Mar;20(3):286-8.
Le-Niculescu H, Kurian SM, Yehyawi N, Dike C, Patel SD, Edenberg HJ, Tsuang MT, Salomon DR, Nurnberger JI Jr, Niculescu AB. Identifying blood biomarkers for mood disorders using convergent functional genomics. Mol Psychiatry. 2009 Feb; 14(2):156-74.
Webb RT, Abel KM, Pickles AR, Appleby L, King-Hele SA, Mortensen PB. Mortality risk among offspring of psychiatric inpatients: a population-based follow-up to early adulthood. Am J Psychiatry. 2006 Dec; 163(12):2170-7.
Webb RT, Pickles AR, King-Hele SA, Appleby L, Mortensen PB, Abel KM. Parental mental illness and fatal birth defects in a national birth cohort. Psychol Med. 2007 Dec 13; :1-9.
Covault J, Tennen H, Armeli S, Conner TS, Herman AI, Cillessen AH, Kranzler HR. Interactive effects of the serotonin transporter 5-HTTLPR polymorphism and stressful life events on college student drinking and drug use. Biol Psychiatry. 2007 Mar 1; 61(5):609-16. Epub 2006 Aug 22.
Herman AI, Philbeck JW, Vasilopoulos NL, Depetrillo PB. Serotonin transporter promoter polymorphism and differences in alcohol consumption behaviour in a college student population. Alcohol Alcohol. 2003 Sep-Oct; 38(5):446-9.
Paterson DS, Trachtenberg FL, Thompson EG, Belliveau RA, Beggs AH, Darnall R, Chadwick AE, Krous HF, Kinney HC. Multiple serotonergic brainstem abnormalities in sudden infant death syndrome. JAMA. 2006 Nov 1; 296(17):2124-32.
Maier R, Moser G, Chen GB, Ripke S; Weissman MM Joint analysis of psychiatric disorders increases accuracy of risk prediction for schizophrenia, bipolar disorder, and major depressive disorder. Am J Hum Genet. 2015 Feb 5;96(2):283-94.
Olesen PJ, Gustafson DR, Simoni M, Pantoni L, Ostling S, Guo X, Skoog I. Temporal lobe atrophy and white matter lesions are related to major depression over 5 years in the elderly. Neuropsycho- pharmacology. 2010 Dec;35(13):2638-45.
Deuschle M, Schweiger U. [Depression and diabetes mellitus type 2.] Nervenarzt. 2012 Oct 17. [Article in German]
Weissman MM, Wickramaratne P, Nomura Y, Warner V, Verdeli H, Pilowsky DJ, Grillon C, Bruder G. Families at high and low risk for depression: a 3-generation study. Arch Gen Psychiatry. 2005 Jan; 62(1):29-36.
Zubenko GS, Zubenko WN, Spiker DG, Giles DE, Kaplan BB. Malignancy of recurrent, early-onset major depression: a family study. Am J Med Genet. 2001 Dec 8; 105(8):690-9.
Fahim S, van Duijn CM, Baker FM, Launer L, Breteler MM, Schudel WJ, Hofman A. A study of familial aggregation of depression, dementia and Parkinson's disease. Eur J Epidemiol. 1998 Apr; 14(3):233-8.
McGuffin P, Katz R, Watkins S, Rutherford J. A hospital-based twin register of the heritability of DSM-IV unipolar depression. Arch Gen Psychiatry. 1996 Feb; 53(2):129-36.
Fahim S, van Duijn CM, Baker FM, Launer L, Breteler MM, Schudel WJ, Hofman A. A study of familial aggregation of depression, dementia and Parkinson's disease. Eur J Epidemiol. 1998 Apr; 14(3):233-8.
Awara MA, Zahid S, Elnenaei MO. Rapid cycling bipolar affective disorder and recurrent strokes secondary to high blood homocysteine. J Ment Health. 2012 May 1.
Kimmel RJ, Kovacs I, Vrabel C, Wood B, Schalling M, Kelsoe JR. Co-segregation of bipolar disorder and autosomal-dominant medullary cystic kidney disease in a large family. Am J Psychiatry. 2005; 162: 1972-1974.
Christodoulou K, Tsingis M, Stavrou C, Eleftheriou A, Papapavlou P, Patsalis PC, Ioannou P, Pierides A, Constantinou Deltas C. Chromosome 1 localization of a gene for autosomal dominant medullary cystic kidney disease. Hum Mol Genet. 1998 May; 7(5):905-11.
Chiaroni P, Hantouche EG, Gouvernet J, Azorin JM, Akiskal HS. [Hyperthymic and depressive impairments study in controls, as a function of their familial loading for mood disorders.] Encephale. 2004 Nov-Dec; 30(6):509-15. [Article in French]
Akiskal HS. The bipolar spectrum: the shaping of a new paradigm. Curr Psychiatry Rep. 2002; 4:1-3.
Henin A, Biederman J, Mick E, Sachs GS, Hirshfeld-Becker DR, Siegel RS, McMurrich S, Grandin L, Nierenberg AA. Psychopathology in the offspring of parents with bipolar disorder: a controlled study. Biol Psychiatry. 2005 Oct 1; 58(7):554-61. Epub 2005 Aug 22.
Richards R, Kinney DK, Lunde I, Benet M, Merzel AP. Creativity in manic-depressives, cyclothymes, their normal relatives, and control subjects. J Abnorm Psychol. 1988; 97:281-288.
Severance EG, Prandovszky E, Castiglione J, Yolken RH. Gastroenterology issues in schizophrenia: why the gut matters. Curr Psychiatry Rep. 2015 May;17(5):574.
Xia Y, Qi F, Zou J,Yang J, Yao Z. Influenza vaccination during early pregnancy contributes to neurogenesis and behavioral function in offspring. Brain Behav Immun. 2014 Jul 8.Bronson SL Bale TL. Prenatal stress-induced increases in placental inflammation and offspring hyperactivity are male-specific and ameliorated by maternal anti inflammatory treatment. Endocrinology. 2014 Jul;155(7):2635-46.
Chen CK, Lin SK, Sham PC, Ball D, Loh el-W, Murray RM. Morbid risk for psychiatric disorder among the relatives of methamphetamine users with and without psychosis. Am J Med Genet B Neuropsychiatr Genet. 2005 Jul 5; 136(1):87-91.
Alanen Yo, Rekola J, Stewen A, Tuovinen M, Takala K, Rutanen E. Mental disorders in the siblings of schizophrenic patients. Acta Psychiatr Scand. 1963; 39: Suppl 169:167.
Le-Niculescu H, et al. Toward understanding the schizophrenia code: an expanded convergent functional genomics approach. Am J Med Genet B Neuropsychiatr Genet. 2007 Mar 5; 144B(2):129-58.
Nurnberger JI Jr, Faraone SV, Tsuang MT, Niculescu AB. Toward understanding the schizophrenia code: an expanded convergent functional genomics approach. Am J Med Genet B Neuropsychiatr Genet. 2007 Mar 5; 144B(2):129-58.
Phillips M, Erickson GA, Sabas M, Smith JP, Greenberg J. Volatile organic compounds in the breath of patients with schizophrenia. J Clin Pathol. 1995 May;48(5):466-9.
Wolfram syndrome Genetics Home Reference. NIH.gov. Reviewed April 2012.
Sen S. Shared genetic risk factors for psychiatric illness. Acta Psychiatr Scand. 2014 Oct;130(4):243.
Swift RG, Sadler DB, Swift M. Psychiatric findings in Wolfram syndrome homozygotes. Lancet. 1990 Sep 15; 336(8716):667-9.
Swift M, Swift RG. Wolframin mutations and hospitalization for psychiatric illness. Mol Psychiatry. 2005 Aug; 10(8):799-803.
Swift RG, Polymeropoulos MH, Torres R, Swift M. Predisposition of Wolfram syndrome heterozygotes to psychiatric illness. Mol Psychiatry. 1998 Jan; 3(1):86-91.
Wolfram D J, Wagener HP. Diabetes mellitus and simple optic atrophy among siblings: report of four cases. Mayo Clin. Proc. 1938; 13: 715-718.
Ward RJ, Dexter DT, Crichton RR. Neurodegenerative diseases and therapeutic strategies using iron chelators. J Trace Elem Med Biol. 2015 Jan 22.
Yeap BB, Divitini ML, Gunton JE, Olynyk JK, Beilby JP, McQuillan B, Hung J, Knuiman MW. Higher ferritin levels, but not serum iron or transferrin saturation, are associated with Type 2 diabetes mellitus in adult men and women free of genetic haemochromatosis. Clin Endocrinol (Oxf). 2015 Apr;82(4):525-32.Serata D, Del Casale A, Rapinesi C, et al. Hemochromatosis-induced bipolar disorder: a case report. Gen Hosp Psychiatry. 2012 Jan-Feb;34(1):101.e1-3.
Rogers JT, Lahiri DK. Metal and inflammatory targets for Alzheimer's disease. Curr Drug Targets. 2004 Aug; 5(6):535-51.
Kley HK, Stremmel W, Kley JB, Schlaghecke R. Testosterone treatment of men with idiopathic hemochromatosis. Clin Investig. 1992 Jul; 70(7):566-72.
Feifel D, Young CW. Iron overload among a psychiatric outpatient population. J Clin Psychiatry. 1997 Feb; 58(2):74-8.
Van Deursen C, Delaere K, Tenkate J. Hemochromatosis and sexual dysfunction. Int J Impot Res. 2003 Dec; 15(6):430-2.
Dalvi A. Wilson's disease: neurological and psychiatric manifestations. Dis Mon. 2014 Sep;60(9):460-4.
Iwański S, Seniów J, Leśniak M, Litwin T, Członkowska A. Diverse attention deficits in patients with neurologically symptomatic and asymptomatic Wilson's disease. Neuropsychology. 2015 Jan;29(1):25-30.
Strand NA, Deurell M, Olsen EM. [Wilson disease often debuts with psychiatric symptoms.]
Ugeskr Laeger. 2014 Sep 15;176(38). [Article in Danish]
Akil M, Brewer GJ. Psychiatric and behavioral abnormalities in Wilson's disease. Adv Neurol. 1995; 65:171-8.
Dening TR, Berrios GE. Wilson's disease: a prospective study of psychopathology in 31 cases. Br J Psychiatry. 1989 Aug; 155:206-13.
Dening TR. The neuropsychiatry of Wilson's disease: a review. Int J Psychiatry Med. 1991; 21(2):135-48.
Portala K, Westermark K, von Knorring L, Ekselius L. Psychopathology in treated Wilson's disease determined by means of CPRS expert and self-ratings. Acta Psychiatr Scand. 2000 Feb;101(2):104-9.
Walshe JM, Yealland M. Wilson's disease: the problem of delayed diagnosis. J Neurol Neurosurg Psychiatry. 1992 Aug; 55(8):692-6.
What is Klinefelter syndrome? Genetics Home Reference. NIH.gov. Reviewed January 2013.
Skakkebaek A, Bojesen A, Kristensen MK, Cohen A, et al. Neuropsychology and brain morphology in Klinefelter syndrome - the impact of genetics. Andrology. 2014 Jul;2(4):632-40.Seminog OO, Seminog AB, Yeates D, Goldacre MJ. Associations between Klinefelter's syndrome and autoimmune diseases: English national record linkage studies. Autoimmunity. 2014 Oct 8:1-4.
Swanson DW, Stipes AH. Psychiatric aspects of Klinefelter's syndrome. Am J Psychiatry. 1969 Dec; 126(6):814-22.
Van Rijn S, Swaab H, Aleman A, Kahn RS. X Chromosomal effects on social cognitive processing and emotion regulation: a study with Klinefelter men (47,XXY). Schizophr Res. 2006 Jun; 84(2-3):194-203.
Kebers F, Janvier S, Colin A, Legros JJ, Ansseau M. [What is the interest of Klinefelter's syndrome for (child) psychiatrists?] Encephale. 2002 May-Jun; 28(3 Pt 1):260-5. [Article in French]
Venerito M, Radünz M, Reschke K, Reinhold D, Frauenschläger K, et al. Autoimmune gastritis in autoimmune thyroid disease. Aliment Pharmacol Ther. 2015 Apr;41(7):686-93.
Guan LJ, Wang X, Meng S, Shi LF, Jiang WJ et al. Xu J(3), Zhang JA(4). Increased IL-21/IL-21R expression and its proinflammatory effects in autoimmune thyroid disease. Cytokine. 2015 Apr;72(2):160-5.Capetillo-Ventura N, Baeza I. Psychiatric Symptoms due to Thyroid Disease in a Female Adolescent. Case Rep Endocrinol. 2014;2014:972348.
Lawrence C. Wood, MD, FACP. Learning Disabilities in Patients with Autoimmune Thyroid Disease and Their Families. Thyrobulletin, Vol. 7, No. 1. 2000.
de Sousa RT, Uno M, Zanetti MV, Shinjo SM, Busatto GF, Gattaz WF, Marie SK, Machado-Vieira R. Leukocyte mitochondrial DNA copy number in bipolar disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2014 Jan 3;48:32-5.
Kato T. Molecular neurobiology of bipolar disorder: a disease of 'mood-stabilizing neurons'? Trends Neurosci. 2008 Oct; 31(10):495-503.
Washizuka Shinsuke, Iwamoto Kazuya, Kakiuchi Chihiro, Bundo Miki, Kato T. Expression of mitochondrial complex I subunit gene NDUFV2 in the lymphoblastoid cells derived from patients with bipolar disorder and schizophrenia. Neurosci Res. 2009;, 63:199-204.
Kato T. The other forgotten genome: mitochondrial DNA and mental disorders. Molecular Psychiatry. 2001; 6: 625-633.
Kato T. Molecular neurobiology of bipolar disorder: a disease of 'mood-stabilizing neurons'? Trends Neurosci. 2008 Oct; 31(10):495-503.
El-Sayed AM, Koenen KC, Galea S. Putting the 'epi' into epigenetics research in psychiatry. J Epidemiol Community Health. 2013 Apr 18.
Brogan K. Perinatal depression and anxiety: beyond psychopharmacology. Psychiatr Clin North Am. 2013 Mar;36(1):183-8.Costanza A, D'Orta I, Perroud N, Burkhardt S, Malafosse A, Mangin P, La Harpe R. Neurobiology of suicide: do biomarkers exist? Int J Legal Med. 2013 Feb 22.
Cropley JE, Suter CM, Beckman KB, Martin DIK. Germ-line epigenetic modification of the murine avy allele by nutritional supplementation. Proc Natl Acad Sci U S A. 2006;; 103:17308 –17312.
Csoka AB, Szyf M. Epigenetic side-effects of common pharmaceuticals: A potential new field in medicine and pharmacology. Med Hypotheses. 2009 Jun 4.
Isles AR, Wilkinson LS. Epigenetics: what is it, and why is it important to mental disease? Br Med Bull. 2008; 85:35-45.
Nestler EJ. Epigenetic mechanisms in psychiatry. Biol Psychiatry. 2009 Feb 1; 65(3):189-90.
Neuman RJ, Lobos E, Reich W, Henderson CA, Sun LW, Todd RD. Prenatal smoking exposure and dopaminergic genotypes interact to cause a severe ADHD subtype. Biol Psychiatry. 2007 Jun 15; 61(12):1320-8.
Ridley, Matt. Which is stronger – nature or nurture? The latest science says genes and your experience interact for your whole life. Time Magazine. Monday, Jun 2, 2003.
Szyf M. The dynamic epigenome and its implications in toxicology. Toxicol Sci. 2007 Nov;; 100(1):7-23.
Yu-Fen Li, Bryan Langholz, Muhammad T. Salam, and Frank D. Gilliland, Maternal and grandmaternal smoking patterns are associated with early childhood asthma. Chest. 2005 April; 127(4):1232-1240.
Yang FY, Lu WW, Lin WT, Chang CW, Huang SL. Enhancement of Neurotrophic Factors in Astrocyte for Neuroprotective Effects in Brain Disorders Using Low-intensity Pulsed Ultrasound Stimulation. Brain Stimul. 2014 Dec 4.
Chen PS, et al. Valproate protects dopaminergic neurons in midbrain neuron/glia cultures by stimulating the release of neurotrophic factors from astrocytes. Mol Psychiatry. 2006 Dec; 11(12):1116-25.
Friedberg, JM. Letter to the Editor: Astrocytic Activation as Evidence for Brain Damage Am J Psychiatry. 2005 Jan. 162:195-196.
Moises HW, Zoega T, Gottesman II. The glial growth factors deficiency and synaptic destabilization hypothesis of schizophrenia. BMC Psychiatry. 2002; 2:8
McManamy, J. The other brain cell. McMan's depression and bipolar web. [Accessed September 9, 2010].
Colman I, Jones PB, Kuh D, Weeks M, Naicker K, Richards M(3), Croudace TJ(4). Early development, stress and depression across the life course: pathways to depression in a national British birth cohort. Psychol Med. 2014 Oct;44(13):2845-54.Brown GR, Spencer KA. Steroid hormones, stress and the adolescent brain: A comparative perspective. Neuroscience. 2012 Dec 20.
Akhondzadeh S, Tabatabaee M, Amini H, Ahmadi Abhari SA, Abbasi SH, Behnam B. Celecoxib as adjunctive therapy in schizophrenia: a double-blind, randomized and placebo-controlled trial. Schizophr Res. 2007 Feb; 90(1-3):179-85.
Bresee CJ, Delrahim K, Maddux RE, Dolnak D, Ahmadpour O, Rapaport MH. The effects of celecoxib augmentation on cytokine levels in schizophrenia. Int J Neuropsychopharmacol. 2006 Jun; 9(3):343-8. Epub 2005 Jul 22.
Caspi A, McClay J, Moffitt TE, Mill J, Martin J, Craig IW, Taylor A, Poulton R. Role of genotype in the cycle of violence in maltreated children. Science. 2002 Aug 2; 297(5582):851-4.
Costello EJ, Worthman C, Erkanli A, Angold A. Prediction from low-birth weight to female adolescent depression. Arch Gen Psychiatry. 2007 Mar; 64.
Cynader MS, Frost BJ. Mechanisms of brain development: Neuronal sculpting by the physical and social environment. In D. P. Keating & C. Hertzman (Eds.) Developmental health and the wealth of nations: social, biological, and educational dynamics. New York: Guilford Press, 1999.
Erick de Messias. Schizophrenia and season of birth in a tropical region: relationship to rainfall. Schizophrenia Research, vol 48, p 227, 2001.
Giedd JN, Clasen LS, Lenroot R, Greenstein D, Wallace GL, Ordaz S, Molloy EA, Blumenthal JD, Tossell JW, Stayer C, Samango-Sprouse CA, Shen D, Davatzikos C, Merke D, Chrousos GP. Puberty-related influences on brain development. Mol Cell Endocrinol. 2006 Jul 25; 254-255:154-62.
Kuroda S. Neuronal expression of cyclooxygenase-2, a pro-inflammatory protein, in the hippocampus of patients with schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2004 Jul; 28(4):715-21.
McGrath, J. The impact of low prenatal vitamin D on brain development: using an animal model to examine the vitamin D hypothesis of schizophrenia. Schizophrenia Research 2001. vol 49, p 48.
Mizui M, Kumanogoh A, Kikutani H. Immune semaphorins: novel features of neural guidance molecules. J Clin Immunol. 2009 Jan; 29(1):1-11. Epub 2008 Dec 6.
Muller N, Riedel M, Scheppach C, Brandstatter B, Sokullu S, Krampe K, Ulmschneider M, Engel RR, Moller HJ, Schwarz MJ. Beneficial antipsychotic effects of celecoxib add-on therapy compared to risperidone alone in schizophrenia. Am J Psychiatry. 2002 Jun;159(6):1029-34.
Muller N, Riedel M, Schwarz MJ, Engel RR. Clinical effects of COX-2 inhibitors on cognition in schizophrenia. Eur Arch Psychiatry Clin Neurosci. 2005 Apr; 255(2):149-51. Epub 2004 Nov 19.
Rapaport MH, Delrahim KK, Bresee CJ, Maddux RE, Ahmadpour O, Dolnak D. Celecoxib augmentation of continuously ill patients with schizophrenia. Biol Psychiatry. 2005 Jun 15; 57(12):1594-6.
Welham J. Climate, geography and the search for candidate nongenetic risk factors for schizophrenia Int Jour of Mental Health. 2000; 29: 79.
YB Cheung, KS Khoo, J Karlberg, D Machin. Association between psychological symptoms in adults and growth in early life: longitudinal follow up study. BMJ Volume. 2002 Oct 5; 325.
Pascalis O, Scott LS, Kelly DJ, Shannon RW, Nicholson E, Coleman M, Nelson CA. Plasticity of face processing in infancy. Proc Natl Acad Sci USA. 2005 Apr 5;102(14):5297-300.
Hertzman C. Commentary on the symposium: biological embedding, life course development, and the emergence of a new science. Annu Rev Public Health. 2013 Mar 18;34:1-5.
Caldji C, Diorio J, Meaney MJ. Variations in maternal care in infancy regulate the development of stress reactivity. Biol Psychiatry. 2000 Dec 15; 48(12):1164-74.
Douglas JW. Early hospital admissions and later disturbances of behaviour and learning. Dev Med Child Neurol. 1975 Aug; 17(4):456-80.
Fenoglio KA, Brunson KL, Avishai-Eliner S, Chen Y, Baram TZ. Region-specific onset of handling-induced changes in corticotropin-releasing factor and glucocorticoid receptor expression. Endocrinology. 2004 Jun; 145(6):2702-6. Epub 2004 Mar 24.
Francis D, Diorio J, Liu D, Meaney MJ. Nongenomic transmission across generations of maternal behavior and stress responses in the rat. Science. 1999 Nov 5; 286(5442):1155-8.
Landrigan PJ, Sonawane B, Butler RN, Trasande L, Callan R, Droller D. Early environmental origins of neurodegenerative disease in later life. Environ Health Perspect. 2005 Sep; 113(9):1230-3.
Liu D, Diorio J, Tannenbaum B, Caldji C, Francis D, Freedman A, Sharma S, Pearson D, Plotsky PM, Meaney MJ. Maternal care, hippocampal glucocorticoid receptors, and hypothalamic-pituitary-adrenal responses to stress. Science. 1997 Sep 12; 277(5332):1659-62.
Meaney MJ. Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations. Annu Rev Neurosci. 2001; 24:1161-92.
Weaver IC, Meaney MJ, Szyf M. Maternal care effects on the hippocampal transcriptome and anxiety-mediated behaviors in the offspring that are reversible in adulthood. Proc Natl Acad Sci USA. 2006 Feb 28; 103(9):3480-5.
Knutsen AK, Chang YV, Grimm CM, Phan L, Taber LA, Bayly PV. A new method to measure cortical growth in the developing brain. J Biomech Eng. 2010 Oct;132(10):101004.
O'Donnell S, Noseworthy MD, Levine B, Dennis M. Cortical thickness of the frontopolar area in typically developing children and adolescents. Neuroimage. 2005 Feb 15; 24(4):948-54. Epub 2004 Dec 15.
Shaw P, Greenstein D, Lerch J, Clasen L, Lenroot R, Gogtay N, Evans A, Rapoport J, Giedd J. Intellectual ability and cortical development in children and adolescents. Nature. 2006 Mar 30; 440(7084):676-9.
Moberg PJ, Roalf DR, Gur RE, Turetsky BI. Smaller nasal volumes as stigmata of aberrant neurodevelopment in schizophrenia. Am J Psychiatry. 2004 Dec; 161(12):2314-6.
Turetsky BI, Moberg PJ, Arnold SE, Doty RL, Gur RE. Low olfactory bulb volume in first-degree relatives of patients with schizophrenia. Am J Psychiatry. 2003 Apr; 160(4):703-8.
Klimek V, Zhu MY, Dilley G, Konick L, Overholser JC, Meltzer HY, May WL, Stockmeier CA, Ordway GA. Effects of long-term cigarette smoking on the human locus coeruleus. Arch Gen Psychiatry 2001 Sep; 58(9):821-7.
Kemper KJ, Khirallah M. Acute Effects of Online Mind-Body Skills Training on Resilience, Mindfulness, and Empathy. J Evid Based Complementary Altern Med. 2015 Mar 17.
Abraham, C. Is there a geek syndrome? The Globe and Mail. Saturday, October 19, 2002.
Basco, William T. Communication, Cognition Problems in Children with Autistic Siblings Medscape Pediatrics. 2007; Posted 08/06/2007.
Misery L, Rousset H. [Is alopecia areata a psychosomatic disease?] Rev Med Interne. 2001 Mar; 22(3):274-9. [Article in French]
Schore, AN. Affect dysregulation and disorders of the self. W.W. Norton & Co., 2003.
Sherman, C. Localizing the unconscious: look in the right brain. Clin Psyc News. 1998; 26(12):5.
Stone WL, McMahon CR, Yoder PJ, Walden TA. Early social-communicative and cognitive development of younger siblings of children with autism spectrum disorders. Arch Pediatr Adolesc Med. 2007; 161:384-390.
Vanheule S, Desmet M, Meganck R, Bogaerts S. Alexithymia and interpersonal problems. J Clin Psychol. 2007 Jan; 63(1):109-17.
Haraguchi T, Ishizu H, Terada S, Takehisa Y, Tanabe Y, Nishinaka T, Kawai K, Kuroda S, Komoto Y, Namba M. An autopsy case of postencephalitic parkinsonism of von economo type: some new observations concerning neurofibrillary tangles and astrocytic tangles. Neuropathology. 2000 Jun; 20(2):143-8.
Willemsen R, Roseeuw D, Vanderlinden J. Alexithymia and dermatology: the state of the art. Int J Dermatol. 2008 Sept; 47(9):903-10.
Ghourchian S, Bahrami P. The higher prevalence of non-right handers among patients with restless leg syndrome. Neurol Sci. 2014 Dec;35(12):1909-13.
Akgun A, Okuyan O, Baytan SH, Topbas M. Relationships between nonverbal IQ and brain size in right and left-handed men and women. Int J Neurosci. 2003 Jul; 113(7):893-902.
Benbow CP. Physiological correlates of extreme intellectual precocity. Neuropsychologia. 1986; 24(5):719-25.
Coren S. Handedness and allergic response. Int J Neurosci. 1994 Jun; 76(3-4):231-6.
Geschwind N, Behan P. Left-handedness: association with immune disease, migraine, and developmental learning disorder. Proc Natl Acad Sci USA. 1982 Aug; 79(16):5097-100.
Lawrence C. Wood, David S. Cooper. Autoimmune thyroid disease, left-handedness, and developmental dyslexia. Psychoneuroendocrinology. 1992 Mar; 17(1):95-99.
Martino G, Winner E. Talents and disorders: relationships among handedness, sex, and college major. Brain Cogn. 1995 Oct; 29(1):66-84.
Morfit NS, Weekes NY. Handedness and immune function. Brain Cogn. 2001 Jun-Jul; 46(1-2):209-13.
O'Callaghan MJ, Burn YR, Mohay HA, Rogers Y, Tudehope DI. The prevalence and origins of left hand preference in high risk infants, and its implications for intellectual, motor and behavioural performance at four and six years. Cortex. 1993 Dec; 29(4):617-27.
Pennington BF, Smith SD, Kimberling WJ, Green PA, Haith MM. Left-handedness and immune disorders in familial dyslexics. Arch Neurol. 1987 Jun; 44(6):634-9.
Smith J. Left-handedness: its association with allergic disease. Neuropsychologia. 1987; 25(4):665-74.
Tan U. Manual proficiency in Cattel's Intelligence Test in left-handed male and female subjects. Int J Neurosci. 1989 Jan; 44(1-2):17-26.
Wampold CH. Redesigning fraternal birth order studies from top to bottom. Arch Sex Behav. 2013 Nov;42(8):1387-9.
Brown, WM, Hines M. Fane BA. Breedlove, SM. Masculinized finger-length patterns in human males and females with congenital adrenal hyperplasia. Hormones and Behavior. 2002; 42:380–386.
Puts DA, Jordan CL, Breedlove SM. O brother, where art thou? The fraternal birth-order effect on male sexual orientation. Proc Natl Acad Sci USA. 2006 Jul 11; 103(28):10531-2.
Gender spectrum http://www.genderspectrum.org/
Gold C. The Intersex Spectrum. Nova
Smolderen KG, Strait KM, Dreyer RP), D'Onofrio G, et al. Depressive Symptoms in Younger Women and Men Insights From the VIRGO Study. J Am Heart Assoc. 2015 Apr 2;4(4).
Hudson, Christopher G. Socioeconomic Status and Mental Illness: Tests of the Social Causation and Selection Hypotheses Am Journ of Orthopsychiatry. 75(1).
Chiu S, Wegelin JA, Blank J, Jenkins M, Day J, Hessl D, Tassone F, Hagerman R. Early acceleration of head circumference in children with fragile x syndrome and autism. J Dev Behav Pediatr. 2007 Feb; 28(1):31-5.
Cynader, MS, & Frost, BJ. Mechanisms of brain development: Neuronal sculpting by the physical and social environment. In D. P. Keating & C. Hertzman (Eds.) Developmental health and the wealth of nations: social, biological, and educational dynamics. New York: Guilford Press, 1999.
Dewaraja R, Sasaki Y. A left to right hemisphere callosal transfer deficit of nonlinguistic information in alexithymia. Psychother Psychosom. 1990; 54(4):201-7.
Grandin, Temple. Genius ,may be an abnormality: educating students with asperger's syndrome or high functioning autism.
Kouprina N, et al. Accelerated evolution of the ASPM gene controlling brain size begins prior to human brain expansion. PLoS Biol. 2004 May; 2(5):E126. Epub 2004 Mar 23.
Landrigan PJ, Sonawane B, Butler RN, Trasande L, Callan R, Droller D. Early environmental origins of neurodegenerative disease in later life. Environ Health Perspect. 2005 Sep; 113(9):1230-3.
Reynolds MD, Johnston JM, Dodge HH, DeKosky ST, Ganguli M. Small head size is related to low Mini-Mental State Examination scores in a community sample of nondemented older adults. Neurology. 1999 Jul 13; 53(1):228-9.
Jaremka LM, Glaser R, Malarkey WB, Kiecolt-Glaser JK. Marital distress prospectively predicts poorer cellular immune function. Psychoneuroendocrinology. 2013 Nov;38(11):2713-9.
A bright future for PNI: Psychologists' work in the field of psychoneuroimmunology is expanding the understanding of how psychosocial factors can protect or damage our health. Monitor on Psychology. 2002 June 6. 33(6).
Kiecolt-Glaser JK, Bane C, Glaser R, Malarkey WB. Love, marriage, and divorce: newlyweds' stress hormones foreshadow relationship changes. J Consult Clin Psychol. 2003 Feb; 71(1):176-88.
Severance EG, Prandovszky E, Castiglione J, Yolken RH. Gastroenterology issues in schizophrenia: why the gut matters. Curr Psychiatry Rep. 2015 May;17(5):574.
Lanquillon S, Krieg J, Bening-Abu-Shach U, Vedder H. Cytokine production and treatment response in major depressive disorder. Neuropsychopharmacology. 2000 Apr 1; 22(4):370-379.
Reference: John J. Spollen III, MD Inflammatory Processes in Mental Illness Medscape
Huerta PT, Kowal C, DeGiorgio LA, Volpe BT, Diamond B. Immunity and 103(3):678-83.
McDonough E, Ayearst R, Eder L, Chandran V, Rosen CF, Thavaneswaran A, Gladman Depression and anxiety in psoriatic disease: prevalence and associated factors. J Rheumatol. 2014 May;41(5):887-96.
Azad N, Gondal M, Abbas N. Frequency of depression and anxiety in patients attending a rheumatology clinic. J Coll Physicians Surg Pak. 2008 Sep;18(9):569-73.
Irwin MR, Davis M, Zautra A. Behavioral Comorbidities in Rheumatoid Arthritis: A Psychoneuroimmunological Perspective. Psychiatr Times. 2008 Aug 1;25(9):1.
Vroomen-Durning, M. Rheumatoid Arthritis and Your Mental Health. Everyday Health 2010.
Uguz F, Akman C, Kucuksarac S, Tufekci O. Anti-tumor necrosis factor-alpha therapy is associated with less frequent mood and anxiety disorders in patients with rheumatoid arthritis. Psychiatry Clin Neurosci. 2009 Feb;63(1):50-5.
Uguz F(1), Kucuk A, Cicek E, Kayhan F, Tunc R. Mood, anxiety and personality disorders in patients with systemic lupus erythematosus. Compr Psychiatry. 2013 May;54(4):341-5.
Ampelas JF, Wattiaux MJ, Van Amerongen AP. [Psychiatric manifestations of lupus erythematosus systemic and Sjogren's syndrome] Encephale. 2001 Nov-Dec; 27(6):588-99. [Article in French]
Hanly JG. Neuropsychiatric lupus. Rheum Dis Clin North Am. 2005 May; 31(2):273-98, vi.
Hopkinson ND, Bendall P, Powell RJ. Screening of acute psychiatric admissions for previously undiagnosed systemic lupus erythematosus. Br J Psychiatry. 1992 Jul; 161:107-10.
Kowal C, Degiorgio LA, Lee JY, Edgar MA, Huerta PT, Volpe BT, Diamond B. Human lupus autoantibodies against NMDA receptors mediate cognitive impairment. Proc Natl Acad Sci USA. 2006 Dec 26; 103(52): 19854-9.
Miguel Filho EC, Pereira RM, de Almeida OP, Hirsch R, Lafer B, Fang T, Busatto Filho G, de Arruda PC. [Neuropsychiatric disorders in systemic lupus erythematosus: a multidisciplinary review] Rev Paul Med. 1990 Jul-Aug; 108(4):174-82. [Article in Portuguese]
Weiner SM, Peter HH. [Neuropsychiatric involvement in systemic lupus erythematosus. Part 1: clinical presentation and pathogenesis] Med Klin (Munich). 2002 Dec 15; 97(12):730-7. [Article in German]
Pelizza L, Bonacini F, Ferrari A. Psychiatric disorder as clinical presentation of primary Sjögren's syndrome: two case reports. Ann Gen Psychiatry. 2010 Apr 1;9:12.
Cox PD, Hales RE. CNS Sjögren's syndrome: an underrecognized and underappreciated neuropsychiatric disorder. J Neuropsychiatry Clin Neurosci. 1999 Spring;11(2):241-7.
Moore, Elaine. Sjogren's Syndrome: Psychiatric Symptoms in Rheumatological Disorders. Suite 101. Jan 3, 2008. [Accessed Sept 7, 2010.]
Spezialetti R, Bluestein HG, Peter JB, Alexander EL. Neuropsychiatric disease in Sjögren's syndrome: anti-ribosomal P and anti-neuronal antibodies. Am J Med. 1993 Aug;95(2):153-60.
Tarter RE, Hays AL, Carra J, Edwards KL, Van Thiel DH. Sjogren's syndrome. Its contribution to neuropsychiatric syndrome in patients with primary biliary cirrhosis. Dig Dis Sci. 1989 Jan;34(1):9-12.
Neves N, Santos L, Reis C, Sarmento A. Candida albicans brain abscesses in an injection drug user patient: a case report. BMC Res Notes. 2014 Nov 25;7:837.
Irving G, Miller D, Robinson A, Reynolds S, Copas AJ. Psychological factors associated with recurrent vaginal candidiasis: a preliminary study. Sex Transm Infect. 1998 Oct; 74(5):334-8.
Jacobsen S, Bryhni IL, Gjermo P. Oral candidosis – frequency, treatment and relapse tendency in a group of psychiatric inpatients. Acta Odontol Scand. 1979; 37(6):353-61.
Aran A, et al. Elevated anti-streptococcal antibodies in patients with recent narcolepsy onset. Sleep. 2009 Aug 1; 32(8):979-83.
Bodner SM, Morshed SA, Peterson BS. The question of PANDAS in adults. Biol Psychiatry. 2001 May 1; 49(9):807-10.Henry MC, Perlmutter SJ, Swedo SE. Anorexia, OCD, and streptococcus. J Am Acad Child Adolesc Psychiatry. 1999 Mar; 38(3):228-9.
Perlmutter SJ, Leitman SF, Garvey MA, Hamburger S, Feldman E, Leonard HL, Swedo SE. Therapeutic plasma exchange and intravenous immunoglobulin for obsessive-compulsive disorder and tic disorders in childhood. Lancet. 1999 Oct 2; 354(9185):1153-8.
Wormser GP, Weitzner E, McKenna D, Nadelman RB, Scavarda C, Nowakowski J. Long-term Assessment of Fatigue in Patients with Culture-confirmed Lyme Disease. Am J Med. 2015. Feb;128(2):181-4.
Fallon, BA. Nields, JA. Lyme Disease: A Neuropsychiatric Illness Am J Psychiatry. 1994 Nov; 151(11): 1571-1580.
Kaplan, RF. Applied Neuropsychology: Special Issue: Neuropsychological Aspects of Lyme Disease. Lawrence Erlbaum Associates, 1999.
[No authors cited] Overview of Neuropsychiatric Lyme Disease. Columbia University Medical Center.
Da R, Ren JK. [Pathogenic significance and possible pathogenic mechanism of human endogenous viruses in development of schizophrenia]. . Bing Du Xue Bao. 2014 Jan;30(1):98-102.
Lipkin WI, Briese T, Hornig M. Borna disease virus - fact and fantasy. Virus Res. 2011 Dec;162(1-2):162-72.
Bode L, Durwald R, Rantam FA, et al: First isolation of infectious human Borna disease virus from patients with mood disorders. Mol Psychiatry. 1996; 1:200-212.
Bode L, Zimmermann W, Ferszt R, et al. Borna disease virus genome transcribed and expressed in psychiatric patients. Nat Med. 1996; 1:232-236.
Dickerson FB, Boronow JJ, Stallings C, Origoni AE, Cole S, Krivogorsky B, Yolken RH. Infection with herpes simplex virus type 1 is associated with cognitive deficits in bipolar disorder. Biol Psychiatry. 2004 Mar 15; 55(6):588-93.
Ferszt R, et al. Amantadine revisited: an open trial of amantadinesulfate treatment in chronically depressed patients with Borna disease virus infection. Pharmacopsychiatry. 1999 Jul; 32(4):142-7.
Sauder C, et al., Detection of Borna disease virus (BDV) antibodies and Wolke D. Psychosocial adversity and growth during infancy. [Accessed October 1, 2006]
Sauder C, et al. Detection of Borna disease virus (BDV) antibodies and BDV RNA in psychiatric patients: evidence for high sequence conservation of human blood-derived BDV RNA. J Virol. 1996 Nov; 70(11):7713-24.
Waltrip RW 2nd, et al., Borna disease virus and schizophrenia. Psychiatry Res. 1995 Jan 31; 56(1):33-44.
Jonker I, Klein HC, Duivis HE, Yolken RH, Rosmalen JG, Schoevers RA. Association between exposure to HSV1 and cognitive functioning in a general population of adolescents. The TRAILS study. PLoS One. 2014 Jul 1;9(7):e101549.
Dickerson FB, Boronow JJ, Stallings C, Origoni AE, Cole S, Krivogorsky B, Yolken RH. Infection with herpes simplex virus type 1 is associated with cognitive deficits in bipolar disorder. Biol Psychiatry. 2004 Mar 15; 55(6):588-93.
Carlson MD, Hilsabeck RC, Barakat F, Perry W. Role of Sleep Disturbance in Chronic Hepatitis C Infection. Curr Hepat Rep. 2010 Feb;9(1):25-29.
Erim Y, Tagay S, Beckmann M, Bein S, Cicinnati V, Beckebaum S, Senf W, Schlaak JF. Depression and protective factors of mental health in people with hepatitis C: a questionnaire survey. Int J Nurs Stud. 2010 Mar;47(3):342-9.
Falasca K, Mancino P, Ucciferri C, Dalessandro M, Manzoli L, Pizzigallo E, Conti CM, Vecchiet J. Quality of life, depression, and cytokine patterns in patients with chronic hepatitis C treated with antiviral therapy. Clin Invest Med. 2009 Jun 1;32(3):E212-8.
Geoffrey Cowley Hepatitis C: The Insidious Spread of a Killer Virus. This Stealthy Disease Can Incubate For Decades. Now Thousands Of People Are Getting Sick. By 2010 It May Strike Down More Americans Each Year Than Aids. Newsweek Apr 22, 2002.
Hager, M. Reibstein, L. Do You Have Hepatitis C? Nearly 4 Million Americans Are Infected. Most Don't Know It. Newsweek May 4, 1998.
Huckans M, Mitchell A, Pavawalla S, Morasco BJ, Ruimy S, Loftis JM, Rifai MA, Hauser P. The influence of antiviral therapy on psychiatric symptoms among patients with hepatitis C and schizophrenia. Antivir Ther. 2010;15(1):111-9.
Mamani M, Hashemi SH, Niayesh A, Ghaleiha A, Hajilooei M. Study on the frequency of hepatitis B and C infection in chronic psychiatric patients in Hamedan in 2006-2007. J Pak Med Assoc. 2009 Aug;59(8):505-7.
Rifai MA, MD. Rosenstein DL, MD. Hepatitis C and psychiatry. Focus. 2005; 3:194-202.
Kraft R. Cysticercosis: an emerging parasitic disease. Am Fam Physician. 2007 Jul 1; 76(1):91-6.
Trivedi JK, Singh RK, Dalal, PK. Psychiatric manifestations of cysticercosis: review of literature and case report. Indian J of Psychiatry. 1983; 25:74-77.
Forlenza OV, et al. Psychiatric manifestations of neurocysticercosis: a study of 38 patients from a neurology clinic in Brazil. J Neurol Neurosurg Psychiatry. 1997 Jun; 62(6):612-6.
DeGiorgio CM, Medina MT, Durón R, Zee C, Escueta SP. Neurocysticercosis. Epilepsy Curr. 2004 May-Jun; 4(3):107-11.
Fabiani S, Pinto B, Bonuccelli U, Bruschi F. Neurobiological studies on the relationship between toxoplasmosis and neuropsychiatric diseases. J Neurol Sci. 2015 Feb 21.
Berdoy M, Webster JP, Macdonald DW. Fatal attraction in rats infected with toxoplasma gondii. Proc. Biol. Sci. 2000 Aug; 267(1452):1591–4.
Flegr J, Klose J, Novotná M, Berenreitterová M, Havlíček J. Increased incidence of traffic accidents in toxoplasma-infected military drivers and protective effect RhD molecule revealed by a large-scale prospective cohort study. BMC Infectious Diseases. 2009; 9(72):72.
Flegr J. Effects of toxoplasma on human behavior. Schizophr Bull. 2007 May; 33(3):757-60. Epub 2007 Jan 11.
Holliman RE, Toxoplasmosis, behaviour and personality. J Infect. 1997;35:105–110.
Webster JP, Rats, cats, people and parasites: the impact of latent toxoplasmosis on behaviour. Microbes Infect. 2001; 3:1037–1045.
do Nascimento SN, Barth A, Göethel G, Baierle M. Cognitive deficits and ALA-D-inhibition in children exposed to multiple metals. Environ Res. 2015 Jan;136:387-95.
Weiss, B. Psychological indices of toxicity. 2005. In: Wexler, P. Encyclopedia of Toxicology (2nd edition). Oxford, Elsevier, 558-567.
Nunes E(1), Cavaco A, Carvalho C. Children's health risk and benefits of fish consumption: risk indices based on a diet diary follow-up of two weeks. J Toxicol Environ Health A. 2014;77(1-3):103-14.
Pereira P, Raimundo J, Barata M, Araújo O, et al. A new page on the road book of inorganic mercury in fish body – tissue distribution and elimination following waterborne exposure and post-exposure periods. Metallomics. 2015 Feb 13.
Bemis JC, Seegal RF. Polychlorinated biphenyls and methylmercury act synergistically to reduce rat brain dopamine content in vitro. Environ Health Perspect. 1999 Nov; 107(11):879-85.
Haut MW, Morrow LA, Pool D, Callahan TS, Haut JS, Franzen MD. Neurobehavioral effects of acute exposure to inorganic mercury vapor. Appl Neuropsychol. 1999; 6(4):193-200.
Laks DR. Assessment of chronic mercury exposure within the U.S. population, National Health and Nutrition Examination Survey, 1999-2006. Biometals. 2009 Aug 21.
Pendergrass JC, et al. Mercury vapor inhalation inhibits binding of GTP to tubulin in rat brain: similarity to a molecular lesion in Alzheimer diseased brain. Neurotoxicol. 1997;18(2):315-324.
Weiss, B. Psychological indices of toxicity. In: Wexler, P. Encyclopedia of Toxicology (2d ed). Oxford, Elsevier: 2005.
Windham B. (Ed.) Mercury-caused endocrine conditions causing widespread adverse health effects, cognitive effects, and fertility effects. [Accessed 2010]
Mercury: Human exposure. http://www.epa.gov/ earlink1/mercury/ exposure.htm [Accessed 2010]
Siblerud RL, Motl J, Kienholz E. Psychometric evidence that mercury from silver dental fillings may be an etiological factor in depression, excessive anger, and anxiety. Psychol Rep. 1994 Feb; 74(1):67-80.
Siblerud RL, Kienholz E. Evidence that mercury from silver dental fillings may be an etiological factor in multiple sclerosis. Sci Total Environ. 1994 Mar 15; 142(3):191-205.
Zhang Z, Guo G, Teng Y, Wang J, Rhee JS, Wang S, Li F. Screening and assessment of solidification/stabilization amendments suitable for soils of lead-acid battery contaminated site. J Hazard Mater. 2015 May 15;288:140-6.
Bleecker ML, Ford DP, Lindgren KN, Hoese VM, Walsh KS, Vaughan CG. Differential effects of lead exposure on components of verbal memory. Occup Environ Med. 2005 Mar; 62(3):181-7.
Kuhnlein HV, Calloway DH. Minerals in human teeth: differences between pre-industrial and contemporary Hopi Indians. Am J Clin Nutr. 1977 Jun; 30(6):883-6.
Morrow L, Needleman HL, McFarland C, Metheny K, Tobin M. Past occupational exposure to lead: association between current blood lead and bone lead. Arch Environ Occup Health. 2007 Winter; 62(4):183-6.
Muldoon SB, Cauley JA, Kuller LH, Morrow L, Needleman HL, Scott J, Hooper FJ. Effects of blood lead levels on cognitive function of older women. Neuroepidemiology. 1996; 15(2):62-72.
Needleman HL, Riess JA, Tobin MJ, Biesecker GE, Greenhouse JB. Bone lead levels and delinquent behavior. JAMA. 1996 Feb 7; 275(5):363-9.
Needleman HL, McFarland C, Ness RB, Fienberg SE, Tobin MJ. Bone lead levels in adjudicated delinquents: a case control study. Neurotoxicol Teratol. 2002 Nov-Dec; 24(6):711-7.
Nevin R. How lead exposure relates to temporal changes in IQ, violent crime, and unwed pregnancy. Environ Res. 2000 May; 83(1):1-22.
Roberts JW, Wallace LA, Camann DE, Dickey P, Gilbert SG, Lewis RG, Takaro TK. Monitoring and reducing exposure of infants to pollutants in house dust. Rev Environ Contam Toxicol. 2009; 201:1-39.
Stretesky PB, Lynch MJ. The relationship between lead exposure and homicide. Arch Pediatr Adolesc Med. 2001 May; 155(5):579-82.
Wacker, John. Air lead concentrations, homicide rates linked. Crime Times. 2001; 7(3):1.
Mariano C, Palmela I, Pereira P, Fernandes A, at al. Tricellulin expression in brain endothelial and neural cells. Cell Tissue Res. 2013 Mar;351(3):397-407.
Cresta L, Perdelli F, Franco Y, Raffo E, Cristina ML, Diani F. [Possible correlations between urinary cadmium and fetal growth retardation in pregnant women who smoke] Minerva Ginecol. 1989 Feb; 41(2):85-8.
Holloway WR Jr, Thor DH. Cadmium exposure in infancy: effects on activity and social behaviors of juvenile rats. Neurotoxicol Teratol. 1988 Mar-Apr; 10(2):135-42.
Ozden TA, et al. Elevated hair levels of cadmium and lead in school children exposed to smoking and in highways near schools. Clin Biochem. 2007 Jan; 40(1-2):52-6.
Schoeters G, et al. Cadmium and children: exposure and health effects. Acta Paediatr Suppl. 2006 Oct; 95(453):50-4.
Yorbik O, Kurt I, Haşimi A, Oztürk O. Chromium, cadmium, and lead levels in urine of children with autism and typically developing controls. Biol Trace Elem Res. 2009 Aug 18.
Anway MD, Cupp AS, Uzumcu M, Skinner MK. Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science. 2005 Jun 3; 308(5727):1466-9.
Wang A, Cockburn M, Ly TT, Bronstein JM, Ritz B. The association between ambient exposure to organophosphates and Parkinson's disease risk. Occup Environ Med. 2014 Apr;71(4):275-81.
Baldereschi M, Inzitari M, Vanni P, Di Carlo A, Inzitari D. Pesticide exposure might be a strong risk factor for Parkinson's disease. Ann Neurol. 2008 Jan; 63(1):128.
Beseler C, et al. Depression and pesticide exposures in female spouses of licensed pesticide applicators in the agricultural health study cohort. J Occup Environ Med. 2006 Oct; 48(10):1005-13.
Brown, TP. Rumsby, PC. Capleton, AC. Rushton, L. Levy LS. Pesticides and Parkinson's Disease: is there a link? Environmental Health Perspectives. 2006 Feb; 114(2).
Coghlan, A. Exposure to pesticides can cause Parkinson's. Special report from New Scientist. 26 May 2005. Print edition.
Gibbs Lois (Ed.) Poisoned schools: invisible threats, visible actions. Diane Pub Co., 2001. [Accessed 2010]
Jacobson JL, Jacobson SW. Prenatal exposure to polychlorinated biphenyls and attention at school age. J Pediatr. 2003 Dec; 143(6):780-8.
London L, Flisher AJ, Wesseling C, Mergler D, Kromhout H. Suicide and exposure to organophosphate insecticides: cause or effect? Am J Ind Med. 2005 Apr; 47(4):308-21.
Meeker JD, Ryan L, Barr DB, Hauser R. Exposure to nonpersistent insecticides and male reproductive hormones. Epidemiology. 2006 Jan; 17(1):61-8.
Petrovitch H, Ross GW, Abbott RD, Sanderson WT, Sharp DS, Tanner CM, Masaki KH, Blanchette PL, Popper JS, Foley D, Launer L, White LR. Plantation work and risk of Parkinson disease in a population-based longitudinal study. Arch Neurol. 2002 Nov; 59(11):1787-92.
Van den Berg, H. Secretariat of the Stockholm Convention. Global status of DDT and its alternatives for use in vector control to prevent disease. Stockholm Convention/United Nations Environment Programme. October 23, 2008.
Vreugdenhil HJ, Slijper FM, Mulder PG, Weisglas-Kuperus N. Effects of perinatal exposure to PCBs and dioxins on play behavior in Dutch children at school age. Environ Health Perspect. 2002 Oct; 110(10):A593-8.
Weiss B. Behavior as an early indicator of pesticide toxicity. Toxicol Ind Health. 1988 Sep; 4(3):351-60.
Axelson O, Hane M, Hogstedt C. A case-referent study on neuropsychiatric disorders among workers exposed to solvents. Scand J Work Environ Health. 1976 Mar; 2(1):14-20.
Indoor air facts No. 4 (revised): sick building syndrome (SBS). Environmental Protection Agency. [Accessed 2010]
Indoor air quality and pollution http://www.indoorpollution.com [Accessed 2010]
Carpets: http://www.holisticmed.com/carpet/ [Accessed 2010]
Sebõk B, Schneider I, Harangi F; Primary Care Paediatricians in Baranya County. Familiar and environmental factors influencing atopic dermatitis in the childhood. J Eur Acad Dermatol Venereol. 2006 Apr; 20(4):418-22.
Sick building syndrome. Medicine Online.
Yu J. Endocrine disorders and the neurologic manifestations. Ann Pediatr Endocrinol Metab. 2014 Dec;19(4):184-90.
Hope J. A review of the mechanism of injury and treatment approaches for illness resulting from exposure to water-damaged buildings, mold, and mycotoxins. Scientific World Journal. 2013 Apr 18;2013:767482.
Baldo JV, Ahmad L, Ruff R. Neuropsychological performance of patients following mold exposure. Appl Neuropsychol. 2002; 9(4):193-202.
Crago BR, Gray MR, Nelson LA, Davis M, Arnold L, Thrasher JD. Psychological, neuropsychological, and electrocortical effects of mixed mold, exposure. Arch Environ Health. 2003 Aug; 58(8):452-63.
Hardin BD, Kelman BJ, Saxon A. Adverse human health effects associated with molds in the indoor environment. J Occup Environ Med. 2003 May; 45(5):470-8.
Kilburn KH. Indoor mold exposure associated with neurobehavioral and pulmonary impairment: a preliminary report. Arch Environ Health. 2003 Jul; 58(7):390-8.
Gordon WA, et al. Cognitive impairment associated with toxigenic fungal exposure: a replication and extension of previous findings. Appl Neuropsychol. 2004; 11(2):65-74.
Gray MR, et al. Mixed mold mycotoxicosis: immunological changes in humans following exposure in water-damaged buildings. Arch Environ Health. 2003 Jul; 58(7):410-20.
Potera C. Molding a link to depression. Environ Health Perspect. 2007 Nov; 115(11):A536.
Shenassa ED, Daskalakis C, Liebhaber A, Braubach M, Brown M. Dampness and mold in the home and depression: an examination of mold-related illness and perceived control of one's home as possible depression pathways. Am J Public Health. 2007 Oct; 97(10):1893-9.
Coupland C, Hill T, Morriss R, Arthur A, Moore M, Hippisley-Cox J. Antidepressant use and risk of suicide and attempted suicide or self harm in people aged 20 to 64: cohort study using a primary care database. BMJ. 2015 Feb 18;350:h517.
Lu CY, Zhang F, Lakoma MD, Madden JM. et. al Changes in antidepressant use by young people and suicidal behavior after FDA warnings and media coverage: quasi-experimental study. BMJ. 2014 Jun 18;348:g3596.
Anxiety. Wrong Diagnosis. http://www.wrongdiagnosis.com/ sym/anxiety.htm [Accessed 2010]
Depression. Wrong Diagnosis. http://www.wrongdiagnosis.com /d/depression/ causes.htm [Accessed 2010]
Kenneth J. Bender, Pharm.D., M.A. New warning of depression with accutane could apply to other medications. Psychiatric Times. 1998 May 1;15(5).
Larson MJ, Miller K, Fleming KJ. Antidepressant medication use in private insurance health plans, 2002. Psychiatr Serv. 2006 Feb; 57(2):175.
Gschwandtner U, Aston J, Renaud S, Fuhr P. Pathologic gambling in patients with Parkinson's disease. Clin Neuropharmacol. 2001 May-Jun; 24(3):170-2.
Szarfman A, Doraiswamy PM, Tonning JM, Levine JG. Association between pathologic gambling and Parkinsonian therapy as detected in the Food and Drug Administration Adverse Event database. Arch Neurol. 2006 Feb; 63(2):299-300.
Smith DA. Psychiatric side effects of non-psychiatric drugs. S D J Med. 1991 Oct; 44(10):291-2.
Allen, FE. One man’s suffering spurs doctors to probe pesticide-drug link. The Wall Street Journal. October 14, 1991.
Douglas, J. Prescription drugs found in soil sludge used for lawns and gardens NewsTarget. October 10, 2006. http://www.naturalnews.com [Accessed 2010]
Adler LE, Sadja L, Wilets G. Cimetidine toxicity manifested as paranoia and hallucinations. Am J Psychiatry. 1980 Sep;137(9):1112-3.
Agarwal SK. Cimetidine and visual hallucinations. JAMA. 1978 Jul 21;240(3):214.
Britton ML, Waller ES. Central nervous system toxicity associated with concurrent use of triazolam and cimetidine. Drug Intell Clin Pharm. 1985 Sep;19(9):666-8.
Russell WL, Lopez LM. Cimetidine-induced mental status changes: case report and literature review. Am J Hosp Pharm. 1980 Dec; 37(12):1667-71.
Sonnenblick M, Rosin AJ, Weissberg N. Neurological and psychiatric side effects of cimetidine--report of 3 cases with review of the literature. Postgrad Med J. 1982 Jul;58(681):415-8.
Yudofsky SC, Ahern G, Brockman R. Agitation, disorientation, and hallucinations in patients on cimetidine: a report of three cases and literature review. Gen Hosp Psychiatry. 1980 Sep;2(3):233-6.
Frick, EA. Presence of pharmaceuticals in wastewater effluent and drinking water, Metropolitan Atlanta, Georgia. July-September 1999. Proceedings of the 2001 Georgia Water Resources Conference, Athens, Georgia. March 26-27, 2001. [Accessed 2010]
Kolpin, DE. Pharmaceuticals, hormones, and other organic wastewater contaminants in U.S. streams, 1999-2000: a national reconnaissance. Environmental Science & Technology. 2002;36(6): 1202-1211. [Accessed 2010]
Reynolds, KA. Pharmaceuticals in drinking water supplies. Water Conditioning & Purification Magazine. 2003 June; 45(6). http://www.wcponline.com/ column.cfm? T=T&ID=2199 [Accessed 2010]
Henann NE, Carpenter DU, Janda SM. Famotidine-associated mental confusion in elderly patients. Drug Intell Clin Pharm. 1988 Dec; 22(12):976-8.
Golomb BA, Kane T, Dimsdale JE. Severe irritability associated with statin cholesterol-lowering drugs. QJM. 2004 Apr; 97(4):229-35.
Golomb BA. Cholesterol and violence: is there a connection? Ann Intern Med. 1998 Mar 15;128(6):478-87.
Golomb BA, Stattin H, Mednick S. Low cholesterol and violent crime. J Psychiatr Res. 2000 Jul-Oct; 34(4-5):301-9.
Mauch DH, Nägler K, Schumacher S, Göritz C, Müller EC, Otto A, Pfrieger FW. CNS synaptogenesis promoted by glia-derived cholesterol. Science. 2001 Nov 9; 294(5545):1354-7.
Tatley M, Savage R. Psychiatric adverse reactions with statins, fibrates and ezetimibe: implications for the use of lipid-lowering agents. Drug Saf. 2007; 30(3):195-201.
Wagstaff LR, Mitton MW, Arvik BM, Doraiswamy PM. Statin-associated memory loss: analysis of 60 case reports and review of the literature. Pharmacotherapy. 2003 Jul; 23(7):871-80.
Choudhry MN, Soran H, Ziglam HM. Overuse and inappropriate prescribing of proton pump inhibitors in patients with Clostridium difficile-associated disease. QJM. 2008 Jun; 101(6):445-8.
Cunningham R, Dial S. Is over-use of proton pump inhibitors fuelling the current epidemic of Clostridium difficile-associated diarrhoea? J Hosp Infect. 2008 Sep; 70(1):1-6.
Trygstad TK, Christensen DB, Wegner SE, Sullivan R, Garmise JM. Analysis of the North Carolina long-term care polypharmacy initiative: a multiple-cohort approach using propensity-score matching for both evaluation and targeting. Clin Ther. 2009 Sep;31(9):2018-37.
Zurakowski T. The practicalities and pitfalls of polypharmacy. Nurse Pract. 2009 Apr;34(4):36-41; quiz 41-2.
Klein P, Rubinstein LJ. Benign symptomatic glial cysts of the pineal gland: a report of seven cases and review of the literature. J Neurol Neurosurg Psychiatry. 1989 Aug; 52(8):991-5.
Maurizi CP. Disorder of the pineal gland associated with depression, peptic ulcers, and sexual dysfunction. South Med J. 1984 Dec; 77(12):1516-8.
Halber, Deborah, Small melatonin dose may be all that's needed for better sleep. MIT Tech Talk. November 3, 1999 [Accessed September 23, 2006]
Zhdanova IV, Wurtman RJ, Morabito C, Piotrovska VR, Lynch HJ. Effects of low oral doses of melatonin, given 2-4 hours before habitual bedtime, on sleep in normal young humans. Sleep. 1996 Jun; 19(5):423-31.
Zhdanova IV, Wurtman RJ, Lynch HJ, Ives JR, Dollins AB, Morabito C, Matheson JK, Schomer DL. Sleep-inducing effects of low doses of melatonin ingested in the evening. Clin Pharmacol Ther. 1995 May; 57(5):552-8.
Amar AP, Weiss MH. Pituitary anatomy and physiology. Neurosurg Clin N Am. 2003 Jan; 14(1):11-23, v.
Szarfman A, Tonning JM, Levine JG, Doraiswamy PM. Atypical antipsychotics and pituitary tumors: a pharmacovigilance study. Pharmacotherapy. 2006 Jun; 26(6):748-58.
[No author cited] Antipsychotic drug may be linked to pituitary tumors. http://www.naturalnews.com Jul 13, 2006.
Rosack J. FDA assesses antipsychotic's link to certain tumors. Psychiatric News. 2005, Aug 5; 40(15). [Accessed October 18, 2006]
Tamler R, Lee AK, Lewis MS, Post KD. It's all in the head: insomnia and anxiety caused by thyrotropin-secreting pituitary adenoma. Thyroid. 2006 Mar;16(3):317-8.
Correia MF, Maria AT, Prado S, Limbert C. Neonatal thyrotoxicosis caused by maternal autoimmune hyperthyroidism. BMJ Case Rep. 2015 Mar 6;2015.
Joffe RT. The use of thyroid supplements to augment antidepressant medication. J Clin Psychiatry. 1998; 59 Suppl 5:26-31.
Placidi GP, et al. Prevalence of psychiatric disorders in thyroid disease patients. Neuropsychobiology. 1998 Nov; 38(4):222-5.
Rack SK, Makela EH. Hypothyroidism and depression: a therapeutic challenge. Ann Pharmacother. 2000; 34(10):1142-1145.
Sher, L. Thyroid hormones and seasonal mood change. Am J Psychiatry. 2001 Feb; 158:2.
Touks C. Mental illness in hypothyroid patients. Br J Psychiatry. 1964; 110:706-710.
Whybrow PC, PranRe AJ, Treadway CR: Mental changes accompanying thyroid gland dysfunction. Arch Gen Psych. 1969; 20:48-63.
Wood, LC. Cooper, DS. Autoimmune thyroid disease, left-handedness, and developmental dyslexia. Psychoneuroendocrinology. 1992 Mar; 17(1):95-99.
Degner D, Meller J, Bleich S, Schlautmann V, Rüther E. Affective disorders associated with autoimmune thyroiditis. J Neuropsychiatry Clin Neurosci. 2001 Fall; 13(4):532-3.
Müssig K, Bartels M, Gallwitz B, Leube D, Häring HU, Kircher T. Hashimoto's encephalopathy presenting with bipolar affective disorder. Bipolar Disord. 2005 Jun; 7(3):292-7.
Yalçin B, Tamer E, Toy GG, Oztas P, Alli N. Development of pemphigus vulgaris in a patient with vitiligo and Hashimoto's thyroiditis. J Endocrinol Invest. 2005 Jun; 28(6):558-60.
Mancardi MM, Fazzini F, Rossi A, Gaggero R. Hashimoto's encephalopathy with selective involvement of the nucleus accumbens: a case report. Neuropediatrics. 2005 Jun; 36(3):218-20.
Zettinig G, Weissel M, Flores J, Dudczak R, Vogelsang H. Dermatitis herpetiformis is associated with atrophic but not with goitrous variant of Hashimoto's thyroiditis. Eur J Clin Invest. 2000 Jan; 30(1):53-7.
Bunevicius R, Prange AJ Jr. Psychiatric manifestations of Graves' hyperthyroidism: pathophysiology and treatment options. CNS Drugs. 2006; 20(11):897-909.
Stern RA, Robinson B, Thorner AR, Arruda JE, Prohaska ML, Prange AJ Jr. A survey study of neuropsychiatric complaints in patients with Graves' disease. J Neuropsychiatry Clin Neurosci. 1996 Spring; 8(2):181-5.
Steinberg PI. A case of paranoid disorder associated with hyperthyroidism. Can J Psychiatry. 1994 Apr; 39 (3):153-6.
Suwalska A, Lacka K, Lojko D, Rybakowski JK. Quality of life, depressive symptoms and anxiety in hyperthyroid patients. Rocz Akad Med Bialymst. 2005; 50 Suppl 1:61-3.
Guan LJ, Wang X, Meng S, Shi LF, Jiang WJ et al. Increased IL-21/IL-21R expression and its proinflammatory effects in autoimmune thyroid disease. Cytokine. 2015 Apr;72(2):160-5.
Wang X, Liu H, Zhang Y, Li J, et al. Effects of isolated positive maternal thyroglobulin antibodies on brain development of offspring in an experimental autoimmune thyroiditis model. Thyroid. 2015 Mar 6.
Aarflot T, Bruusgaard D/ Association between chronic widespread musculoskeletal complaints in thyroid autoimmunity, results from a community survey. Scan J Prim Health Care. 1996; 14(2) 111-115.
Grabe HJ, Volzke H, Ludemann J, Wolff B, Schwahn C, John U, Meng W, Freyberger HJ. Mental and physical complaints in thyroid disorders in the general population. Acta Psychiatr Scand. 2005 Oct;112(4):286-93.
Wood LC, Cooper DS. Autoimmune thyroid disease, left-handedness, and developmental dyslexia. Psychoneuroendocrinology. 1992;17(1):95-9.
Biondi B, Palmieri EA, Klain M, Schlumberger M, Filetti S, Lombardi G. Subclinical hyperthyroidism: clinical features and treatment options. Eur J Endocrinol. 2005 Jan; 152(1):1-9.
Bommer M, Eversmann T, Pickardt R, Leonhardt A, Naber D. Psychopathological and neuropsychological symptoms in patients with subclinical and remitted hyperthyroidism. Klin Wochenschr. 1990 Jun 5; 68(11): 552-8.
Bowen, R. Thyroid Hormones Pregnancy and Fetal Development. October 4, 1999.
Chueire VB, Romaldini JH, Ward LS. Subclinical hypothyroidism increases the risk for depression in the elderly. Arch Gerontol Geriatr. 2007 Jan-Feb; 44(1):21-8.
Morocco M, Kloos R. Subclinical hypothyroidism in women: who to treat. Clinical Journal of Women’s Health. 2000; 1(1):39-45.
Roquer J, Cano JF. Carpal tunnel syndrome and hyperthyroidism: a prospective study. Acta Neurol Scand. 1993 Aug; 88(2):149-52.
Shrier, DK. Burman, KD. Subclinical hyperthyroidism: controversies in management. Am Fam Physician. 2002; 65:431-8.
Surks MI, Ortiz E, Daniels GH, Sawin CT, Col NF, Cobin RH, Franklyn JA, Hershman JM, Burman KD, Denke MA, Gorman C, Cooper RS, Weissman NJ. Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA. 2004 Jan 14; 291(2):228-38.
Wartofsky L, Dickey RA. The evidence for a narrower thyrotropin reference range is compelling. J Clin Endocrinol Metab. 2005 Sep;90(9):5483-8.
[No author cited] Hidden Hyperthyroidism British Medical Journal, Vol. 4, No. 5732 Nov. 14, 1970, p. 386.Brenner I. Apathetic hyperthroidism. J Clin Psychiatry. 1978 May;; 39(5):479-80.
Eales, M. J., & van der Merwe, P. Severe apathetic hyperthyroidism with normal thyroid hormone levels.: British Journal of Psychiatry. 1995.
Gaitonde DY, Kepchar J, Sartori R, Sarkar M. Painless thyroiditis presenting as apathetic hyperthyroidism in a young male. Mil Med. 2008 Jun;; 173(6):609-11.
Grewal RP. Apathetic hyperthyroidism in an adolescent. J Psychiatry Neurosci. 1993 Nov; 18(5):276.
Lampe IK, Heeren TJ. Is apathy in late-life depressive illness related to age-at-onset, cognitive function, or vascular risk? Int Psychogeriatr. 2004; 16:481-486.
Marin RS. Apathy: a neuropsychiatric syndrome. J Neuropsychiatry Clin Neurosci. 1991 Summer; 3(3):243-54.
Palacios A, Cohen MA, Cobbs R: Apathetic Hyperthyroidism in Middle Age. International Journal of Psychiatry in Medicine 1991; 21(4):393‑400.
Sherman C. Long-Term SSRI use tied to apathy syndrome. OB/GYN News, May 1, 2001.
Stephenson, M. Should apathy be included in the DSM-5? Neuropsychiatry Reviews. 2005; 6(3).
Bahemuka M, Hodkinson HM. Screening for hypothyroidism in elderly inpatients. Br Med J. 1975 Jun 14; 2(5971):601-3.
Bauer M. High-dose thyroxine in prophylaxis resistant affective disorder. Biol Psychiatry. 1997; 42:1S-2975.
Constant, EL. Adam, S. Seron, X. Bruyer, R. Seghers, A. Daumerie C. Anxiety and depression, attention, and executive functions in hypothyroidism. J Intl Neuropsychological Soc. 2005; 11(5):535.Gaby AR. Sub-laboratory hypothyroidism and the empirical use of Armour thyroid. Altern Med Rev. 2004 Jun; 9(2):157-179.
Gunnarsson T, Sjöberg S, Eriksson M, Nordin C. Depressive symptoms in hypothyroid disorder with some observations on biochemical correlates. Neuropsychobiology. 2001; 43(2):70-74.
Howdeshell KL. A model of the development of the brain as a construct of the thyroid system. Environ Health Perspect. 2002 Jun; 110 Suppl 3:337-48.
Loaquin AM, MD, Osterweil D, MD, CMD, Sultzer, D, MD. The utility of the Mini Mental State Examination (MMSE) in identifying hypothyroid-induced cognitive impairment in the elderly. Nursing Home Medicine. 1997 June; 5(7).
Muthukrishnan J, Harikumar KV, Verma A, Modi K. Central hypothyroidism. Indian J Pediatr. 2010 Jan;77(1):94-6.
Pezzino V, Sipione C, Vigneri R. Improving the diagnosis of central hypothyroidism. J Endocrinol Invest. 2008 Oct;31(10):939.
Prieto-Tenreiro A, Diaz-Guardiola P. Isolated idiopathic central hypothyroidism in an adult, possibly caused by thyrotropin releasing hormone (TRH) deficiency. Hormones (Athens). 2010 Apr-Jun;9(2):176-80.
Waise A, Belchetz PE. Lesson of the week: unsuspected central hypothyroidism. BMJ. 2000 Nov 18; 321 (7271):1275-7.
Yamada M, Mori M. Mechanisms related to the pathophysiology and management of central hypothyroidism. Nat Clin Pract Endocrinol Metab. 2008 Dec;4(12):683-94. Epub 2008 Oct 21.
Chueire VB, Romaldini JH, Ward LS. Subclinical hypothyroidism increases the risk for depression in the elderly. Arch Gerontol Geriatr. 2007 Jan-Feb;44(1):21-8. Epub 2006 May 5.
Gulseren S, Gulseren L, Hekimsoy Z, Cetinay P, Ozen C, Tokatlioglu B. Depression, anxiety, health-related quality of life, and disability in patients with overt and subclinical thyroid dysfunction. Arch Med Res. 2006 Jan;37(1):133-9.
Kumar A, Chaturvedi PK, Mohanty BP. Hypoandrogenaemia is associated with subclinical hypothyroidism in men. Int J Androl. 2007 Feb;30(1):14-20.
Chakrabarti K, Singh PM, Joshi SP. Thyroid function in depression. Nepal Med Coll J. 2006 Mar;8(1):47-8.
Placidi GP, Boldrini M, Patronelli A, Fiore E, Chiovato L, Perugi G, Marazziti D. Prevalence of psychiatric disorders in thyroid diseased patients. Neuropsychobiology. 1998 Nov;38(4):222-5.
Rack SK, Makela EH. Hypothyroidism and depression: a therapeutic challenge. Ann Pharmacother. 2000 Oct;34(10): 1142-5.
Sinai C, Hirvikoski T, Vansvik ED, Nordström AL, Linder J, Nordström P, Jokinen J. Thyroid hormones and personality traits in attempted suicide. Psychoneuroendocrinology. 2009 Nov;34(10):1526-32. Epub 2009 Jun 13.
Suwalska A, Lacka K, Lojko D, Rybakowski JK. Quality of life, depressive symptoms and anxiety in hyperthyroid patients. Rocz Akad Med Bialymst. 2005;50 Suppl 1:61-3.
Blumberg KR, Mayer WJ, Parikh DK, Schnell LA. Liothyronine and levothyroxine in Armour thyroid. J Pharm Sci. 1987 Apr;76(4):346-7.
Bono G, Fancellu R, Blandini F, Santoro G, Mauri M. Cognitive and affective status in mild hypothyroidism and interactions with L-thyroxine treatment. Acta Neurol Scand. 2004 Jul;110(1):59-66.
Cooke RG, Joffe RT, Levitt AJ. T3 augmentation of antidepressant treatment in T4-replaced thyroid patients. J Clin Psychiatry 1992 Jan;53(1):16-8.
Joffe, R. T., Brimacombe, M., Levitt, A. J., Stagnaro-Green, A. (2007). Treatment of Clinical Hypothyroidism with Thyroxine and Triiodothyronine: A Literature Review and Metaanalysis. Psychosomatics 48: 379-384.
Gaby AR. Sub-laboratory hypothyroidism and the empirical use of Armour thyroid. Altern Med Rev. 2004 Jun;9(2):157-79.
Kaplan, M. M., Sarne, D. H., Schneider, A. B. (2003). In Search of the Impossible Dream? Thyroid Hormone Replacement Therapy That Treats All Symptoms in All Hypothyroid Patients. J. Clin. Endocrinol. Metab. 88: 4540-4542
van Harten AC, Leue C, Verhey FR. [Should depressive symptoms in patients with subclinical hypothyroidism be treated with thyroid hormone?] Tijdschr Psychiatr. 2008;50(8):539-43. [Article in Dutch]
Parathyroid.com [Accessed 2010]
Arlt W, Fremerey C, Callies F, Reincke M, Schneider P, Timmermann W, Allolio B. Well-being, mood and calcium homeostasis in patients with hypoparathyroidism receiving standard treatment with calcium and vitamin D. Eur J Endocrinol. 2002 Feb;146(2):215-22.
Bandyopadhyay SK, Moulick A, Chakrabarti N, Dutta A. Familial hypoparathyroidism. J Assoc Physicians India. 2010 Feb;58:115-7.
Lawlor BA. Hypocalcemia, hypoparathyroidism, and organic anxiety syndrome. J Clin Psychiatry. 1988 Aug;49(8):317-8.
Sitges-Serra A, Ruiz S, Girvent M, Manjón H, Dueñas JP, Sancho JJ. Outcome of protracted hypoparathyroidism after total thyroidectomy. Br J Surg. 2010 Aug 20. [Epub ahead of print]
Stelmasiak Z, Tarach JS, Nowicka-Tarach BM, Mitosek-Szewczyk K, Drop A. Idiopathic hypoparathyroidism with intracranial calcifications and dominant skin manifestations. Med Sci Monit. 2000 Jan-Feb;6(1):145-50.
Benge JF, Perrier ND, Massman PJ, Meyers CA, Kayl AE, Wefel JS. Cognitive and affective sequelae of primary hyperparathyroidism and early response to parathyroidectomy. J Int Neuropsychol Soc. 2009 Oct; 7:1-10.
Dieserud F, Brun AC, Låhne PE, Normann E. [Lithium treatment and hyperparathyroidism] Tidsskr Nor Laegeforen. 2001 Sep 20; 121(22):2602-3. [Article in Norwegian]
Driessen M, Wetterling T, Wedel T, Preuss R. Secondary hyperparathyroidism and depression in chronic renal failure. Nephron. 1995; 70(3):334-9.
Goyal A, Chumber S, Tandon N, Lal R, Srivastava A, Gupta S. Neuropsychiatric manifestations in patients of primary hyperparathyroidism and outcome following surgery. Indian J Med Sci. 2001 Dec; 55(12):677-86.
Hayabara T, Hashimoto K, Izumi H, Morioka E, Hosokawa K. Neuropsychiatric disorders in primary hyperparathyroidism. Jpn J Psychiatry Neurol. 1987 Mar; 41(1):33-40.
Joborn C, Hetta J, Lind L, Rastad J, Akerstrom G, Ljunghall S. Self-rated psychiatric symptoms in patients operated on because of primary hyperparathyroidism and in patients with long-standing mild hypercalcemia. Surgery. 1989 Jan;105(1):72-8.
Perrier, Nancy. The effect of parathyroidectomy on cognition and function in the elderly. The 2005 Dennis W. Jahnigen Scholars Career Development Abstracts.
Watson LC, Marx CE. New onset of neuropsychiatric symptoms in the elderly: possible primary hyperparathyroidism. Psychosomatics. 2002 Sep-Oct; 43(5):413-7.
Stancer HC, Forbath N. Hyperparathyroidism, hypothyroidism, and impaired renal function after 10 to 20 years of lithium treatment. Arch Intern Med. 1989 May;149(5):1042-5.
Rubin RT, Phillips JJ, Sadow TF, McCracken JT. Adrenal gland volume in major depression. Increase during the depressive episode and decrease with successful treatment. : Arch Gen Psychiatry. 1995 Mar;52(3):213-8.
Garside S, Rosebush PI, Levinson AJ, Mazurek MF. Late-onset adrenoleukodystrophy associated with long-standing psychiatric symptoms. J Clin Psychiatry. 1999 Jul;60(7):460-8.
Rosebush PI, Garside S, Levinson AJ, Mazurek MF. The neuropsychiatry of adult-onset adrenoleukodystrophy. J Neuropsychiatry Clin Neurosci. 1999 Summer;11(3):315-27.
Szpak GM, Lewandowska E, Schmidt-Sidor B, Popow J, Kozłowski P, Lechowicz W, Kulczycki J, Zaremba J, Dymecki J. Adult schizophrenic-like variant of adrenoleukodystrophy. Folia Neuropathol. 1996;34(4):184-92.
Warrington TP, Bostwick JM. Psychiatric adverse effects of corticosteroids. Mayo Clin Proc. 2006 Oct;81(10):1361-7.
Gold PW, et al. Psychiatric implications of basic and clinical studies with corticotropin-releasing factor. Am J Psychiatry. 1984 May; 141(5):619-27.
Nemeroff CB, Krishnan KR, Reed D, Leder R, Beam C, Dunnick NR. Adrenal gland enlargement in major depression: a computed tomographic study. Arch Gen Psychiatry. 1992 May; 49(5):384-7.
Rubin RT, Phillips JJ, Sadow TF, McCracken JT. Adrenal gland volume in major depression. Increase during the depressive episode and decrease with successful treatment. Arch Gen Psychiatry. 1995 Mar; 52(3):213-8.
Adams R, Hinkebein MK, McQuillen M, Sutherland S, El Asyouty S, Lippmann S. Prompt differentiation of Addison's disease from anorexia nervosa during weight loss and vomiting. South Med J. 1998 Feb;91(2):208-11.
Anglin RE, Rosebush PI, Mazurek MF. The neuropsychiatric profile of Addison's disease: revisiting a forgotten phenomenon. J Neuropsychiatry Clin Neurosci. 2006 Fall;18(4):450-9.
Iwata M, Hazama GI, Shirayama Y, Ueta T, Yoshioka S, Kawahara R. [A case of Addison's disease presented with depression as a first symptom] Seishin Shinkeigaku Zasshi. 2004;106(9):1110-6. [Article in Japanese]
Johnstone PA, Rundell JR, Esposito M. Mental status changes of Addison's disease. Psychosomatics. 1990 Winter;31(1):103-7.
Thomsen AF, Kvist TK, Andersen PK, Kessing LV. The risk of affective disorders in patients with adrenocortical insufficiency. Psychoneuroendocrinology. 2006 Jun;31(5):614-22. Epub 2006 Mar 20.
Mitchell L, Bellis F. Phaeochromocytoma--"the great mimic": an unusual presentation. Emerg Med J. 2007 Sep;24(9):672-3.
Platts JK, Drew PJ, Harvey JN. Death from phaeochromocytoma: lessons from a post-mortem survey. J R Coll Physicians Lond. 1995; 29:299-306.
Tisherman SE, Tisherman BG, Tisherman SA, Dunmire S, Levey GS, Mulvihill JJ.Three-decade investigation of familial pheochromocytoma. An allele of von Hippel-Lindau disease? Arch Intern Med. 1993 Nov 22;153(22):2550-6.
Yucha C, Blakeman N. Pheochromocytoma. The great mimic. Cancer Nurs. 1991 Jun;14(3):136-40.
Almeida OP, Yeap BB, Hankey GJ, Jamrozik K, Flicker L. Low free testosterone concentration as a potentially treatable cause of depressive symptoms in older men. Arch Gen Psychiatry. 2008 Mar;65(3): 283-9.
Braunstein GD. Androgen insufficiency in women: summary of critical issues. Fertil Steril. 2002 Apr; 77 Suppl 4:S94-9.
Carnahan RM, Perry PJ. Depression in aging men: the role of testosterone. Drugs Aging. 2004; 21(6):361-76.
Eskelinen SI, Vahlberg TJ, Isoaho RE, Kivelä SL, Irjala KM. Associations of sex hormone concentrations with health and life satisfaction in elderly men. Endocr Pract. 2007 Nov-Dec;13(7):743-9.
Goldstat R, Briganti E, Tran J, Wolfe R, Davis SR. Transdermal testosterone therapy improves well-being, mood, and sexual function in premenopausal women. Menopause. 2003 Sep-Oct; 10(5):390-8.
Gouin JP, Glaser R, Loving TJ, Malarkey WB, Stowell J, Houts C, Kiecolt-Glaser JK. Attachment avoidance predicts inflammatory responses to marital conflict. Brain Behav Immun. 2008 Oct 10.
Kalantaridou SN, Calis KA. Testosterone therapy in premenopausal women. Semin Reprod Med. 2006 Apr; 24(2):106-14.
Michael S. Bahrke, Charles E. Yesalis III, and James E. Wright. Psychological and behavioural effects of endogenous testosterone levels and anabolic-androgenic steroids among males: a review. Sports Medicine. 1990. 10(5) 303-337. [Accessed 2010]
Pope HG Jr, Cohane GH, Kanayama G, Siegel AJ, Hudson JI. Testosterone gel supplementation for men with refractory depression: a randomized, placebo-controlled trial. Am J Psychiatry. 2003 Jan;160(1):105-11.
Schweiger U, Deuschle M, Weber B, Korner A, Lammers CH, Schmider J, Gotthardt U, Heuser I. Testosterone, gonadotropin, and cortisol secretion in male patients with major depression. Psychosom Med 1999 May-Jun;61(3):292-6.
Seidman SN, Walsh BT. Testosterone and depression in aging men. Am J Geriatr Psychiatry 1999 Winter;7(1):18-33
Seidman SN, Rabkin JG. Testosterone replacement therapy for hypogonadal men with SSRI-refractory depression. J Affect Disord. 1998 Mar; 48(2-3):157-61.
Wang C, Alexander G, Berman N, Salehian B, Davidson T, McDonald V, Steiner B, Hull L, Callegari C, Swerdloff RS. Testosterone replacement therapy improves mood in hypogonadal men--a clinical research center study. J Clin Endocrinol Metab. 1996 Oct;81(10):3578-83.
Stahl, SM. Basic psychopharmacology of antidepressants, part 2: estrogen as an adjunct to antidepressant treatment. J Clin Psychiatry. 1998; 59 Suppl 4:15-24.
Rosack, J. Estrogen replacement doesn't lower dementia risk. Psychiatric News. 2004; 39(14):26.
Kulkarni J, et al. Estrogen in severe mental illness: a potential new treatment approach. Arch Gen Psychiatry. 2008; 65: 955-60.
Pae CU, Mandelli L, Han C, Ham BJ, Masand PS, Patkar AA, Steffens DC, De Ronchi D, Serretti A. Do estradiol levels influence on the cognitive function during antidepressant treatments in post-menopausal women with major depressive disorder? A comparison with pre-menopausal women. Neuro Endocrinol Lett. 2008 Aug;29(4):500-6.
Kulkarni J. Oestrogen – a new treatment approach for schizophrenia? Med J Aust. 2009 Feb 16;190(4 Suppl):S37-8.
Butler C, Zeman AZ. Neurological syndromes which can be mistaken for psychiatric conditions. J Neurol Neurosurg Psychiatry. 2005 Mar;76 Suppl 1:i31-38.
Comings DE. Role of genetic factors in human sexual behavior based on studies of Tourette Syndrome and ADHD probands and their relatives. Am J Med Genet. 1994 Sep 15; 54(3):227-41.
Sandyk R. Naltrexone suppresses abnormal sexual behavior in Tourette's syndrome. Int J Neurosci. 1988 Nov; 43(1-2):107-10.
Comings DE, Comings BG. A case of familial exhibitionism in Tourette's syndrome successfully treated with haloperidol. Am J Psychiatry. 1982 Jul; 139(7):913-5.
Glad S, Nyland H, Myhr KM. Benign multiple sclerosis. Acta Neurol Scand Suppl. 2006; 183:55-7.
Goldman Consensus Group. The Goldman Consensus statement on depression in multiple sclerosis. Mult Scler. 2005 Jun; 11(3):328-37.
Habek M, Brinar M, Brinar VV, Poser CM. Psychiatric manifestations of multiple sclerosis and acute disseminated encephalomyelitis. Clin Neurol Neurosurg. 2006 Mar; 108(3):290-4. Epub 2005 Dec 20.
Kułakowska A, Drozdowski W, Halicka D. [Emotional disorders in patients with multiple sclerosis] Przegl Lek. 2001; 58(9):873-6. [Article in Polish]
Mendez MF. The neuropsychiatry of multiple sclerosis. Int J Psychiatry Med. 1995; 25(2):123-30.
Perlmutter D. BrainRecovery.com: powerful therapy for challenging brain disorders. Naples, FL: The Perlmutter Health Center, 2000.
Treadwell-Deering D, Evankovich K, Lotze T. Case report: "Purely" psychiatric presentation of multiple sclerosis in an adolescent boy. J Am Acad Child Adolesc Psychiatry. 2007 Sep; 46(9):1213-7.
Zarei M, Chandran S, Compston A, Hodges J. Cognitive presentation of multiple sclerosis: evidence for a cortical variant. J Neurol Neurosurg Psychiatry. 2003 Jul; 74(7):872-7.
Schwerzmann M, Wiher S, Nedeltchev K, Mattle HP, Wahl A, Seiler C, Meier B, Windecker S. Percutaneous closure of patent foramen ovale reduces the frequency of migraine attacks. Neurology. 2004 Apr 27; 62(8):1399-401.
Gupta, V.K. 2004. Percutaneous closure of patent foramen ovale reduces the frequency of migraine attacks: To the editor. Neurology. 62(Nov. 9):1760-1761.
Adler CS, Morrissey-Adler S. Psychiatric aspects of headache. Panminerva Med. 1982 Apr-Jun; 24(2):167-72.
Holmes Jr., D.R. Strokes and holes and headaches: are they a package deal? Lancet. 2004 Nov 20; 364:1840-1842.
Homma S, Sacco RL, Di Tullio MR, Sciacca RR, Mohr JP; PFO in Cryptogenic Stroke Study (PICSS) Investigators. Effect of medical treatment in stroke patients with patent foramen ovale: patent foramen ovale in Cryptogenic Stroke Study. Circulation. 2002 Jun 4; 105(22):2625-31. http://www.circ.ahajournals.org/ cgi/content/abstract/ 105/22/262
Horton, SC. Bunch, TJ. 2004. Patent foramen ovale and stroke. Mayo Clinic Proceedings 79(January):79-88.
Morandi, EGP. Anzola and E. Onorato. Transcatheter closure of patent foramen ovale: A new migraine treatment? Journal of Interventional Cardiology 2003 16(February):39-42.
Post, MC. et al. Closure of a patent foramen ovale is associated with a decrease in prevalence of migraine. Neurology 2004 62(April 27):1439-1440.
Yee AJ. Effectiveness of high-dose riboflavin in migraine prophylaxis. Neurology 1999; 52:431–432.
Fann JR, Burington B, Leonetti A, Jaffe K, Katon WJ, Thompson RS. Psychiatric illness following traumatic brain injury in an adult health maintenance organization population. Arch Gen Psychiatry. 2004 Jan; 61 (1): 53-61.
MacKenzie JD, et al. Brain atrophy in mild or moderate traumatic brain injury: a longitudinal quantitative analysis. AJNR Am J Neuroradiol. 2002 Oct; 23(9):1509-15.
Kant R, Smith-Seemiller L, Duffy JD. Obsessive-compulsive disorder after closed head injury: review of literature and report of four cases. Brain Inj. 1996 Jan;10(1):55-63.
Gale SD, Baxter L, Roundy N, Johnson SC. Traumatic brain injury and grey matter concentration: a preliminary voxel based morphometry study. J Neurol Neurosurg Psychiatry. 2005 Jul; 76(7):984-8. Whiplash
Warren J. Maurice Ravel's Amusia. J R Soc Med. 2003 Aug; 96(8):424.
Otte A, Audenaert K, Otte K. Did Maurice Ravel have a whiplash syndrome? Med Sci Monit. 2003 May; 9(5):LE9.
Jeffrey, S. Gum disease seen as stroke risk factor. Neurology Update. 1999 May 11; 35(18).
Espárrago Llorca G, Castilla-Guerra L, Fernández Moreno MC, Ruiz Doblado S, Jiménez Hernández MD. Post-stroke depression: an update. Neurologia. 2015 Jan-Feb;30(1):23-31.
La Mancusa JC, Cole AR. Visual manifestations of occipital lobe infarction in three patients on a geriatric psychiatry unit. J Geriatr Psychiatry Neurol. 1988 Oct-Dec; 1(4):231-4.
Anderson SW, Rizzo M. Hallucinations following occipital lobe damage: the pathological activation of visual representations. J Clin Exp Neuropsychol. 1994 Oct; 16(5):651-63.
Mawe GM, Coates MD, Moses PL. Review article: intestinal serotonin signaling in irritable bowel syndrome. Aliment Pharmacol Ther. 2006 Apr 15; 23(8):1067-76. http://www.neurology.org /cgi/eletters/ 62/8/1399
De Santis G, Lattuada P, D'Arrigo G, Frediani F. An unusual case of paradoxical embolism in a young patient affected by stroke. Neurol Sci. 2015 Feb;36(2):335-7.
Neşe Tuncer, Nazire Afşar, Tülin Tanrıdağ, Önder Us. Pathological Laughing Following Pontine Infarction Due To Basilar Artery Stenosis. Marmara Medical Journal 2005;18(1);28-31.
Salam A, Sanmuganathan P, Pycock C. Unusual presentation of basilar artery stroke secondary to patent foramen ovale: a case report. J Med Case Reports. 2008 Mar 7;2:75.
Gittleman HR, Ostrom QT, Rouse CD, Dowling JA, de Blank PM et al. Trends in central nervous system tumor incidence relative to other common cancers in adults, adolescents, and children in the United States, 2000 to 2010. Cancer. 2015 Jan 1;121(1):102-12.
Kocher R, Linder M, Stula D. [Primary brain tumors in psychiatry] Schweiz Arch Neurol Neurochir Psychiatr. 1984; 135(2):217-27. [Article in German]
Ko SM, Kok LP. Cerebral tumours presenting with psychiatric symptoms. Singapore Med J. 1989 Jun; 30(3): 282-4.
Kundi M, Mild K, Hardell L, Mattsson MO. Mobile telephones and cancer--a review of epidemiological evidence. J Toxicol Environ Health B Crit Rev. 2004 Sep-Oct; 7(5):351-84.
Hansson Mild K, Hardell L, Kundi M, Mattsson MO. Mobile telephones and cancer: is there really no evidence of an association? (Review). Int J Mol Med. 2003 Jul; 12(1):67-72.
Deutsch SI, Rosse RB, Sud IM, Burket JA. Temporal lobe epilepsy confused with panic disorder: implications for treatment. Clin Neuropharmacol. 2009 May-Jun;32(3):160-2.
Ghadirian AM, Gauthier S, Bertrand S. Anxiety attacks in a patient with a right temporal lobe meningioma. J Clin Psychiatry. 1986 May; 47(5):270-1.
Kellner M, Hirschmann M, Wiedemann K. Panic attacks caused by temporal tumors: an exemplary new case and a review. Depress Anxiety. 1996-1997; 4(5):243-5.
Hoffer ZS, Allen SL, Mathews M. Treatment of psychiatric symptoms associated with a frontal lobe tumor through surgical resection. Am J Psychiatry. 2007 Jun; 164(6):877-82.
John G, Eapen V, Shaw GK. Frontal glioma presenting as anxiety and obsessions: a case report. Acta Neurol Scand. 1997 Sep; 96(3):194-5.
Bhatia MS. Cotard's Syndrome in parietal lobe tumor. Indian Pediatr. 1993 Aug;30(8):1019-21.
Lance JW, Cooper B, Misbach J. Visual hallucinations as a symptom of right parieto-occipital lesions. Proc Aust Assoc Neurol. 1974;11:209-17.
Lance JW. Simple formed hallucinations confined to the area of a specific visual field defect. Brain. 1976 Dec;99(4):719-34.
Nagaratnam N, Virk S, Brdarevic O. Musical hallucinations associated with recurrence of a right occipital meningioma. Br J Clin Pract. 1996 Jan-Feb;50(1):56-7.
Zindr V, Prasko J. [Paranoid hallucinatory syndrome in patients with metastatic carcinoma of the occipital lobe] Cesk Psychiatr. 1986 Feb;82(1):25-9.
Ghadirian AM, Gauthier S, Bertrand S. Anxiety attacks in a patient with a right temporal lobe meningioma. J Clin Psychiatry. 1986 May;47(5):270-1.
Kellner M, Hirschmann M, Wiedemann K. Panic attacks caused by temporal tumors: an exemplary new case and a review. Depress Anxiety. 1996-1997;4(5):243-5.
Malamud N. Psychiatric disorder with intracranial tumors of limbic system. Arch Neurol. 1967 Aug;17(2):113-23. [No abstract available]
Sandyk R. Psychotic behavior associated with cerebellar pathology. Int J Neurosci. 1993 Jul-Aug;71(1-4):1-7.
Khuan TC, Dass D, Majeed H. Psychiatric presentation of thalamic tumour: a case report. Med J Malaysia. 1979 Sep; 34(1):38-41.
Banas A. [Paranoid syndrome in a patient with intracranial tumor] Psychiatr Pol. 1990 Sep-Oct; 24(5):53-6. [Article in Polish]
Ferraro TN, Dlugos DJ, Buono RJ. Role of genetics in the diagnosis and treatment of epilepsy. Expert Rev Neurother. 2006 Dec;6(12):1789-800.
Blumer D. Evidence supporting the temporal lobe epilepsy personality syndrome. Neurology. 1999; 53(5 Suppl 2):S9-12.
Devinsky O, Lai G. Spirituality and religion in epilepsy. Epilepsy Behav. 2008 May;12(4):636-43. Epub 2008 Jan 2.
Devinsky, O. Morrell, M.J. and Vogt, B.A. Contributions of anterior cingulate cortex to behaviour. Brain 118:279-306, 1995.
Lopez KA, Seastrunk JW 2nd Temporal lobe epilepsy: a new entity in psychiatry. J Psychiatr Nurs Ment Health Serv. 1980 Aug; 18(8):10-5.
Schmitz EB, Moriarty J, Costa DC, Ring HA, Ell PJ, Trimble MR. Psychiatric profiles and patterns of cerebral blood flow in focal epilepsy: interactions between depression, obsessionality, and perfusion related to the laterality of the epilepsy. J Neurol Neurosurg Psychiatry. 1997 May; 62(5):458-63.
Stein MB, Millar TW, Larsen DK, Kryger MH. Irregular breathing during sleep in patients with panic disorder. Am J Psychiatry. 1995 Aug; 152(8):1168-73.
Trimble M, Freeman A. An investigation of religiosity and the Gastaut-Geschwind syndrome in patients with temporal lobe epilepsy. Epilepsy Behav. 2006 Nov; 9(3):407-14. Epub 2006 Aug 17.
Epilepsy.com [Accessed 2010]
Oldani A, Zucconi M, Castronovo C, Ferini-Strambi L. Nocturnal frontal lobe epilepsy misdiagnosed as sleep apnea syndrome. Acta Neurol Scand. 1998 Jul;98(1):67-71.
Alemayehu S, Bergey GK, Barry E, Krumholz A, Wolf A, Fleming CP, Frear EJ Jr. Panic attacks as ictal manifestations of parietal lobe seizures. Epilepsia. 1995 Aug; 36(8):824-30.
Barr, William. Is there an epileptic personality? NYU Comprehensive Epilepsy Center September 22, 2003.
Sveinbjornsdottir S, Duncan JS. Parietal and occipital lobe epilepsy: a review. Epilepsia. 1993 May-Jun;34(3):493-521.
Lanzino G, Cannizzaro D, Villa SL. Subtemporal approach for distal basilar occlusion for giant aneurysm. Nuances and advantages of the subtemporal approach. Neurosurg Focus. 2015 Jan;38.
Bien CG, Benninger FO, Urbach H, Schramm J, Kurthen M, Elger CE. Localizing value of epileptic visual auras. Brain. 2000 Feb;123 ( Pt 2):244-53.
Menon B. Symptomatic occipital epilepsy misdiagnosed as migraine. Headache. 2007 Feb;47(2):287-9.
Williamson PD, Thadani VM, Darcey TM, Spencer DD, Spencer SS, Mattson RH. Occipital lobe epilepsy: clinical characteristics, seizure spread patterns, and results of surgery. Ann Neurol. 1992 Jan;31(1):3-13.
Levin B, Duchowny M. Childhood obsessive-compulsive disorder and cingulate epilepsy. Biol Psychiatry. 1991 Nov 15;30(10):1049-55.
Panuccio G, Curia G, Colosimo A, Cruccu G, Avoli M. Epileptiform synchronization in the cingulate cortex. Epilepsia. 2009 Mar;50(3):521-36.
Schrader D, Langill L, Singhal A, Steinbok P, Connolly MB. Cingulate lesions presenting with epileptic spasms. J Clin Neurophysiol. 2009 Oct;26(5):342-7.
Stolle M, Sieben C, Püst B. [Panic attacks simulated by occipital lobe seizures] Z Kinder Jugendpsychiatr Psychother. 2009 May;37(3):203-7. [Article in German]
Plotnik AN, Carney P, Schweder P, O'Brien TJ, Velakoulis D, Drummond KJ. Seizures initially diagnosed as panic attacks: case series. Aust N Z J Psychiatry. 2009 Sep;43(9):878-82.Scalise A, Placidi F, Diomedi M, De Simone R, Gigli GL. Panic disorder or epilepsy? A case report. J Neurol Sci. 2006 Jul 15;246(1-2):173-5.
Stoffers JM, Lieb K. Pharmacotherapy for borderline personality disorder--current evidence and recent trends. Curr Psychiatry Rep. 2015 Jan;17(1):534.
Kepler, EJ. Moersch, FP. The psychiatric manifestations of hypoglycemia. Am J Psychiatry. 1937 July; 94:89-110.
Foster JW, Hart RG. Hypoglycemic hemiplegia: two cases and a clinical review. Stroke. 1987; 18:944-946.
Fernandez-Mayoralas DM, Munoz-Jareno N, Manzano-Palomo MS, Campos-Castello J. Acute hemiparesis in a boy with type 1 diabetes. Eur J Paediatr Neurol. 2004; 8(3):161-4.
Carter F, Taylor C. Transient hypoglycemic hemiparesis. J Natl Med Assoc. 2002 Nov; 94(11):999-1001.
Boylan-Starks L. Hypoglycemic hemiplegia: a case study. Heart Lung. 1995 Jul-Aug; 24(4):330-2.
Behrman S, Chouliaras L, Ebmeier KP. Considering the senses in the diagnosis and management of dementia. Maturitas. 2014 Apr;77(4):305-10.
Guarneros M, Ortiz-Romo N, Alcaraz-Zubeldia M, Drucker-Colín R, Hudson R. Nonoccupational environmental exposure to manganese is linked to deficits in peripheral and central olfactory function. Chem Senses. 2013 Nov;38(9):783-91.
Atanasova B, Graux J, El Hage W, Hommet C, Camus V, Belzung C. Olfaction: a potential cognitive marker of psychiatric disorders. Neurosci Biobehav Rev. 2008 Sep; 32(7):1315-25. Epub 2008 May 13.
Meats P. Olfactory hallucinations. Br Med J (Clin Res Ed). 1988 Feb 27; 296(6622):645.
Dileo JF, Brewer WJ, Hopwood M, Anderson V, Creamer M. Olfactory identification dysfunction, aggression and impulsivity in war veterans with post-traumatic stress disorder. Psychol Med. 2008 Apr; 38(4):523-31.
Vermetten E, Bremner JD. Olfaction as a traumatic reminder in posttraumatic stress disorder: case reports and review. J Clin Psychiatry. 2003 Feb; 64(2):202-7.
Karsz FR, et al. Olfactory impairments in child attention-deficit/hyperactivity disorder. J Clin Psychiatry. 2008 Sep; 69(9):1462-8.
Doty RL, Shaman P, Kimmelman CP, Dann MS. University of Pennsylvania Smell Identification Test: a rapid quantitative olfactory function test for the clinic. Laryngoscope. 1984 Feb; 94(2 Pt 1):176-8.
Doty RL, Shaman P, Dann M. Development of the University of Pennsylvania Smell Identification Test: a standardized microencapsulated test of olfactory function. Physiol Behav. 1984 Mar; 32(3):489-502.
Immig K, Gericke M, Menzel F, Merz F, Krueger M, Schiefenhövel F, Lösche A, Jäger K, Hanisch UK, Biber K, Bechmann I. CD11c-positive cells from brain, spleen, lung, and liver exhibit site-specific
immune phenotypes and plastically adapt to new environments. Glia. 2015 Apr;63(4):611-25.
Crone CC, Gabriel GM, DiMartini A. An overview of psychiatric issues in liver disease for the consultation-liaison psychiatrist. Psychosomatics. 2006 May-Jun; 47(3):188-205.
Haussinger D. [Hepatic encephalopathy] Schweiz Rundsch Med Prax. 2006 Oct 4; 95(40):1543-9. [Article in German]
Munoz SJ. Driving with minimal hepatic encephalopathy: real world consequences? Am J Gastroenterol. 2007; 102(9):1910-1.
Bajaj JS. Management options for minimal hepatic encephalopathy. Expert Rev Gastroenterol Hepatol. 2008 Dec; 2(6):785-90.
Bajaj JS, et al. Probiotic yogurt for the treatment of minimal hepatic encephalopathy. Am J Gastroenterol. 2008 Jul; 103(7): 1707-15.
Malaguarnera M, Greco F, Barone G, Gargante MP, Malaguarnera M, Toscano MA. Bifidobacterium longum with fructo-oligosaccharide (FOS) treatment in minimal hepatic encephalopathy: a randomized, double-blind, placebo-controlled study. Dig Dis Sci. 2007 Nov; 52(11):3259-65. Epub 2007 Mar 28.
Thannickal VJ(1), Murthy M, Balch WE, Chandel NS, Blue journal conference. Aging and susceptibility to lung disease. Am J Respir Crit Care Med. 2015 Feb 1;191(3):261-9.
Sakkijha H, Idrees MM. Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension: Pulmonary hypertension due to lung diseases and/or hypoxia. Ann Thorac Med. 2014 Jul;9(Suppl 1):S56-61.
Jain A, Lolak S. Psychiatric aspects of chronic lung disease. Curr Psychiatry Rep. 2009 Jun; 11(3):219-25.
Duffy J, Hansen JL. Psychiatric aspects of chronic lung disease. Minn Med. 1969 Sep; 52(9):1559-61.
Shanmugam G, Bhutani S, Khan DA, Brown ES. Psychiatric considerations in pulmonary disease. Psychiatr Clin North Am. 2007 Dec; 30(4):761-80.
De Santis G(1), Lattuada P, D'Arrigo G, Frediani F. An unusual case of paradoxical embolism in a young patient affected by stroke. . Neurol Sci. 2015 Feb;36(2):335-7.
Birket-Smith M, Rasmussen A. Screening for mental disorders in cardiology outpatients. Nord J Psychiatry. 2008;62(2):89.
Hildingh C, Baigi A. The association among hypertension and reduced psychological well-being, anxiety and sleep disturbances: a population study. Scand J Caring Sci. 2010 Jun;24(2):366-71.
Horstmann A, Frisch S, Jentzsch RT, Müller K, Villringer A, Schroeter ML. Resuscitating the heart but losing the brain: brain atrophy in the aftermath of cardiac arrest. Neurology. 2010 Jan 26;74(4):306-12.
Moulaert VR, Wachelder EM, Verbunt JA, Wade DT, van Heugten CM. Determinants of quality of life in survivors of cardiac arrest. J Rehabil Med. 2010 Jun;42(6):553-8.
Reich P, Regestein QR, Murawski BJ, DeSilva RA, Lown B. Unrecognized organic mental disorders in survivors of cardiac arrest. Am J Psychiatry. 1983 Sep; 140(9):1194-7.
Wu BY, Wu BJ, Lee SM, Sun HJ, et al.Prevalence and associated factors of comorbid skin diseases in patients with schizophrenia: a clinical survey and national health database study. Gen Hosp Psychiatry. 2014 Jul-Aug;36(4):415-21.
Mercan S, Kivanç Altunay I. [Psychodermatology: a collaboration between psychiatry and dermatology] Turk Psikiyatri Derg. 2006 Winter; 17(4):305-13. [Article in Turkish]
Cheour M, Zribi H, Abdelhak S, Drira S, Ben Osman A. [Darier's disease: an evaluation of its neuropsychiatric component] Encephale. 2009 Feb; 35(1):32-5. Epub 2008 Jun 2. [Article in French]
Dehen L, Taieb C, Myon E, Dubertret L. [Dermatosis and depressive symptoms] Ann Dermatol Venereol. 2006 Feb; 133(2):125-9. [Article in French]
Filaković P, Biljan D, Petek A. Depression in dermatology: an integrative perspective. Psychiatr Danub. 2008 Sep; 20(3):419-25.
Gupta MA, Gupta AK, Ellis CN, Koblenzer CS. Psychiatric evaluation of the dermatology patient. Dermatol Clin. 2005 Oct; 23(4):591-9.
Harth W, Hillert A, Hermes B, Seikowski K, Niemeier V, Freudenmann RW. [Suicidal behavior in dermatology] Hautarzt. 2008 Apr; 59(4):289-96.
Hellwig B, Hesslinger B, Walden J. Darier's Disease and psychosis. Psychiatry Res. 1996 Oct 16; 64(3): 205-7.
Hosoda S, Kohno M, Kumada H. [Psychiatric symptoms related to interferon treatment for chronic hepatitis] Seishin Shinkeigaku Zasshi. 2003; 105(6):768-86. [Article in Japanese]
Jafferany M. Lithium and psoriasis: what primary care and family physicians should know. Prim Care Companion J Clin Psychiatry. 2008; 10(6):435-9.
Mostaghimi L. Prevalence of mood and sleep problems in chronic skin diseases: a pilot study. Cutis. 2008 May; 81(5):398-402.
Myles PS, Buchanan FF, Bain CR. The effect of hair colour on anaesthetic requirements and recovery time after surgery. Anaesth Intensive Care. 2012 Jul;40(4):683-9.
Folope V, Coëffier M, Déchelotte P. [Nutritional deficiencies associated with bariatric surgery] Gastroenterol Clin Biol. 2007 Apr; 31(4):369-77.
Grimalt R. Psychological aspects of hair disease. J Cosmet Dermatol. 2005 Jun; 4(2):142-7.
Khalidi N, Wesley JR, Thoene JG, Whitehouse WM Jr, Baker WL. Biotin deficiency in a patient with short bowel syndrome during home parenteral nutrition. JPEN J Parenter Enteral Nutr. 1984 May-Jun; 8(3):311-4.
Levenson JL. Biotin-responsive depression during hyperalimentation. JPEN J Parenter Enteral Nutr. 1983 Mar-Apr; 7(2):181-3.
Manolache L, Benea V. Stress in patients with alopecia areata and vitiligo. J Eur Acad Dermatol Venereol. 2007 Aug; 21(7):921-8.
Olszewska M, Warszawik O, Rakowska A, Słowińska M, Rudnicka L. Methods of hair loss evaluation in patients with endocrine disorders. Endokrynol Pol. 2010 Jul-Aug;61(4):406-11.
Stough D, Stenn K, Haber R, Parsley WM, Vogel JE, Whiting DA, Washenik K. Psychological effect, pathophysiology, and management of androgenetic alopecia in men. Mayo Clin Proc. 2005 Oct; 80(10):1316-22.
Whittle N, Lubec G, Singewald N. Zinc deficiency induces enhanced depression-like behaviour and altered limbic activation reversed by antidepressant treatment in mice. Amino Acids. 2009 Jan; 36(1):147-58.
Ekici A, Ekici M, Oğuztürk O, Karaboğa I, Cimen D, Senturk E. Personality profiles in patients with obstructive sleep apnea. Sleep Breath. 2013 Mar;17(1):305-10.
Marcoux LA, Michon PE, Lemelin S, Voisin JA, Jackson PL. Feeling but not caring: empathic alteration in narcissistic men with high psychopathic traits. Psychiatry Res. 2014 Dec 30;224(3):341-8. doi: 10.1016/j.pscychresns.2014.10.002.
Booth BD, Fedoroff JP, Curry SD, Douglass AB. Sleep apnea as a possible factor contributing to aggression in sex offenders. J Forensic Sci. 2006 Sep; 51(5):1178-81.
Dennis JL, Crisham KP. Chronic assaultive behavior improved with sleep apnea treatment. J Clin Psychiatry. 2001 Jul; 62(7):571-2.
Ireland JL, Culpin V. The relationship between sleeping problems and aggression, anger, and impulsivity in a population of juvenile and young offenders. J Adolesc Health. 2006 Jun; 38(6):649-55.
Skjodt NM, Atkar R, Easton PA. Screening for hypothyroidism in sleep apnea. Am J Respir Crit Care Med. 1999 Aug; 160(2):732-5.
Lanza G, Cantone M, Lanuzza B, Pennisi M, Bella R, Pennisi G), Ferri R(2). Distinctive patterns of cortical excitability to transcranial magnetic stimulation in obstructive sleep apnea syndrome, restless legs syndrome, insomnia, and sleep deprivation. Sleep Med Rev. 2015 Feb;19:39-50.
Gupta R, Zalai D, Spence DW, BaHammam AS, Ramasubramanian C, Monti JM, Pandi-Perumal SR. When insomnia is not just insomnia: the deeper correlates of disturbed sleep with reference to DSM-5.Asian J Psychiatr. 2014 Dec;12:23-30.
Saletu M, Anderer P, Saletu B, Lindeck-Pozza L, Hauer C, Saletu-Zyhlarz G. EEG mapping in patients with restless legs syndrome as compared with normal controls. Psychiatry Res. 2002 Aug 20; 115(1-2):49-61.
Crabtree VM, Ivanenko A, O'Brien LM, Gozal D. Periodic limb movement disorder of sleep in children. J Sleep Res. 2003 Mar; 12(1):73-81.
Frohnhofen H, Fulda S, Frohnhofen K, Popp R. Validation of the Essener Questionnaire of Age and Sleepiness in the elderly using pupillometry. Adv Exp Med Biol. 2013;755:125-32.
Serkh K, Forger DB. Optimal schedules of light exposure for rapidly correcting circadian misalignment. PLoS Comput Biol. 2014 Apr 10;10(4):e1003523.
Ostenfeld I. Abstinence from night sleep as a treatment for endogenous depressions: the earliest observations in a Danish mental hospital (1954) and an analysis of the causal mechanism. Dan Med Bull. 1986 Feb; 33(1):45-9.
Vandeputte M, de Weerd A. Sleep disorders and depressive feelings: a global survey with the Beck depression scale. Sleep Med. 2003 Jul; 4(4):343-5.
Yin, L. Wang,J. Klein, PS. Lazar, MA. Nuclear receptor rev-erb is a critical lithium-sensitive component of the circadian clock. Science 311 (5763): 1002-1005.
Nomura T, Inoue Y, Kobayashi M, Namba K, Nakashima K. Characteristics of obstructive sleep apnea in patients with Parkinson's disease. J Neurol Sci. 2013 Apr 15;327(1-2):22-4.
Lee W, Lee SA, Chung YS, Kim WS. The relation between apnea and depressive symptoms in men with severe obstructive sleep apnea: mediational effects of sleep quality. Lung. 2015 Apr;193(2):261-7.
Takeuchi S, Kitamura T, Ohbuchi T, Koizumi H, et al. Relationship between sleep apnea and thyroid function. Sleep Breath. 2015 Mar;19(1):85-9.Ozcan KM, Selcuk A, Ozcan I, Ozdas T, Ozdogan F, Acar M, Dere H. Incidence of hypothyroidism and its correlation with polysomnography findings in obstructive sleep apnea. Eur Arch Otorhinolaryngol. 2014 Nov;271(11):2937-41.
O'Brien LM, et al. Sleep and neurobehavioral characteristics of 5-to-7-year-old children with parentally reported symptoms of attention-deficit/hyperactivity disorder. Pediatrics. 2003 Mar; 111(3):554-63.
Oldani A, Zucconi M, Castronovo C, Ferini-Strambi L. Nocturnal frontal lobe epilepsy misdiagnosed as sleep apnea syndrome. Acta Neurol Scand. 1998 Jul; 98(1):67-71.
Booth BD, MD, Fedoroff JP, MD, Curry SD, BA (Hon), Douglass AB, MD. Sleep apnea as a possible factor contributing to aggression in sex offenders. Journal of Forensic Sciences. 2006; 51(5):1178–1181.
Gottlieb DJ, et al. Symptoms of sleep-disordered breathing in 5-year-old children are associated with sleepiness and problem behaviors. Pediatrics. 2003 Oct; 112(4):870-7.
Goncalves MA, Paiva T, Ramos E, Guilleminault C. Obstructive sleep apnea syndrome, sleepiness, and quality of life. Chest. 2004 Jun; 125(6):2091-6.
Yantis MA. Identifying depression as a symptom of sleep apnea. J Psychosoc Nurs Ment Health Serv. 1999 Oct; 37(10):28-34.
Ohayon MM. The effects of breathing-related sleep disorders on mood disturbances in the general population. J Clin Psychiatry. 2003 Oct; 64(10):1195-200.
Skjodt NM, Atkar R, Easton PA. Screening for hypothyroidism in sleep apnea. Am J Respir Crit Care Med. 1999 Aug; 160(2):732-5.
Abramowitz, Jonathan S. & Arthur C. Houts (Eds) Concepts and Controversies in Obsessive-Compulsive Disorder Springer 2005.
Ashby-Sharpe, Virginia & Alan I. Faden Medical Harm: Historical, Conceptual and Ethical Dimensions of Iatrogenic Illness Cambridge University Press 1998.
Ashford, Nicholas Askounes & Claudia S. Miller Chemical Exposures: Low Levels and High Stakes John Wiley & Sons 1998.
Austin, Steve, Forrest Batz, Alan R. Gaby, Donald J. Brown, Eric Yarnell, George Constantine, The A-Z Guide to Drug-Herb-Vitamin Interactions: How to Improve Your Health and Avoid Problems When Using Common Medications and Natural Supplements Together Three Rivers Press 1999.
Bailey, Donald B. (Ed) Critical Thinking about Critical Periods Brookes Publishing Company 2001.
Barbour Alan G. Lyme Disease: The Cause, the Cure, the Controversy Johns Hopkins University Press 1996.
Baron-Cohen, Simon Mindblindness: An Essay on Autism and Theory of Mind The MIT Press 1997.
Baron-Cohen, Simon, Svetlana Lutchmaya, Rebecca Knickmeyer Prenatal Testosterone in Mind: Amniotic Fluid Studies New Edition The MIT Press; 2006.
Barrett, Stephen J. & Ronald E. Gots Chemical Sensitivity: The Truth about Environmental Illness Prometheus Books 1998.
Bergemann, Niels (Ed), Riecher-Rössler, A. (Ed) Estrogen Effects in Psychiatric Disorders Springer2005.
Blaylock, Russell L. Excitotoxins: The Taste That Kills Health Press (NM) 1996.
Blum, Kenneth & Ernest P. Noble Handbook of Psychiatric Genetics CRC-Press 1996.
Blumer, Deitrich Psychiatric Aspects of Epilepsy Cambridge University Press 1987.
Braly, James & Patrick Holford Hidden Food Allergies: Is What You Eat Making You Ill? Basic Health Publications 2006.
Brizendine, Louann The Female Brain Morgan Road Books 2006.
Brostoff, Jonathan & Linda Gamlin Food Allergies and Food Intolerance: The Complete Guide to Their Identification and Treatment Healing Arts Press 2000.
Brostoff, Jonathan & Stephen J. Challacombe Food Allergy and Intolerance Saunders Ltd 2002.
Brown, James S. Environmental and Chemical Toxins and Psychiatric Illness American Psychiatric Publishing 2002.
Brown TM, Stoudemire A. Psychiatric Side Effects of Prescription and Over-the-Counter Medications: Recognition and Management American Psychiatric Press, Washington, DC,1998.
Brownlee, Shannon Overtreated: Why Too Much Medicine Is Making Us Sicker and Poorer Bloomsbury USA. 2007.
Burstall, Dawn. T. Michael Vallis, Geoffrey K. Turnbull I.B.S Relief: A Doctor, a Dietitian, and a Psychologist Provide a Team Approach to Managing Irritable Bowel Syndrome Wiley 1998.
Carbone Kathryn M. (Ed) Borna Disease Virus: Role in Neurobehavioral Disease ASM Press 2002.
Carter, James P. Racketeering in Medicine Hampton Roads Publishing Company 1992.
Cohen, Jay S. Over Dose: The Case Against the Drug Companies: Prescription Drugs, Side Effects, and Your Health Tarcher 2001.
Colborn, Theo, John Peterson Myers, Dianne Dumanoski Our Stolen Future: Are We Threatening Our Own Fertility, Intelligence, and Survival?-A Scientific Detective Story Dutton Books 1996.
Cone, William P. Kevin D. Randle, Russ Estes, The Abduction Enigma: The Truth Behind the Mass Alien Abductions of the Late Twentieth Century Tor Books 2000.
Coren, Stanley The Left-Hander Syndrome: The Causes and Consequences of Left-Handedness Vintage Books 1993.
Dowling, John The Great Brain Debate: Nature or Nurture? Joseph Henry Press 2004.
Durrant-Peatfield, Barry Your Thyroid and How to Keep It Healthy Hammersmith Press Limited 2006.
Edelman, Eva Natural Healing for Schizophrenia: And Other Common Mental Disorders Borage Books 2001.
First Michael B. & Allan Tasman Clinical Guide to the Diagnosis and Treatment of Mental Disorders
Fatemi S Hossein Neuropsychiatric Disorders and Infection Taylor & Francis 2007.
Freeman, Arthur Pain Management Psychotherapy: A Practical Guide Wiley 1998.
Fried, Stephen Bitter Pills: Inside the Hazardous World of Legal Drugs Bantam 1999.
Garcia Coll, Cinthia (Ed), & Elaine L. Bearer (Ed) Nature and Nurture: The Complex Interplay of Genetic and Environmental Influences on Human Behavior and Development . LEA, Inc. 2003.
Gatchel, Robert J. & Oordt, Marks S. Clinical Health Psychology and Primary Care: Practical Advice and Clinical Guidance for Successful Collaboration APA Books 2003.
Gilbere, Gloria. I Was Poisoned By My Body: The Odyssey of a Doctor Who Reversed Fibromyalgia, Leaky Gut Syndrome, and Multiple Chemical Sensitivity - Naturally! Lucky Press 2000.
Gilovich, Thomas How We Know What Isn't So Free Press 1993.
Goldberg, Burton & Larry Trivieri Chronic Fatigue, Fibromyalgia, and Lyme Disease Celestial Arts; 2nd edition 2004.
Goldstein, Joseph L. Snoring Can Kill!!: Discover How Sleep Apnea Can Be Ruining Your Life Caren Publishing Group 1999.
Graveline Duane Lipitor: Thief of Memory, Statin Drugs and the Misguided War on Cholesterol Infinity Publishing 2004.
Hamer, Dean & Peter Copeland Living with Our Genes Anchor Books, New York, NY. 1998.
Hobson, J. Allan & Jonathan A. Leonard Out of Its Mind: Psychiatry in Crisis: A Call for Reform Perseus Publishing 2002.
Holland, Jimmie C. et al (Eds.) Psycho-Oncology Oxford University Press 1998.
Holmes, Diana Tears Behind Closed Doors Normandi Publishing Limited 2002.
Hommes, O.R., M. Clanet H. Wekerle Genes and Viruses in Multiple Sclerosis Elsevier 2001.
Hui, Y.H. Foodborne Disease Handbook, Volume 4: Seafood and Environmental Toxins Dekker/CRC Press 2001.
Jones E. Anthony, (Ed), Alfred J. Meijer (Ed), Robert A.F.M. Chamuleau (Ed), Encephalopathy and Nitrogen Metabolism in Liver Failure Springer 2003.
Kaput, Jim & Raymond L. Rodriguez Nutritional Genomics: Discovering the Path to Personalized Nutrition Wiley-Interscience 2006.
Kummerer, Klaus Pharmaceuticals in the Environment Springer-Verlag New York, LLC. October 2004.
Lang, Denise & Kenneth Liegner Coping with Lyme Disease: A Practical Guide to Dealing with Diagnosis and Treatment Holt Paperbacks; Third Edition, 2004.
Lathe, Richard Autism, Brain and Environment Jessica Kingsley Publishers 2006.
Levy, S.B. The Antibiotic Paradox: How misuse of antibiotics destroys their curative powers. Perseus Books, Boston 2002.
Lewis, Kathleen Celebrate Life: New Attitudes for Living with Chronic Illness Arthritis Foundation 1999.
Marcus, Gary F. The Birth Of The Mind: How A Tiny Number of Genes Creates the Complexities of Human Thought Basic Books 2004.
McBride, Dabbs, James Heroes, Rogues, & Lovers: Testosterone and Behavior McGraw-Hill 2001.
McGuffin, Peter (Ed), Michael J. Owen (Ed), Irving I Gottesman (Ed) Psychiatric Genetics and Genomics Oxford University Press 2004.
Moore, David & James Jefferson Handbook of Medical Psychiatry Mosby 2004.
Moorey, Stirling & Steven Greer Cognitive Behaviour Therapy for People with Cancer Oxford University Press 2004.
Morgan, Brian & Roberta Morgan Brainfood Perigee Trade 1989.
Moyer, David Too Good to be True? Nutrients Quiet the Unquiet Brain--A Four Generation Bipolar Odyssey Nu-Tune Press 2004.
Nehlig, Astrid (Ed) Coffee, Tea, Chocolate, and the Brain CRC Press 2004.
Pacholok, Sally M., Stuart, Jeffrey J. Could It Be B12?: An Epidemic of Misdiagnoses Quill Driver Books, 2005.
Polevoy, T., Ron Reinhold, Marvin Ross Pig Pills Inc.: The Anatomy of an Academic and Alternative Health Fraud HealthWatcher.net Web: http://www.pigpills.com/Ramachandran, V. S., Sandra Blakeslee & Oliver Sacks Phantoms in the Brain: Probing the Mysteries of the Human Mind Harper Perennial 1999.
Ridley, Matt Nature via Nurture Harper Perennial 2004.
Rogers Sherry A. The E.I. Syndrome: An Rx for Environmental Illness Prestige Publications 1995.
Rosenthal, Sara M. The Thyroid Sourcebook McGraw Hill 1995.
Seelig, Mildred The Magnesium Factor Avery 2003. A 'must read' for panic attack and migraine sufferers
Segal, Sheldon J. & Luigi Mastroianni Hormone Use in Menopause and Male Andropause: A Choice for Women and Men Oxford University Press 2003.
Shafii, Mohammad Biological Rhythms, Mood Disorders, Light Therapy, and the Pineal Gland American Psychiatric Publishing 1990.
Shomon Mary J. Living Well with Hypothyroidism: What Your Doctor Doesn't Tell You... That You Need to Know Collins 2005.
Spiegel, David & Catherine Classen Group Therapy for Cancer Patients: A Research-based Handbook of Psychosocial Care Basic Books 2000.
Spiro Wagner, Pamela & Carolyn S., Spiro MD. Divided Minds: Twin Sisters and Their Journey Through Schizophrenia St. Martin's Press 2005.
Starr, Mark. Hypothyroidism Type 2: The Epidemic New Voice Publications 2005.
Surwit, Richard S. The Mind-Body Diabetes Revolution: The Proven Way to Control Your Blood Sugar by Managing Stress, Depression, Anger and Other Emotions Marlowe & Company 2005.
Vliet, Elizabeth Lee The Savvy Woman's Guide to Testosterone: How to Revitalize Your Sexuality, Strength and Stamina Chelsea Green Publishing Company 2005.
Walker, Sydney A Dose of Sanity Wiley October 16, 1997.
Williams, Roger The Prevention of Alcoholism Through Nutrition Bantam Books, 1981.
Wilson, James L. & Jonathan V. Wright Adrenal Fatigue: The 21st-Century Stress Syndrome Smart Publications 2002.
All about Depression http://www.allaboutdepression.com/
American Brain Tumor Association http://hope.abta.org/site/PageServer
American College of Neuropsychopharmacology http://www.acnp.org
American Council for Headache Education http://www.achenet.org
American Psychosomatic Society http://www.psychosomatic.org/
Behavioral Toxicology Society http://www.behavioraltoxicology.org/
Body Burden http://www.bodyburden.org
Crohn's and Colitis Foundation of America Inc. http://www.ccfa.org
Citizens for Safe Carpet P.O. Box 53344 , Cincinnati, OH 45253-0344, (513) 385-1111
Clinical Health Psychology http://www.health-psych.org/
Epigenetics Society epigeneticssocietyint.com/
Epigenome Network of Excellence http://www.epigenome-noe.net
Gender spectrum http://www.genderspectrum.org/
General Hospital Psychiatry http://www.sciencedirect.com
Human Epigenome Project http://www.epigenome.org
International Society of Psychoneuroendocrinology http://www.ispne.org/
Journal Epigenetics http://www.landesbioscience.com
Journal of Health Psychology http://hpq.sagepub.com/
Lupus Foundation http://www.lupus.org/
Multiple Sclerosis Association of America http://www.mymsaa.org/
National Center for Complementary and Alternative Medicine https://nccih.nih.gov/
National Institute for Occupational Safety and Health http://www.cdc.gov/niosh/
National Library of Medicine www.pubmed.gov
Neuroimmunological biology http://home.cc.umanitoba.ca
Nutritional and Metabolic TeleMedicine http://www.johndommissemd.com/
Parathyroid information http://www.parathyroid.com/
Pituitary Network Association http://www.pituitary.org
Psychoneuroimmunology Research Society http://www.pnirs.org/
Society of Behavioral Medicine http://www.sbm.org/
Townsend Letter http://www.townsendletter.com/
Wilson’s Disease Association http://www.wilsonsdisease.org/
Worldwide Society of Wolfram Syndrome Families http://www.wolframsyndrome.org/
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