At only 10 years old, Steve’s big brown eyes seemed to bulge from their sockets and his head and bony hands twitched relentlessly, as if he were in pain. He proceeded to pick up every piece of paper, no matter how filthy, with hands that were red and raw. Steve had spent most of the night violently scrubbing his hands in the bathroom and his mother took him to the hospital in the morning. \”Mommy, Mommy, let\’s leave!\” he cried. \”They\’re going to kill us. They\’re coming!\”
His mother tried her best to calm him, but she was beginning to panic. Two days before, Steve had been a perfectly normal little boy whose most serious health problems were the occasional cold or sore throat. He had become mentally ill overnight. Astonishingly, it was probably the minor sore throat, his doctors concluded (27). Today, researchers are starting to recognize that the bacteria and viruses that frequently invade our bodies and cause sore throats and other minor ailments may also unleash a host of major mental and emotional illnesses, including anorexia, schizophrenia and obsessive-compulsive disorder (24).
This theory sharply contrasts original thinking. Mental illnesses have been around since ancient times and people with psychiatric illnesses were often stigmatized. Greeks explained mental illness by an imbalance of bodily humours or fluids (12). During the middle ages, patients with mental illnesses were thought to have been possessed with demonic spirits and responsible for their ailment. Until recently, physicians believed psychiatric illness is chronic and psychiatry has very little to offer patients (18). Families often unrealistically felt blamed and responsible for having brought on the illness (12). Freudian beliefs have long held that mental and emotional trouble is primarily the result of poor parenting, especially by mothers. Indeed, until about 30 years ago, psychoanalysts frequently placed the blame for schizophrenia on \”schizophrenogenic\” mothers (18). Obsessive-compulsive disorder was also attributed to bad parenting. These theories added huge amounts of guilt to parents of mental ill but most experts now agree that there is little evidence to back it up. Virus is thought to be partly responsible for anxiety and panic disorders, schizophrenia, manic depression and antisocial personality disorder, which is characterized by impulsive, excessively emotional and erratic patterns of interpersonal behavior (15). Genetics doesn\’t appear to fully account for the occurrence of major psychiatric ailments.
If heredity alone were to blame, identical twins would develop schizophrenia with a high degree of concordance, but only 40% of cases in which one identical twin has the disease does the other twin have it as well (21). Though Autism has been observed to run in families, it strikes five of every 10,000 children apparently randomly (14). Depression and other affective disorders cannot be completely explained by damaged DNA either (16). Consider the case of syphilis, which is caused by the bacterium Treponema pallidum. In its final, or tertiary, stage, the disease can precipitate psychiatric problems like dementia, mania, depression, delusions and Tourette\’s like tics (5). In the interim, patients with syphilis who later developed psychiatric problems were often institutionalized as crazy. In the 1940s some scientists were beginning to make the connection with bacteria and virus as the cause but even with the link established, Freudian theories were in ascendance and few scientists were willing to consider that microbes might be a common source of other mental illness (8).
The hypothesis that mental illnesses are caused by infectious agents was first formulated in the 19th century. In 1845, the French neurologist Jean Esquirol noted that there were years when insanity seemed suddenly to extend to a great number of individuals (8). When bacteria became known, in 1874, spirochetes were identified as the cause of neurosyphilis (25) and by 1911, Emil Kraepelin was suggesting that infection during the years of early development lead to schizophrenia. After the influenza pandemic of 1918 and 1919, some individuals developed mania or schizophrenia following infection. This was more reason for speculation about viruses causing mental illnesses. After that observation, the hypothesis was mostly put to rest for about 50 years. Since the 1970s, interest in the infectious hypothesis of serious mental illnesses has been revived and stimulated by new experiments and technology (25).
Clinical Aspects of Mental Illness
The cause of mental conditions such as schizophrenia, bipolar disorder, autism, and obsessive-compulsive disorder are now thought to be virus-related (24). Scientists have noted that, in patients with autism, there is a certain point in post-natal development where brains are larger, testosterone may be somehow linked, and the amygdala may be enlarged in some brains (14). Schizophrenia symptoms and changes to the brain have also been clearly established and well documented. Mental illnesses like schizophrenia and bipolar disorder tend to stabilize with age where as dementias worsen as time goes on (24). Structural changes include enlargement of cerebral ventricles and loss of volume of temporal lobe structures. Functional changes include loss of cerebral blood flow, alterations of electrical activity, neuropsychological dysfunction, and neurological dysfunction (25). Viruses should be considered possible agents in all chronic central nervous system diseases of unknown etiology because of their tendency to attack or affect the nervous system preferentially (17). It is also known that occasional cases, later proven to be viral encephalitis or inflammation of the brain, may present with symptoms of schizophrenia or bipolar disorder (25). Drugs that have been shown to help with mental illnesses have antiviral properties as well (10).
Risk Factors Associated with Mental Illness
Torrey has identified 12 risk factors associated with schizophrenia and bipolar disorder. The risk factors include: genetics (if the person has close relatives with the disease, than the risk of developing schizophrenia is stronger), age of onset (the mean age is somewhere in the early 20s), gender (males are normally affected earlier in life and have more severe cases), season of birth (those born in winter and early spring months are 8% more likely to develop schizophrenia), regional differences (schizophrenia is very rare in tropical areas), urban birth (individuals born or raised in cities have increased risk for developing the disease), household crowding (the more people in a household, the more likely to develop schizophrenia), lower socioeconomic status (the rate of schizophrenia is highest in the lower class), prenatal and birth complications (individuals with schizophrenia had significantly more prenatal and birth complications), prenatal exposure to influenza (women with influenza in the mid-trimester of their pregnancies gave birth to offspring who had a higher rate of schizophrenia), having older siblings (researchers suggested explanation for this phenomenon was that older children are a source of viral infection, which may be transmitted to their mothers causing schizophrenia in the child), and famine during pregnancy (there is an increase in schizophrenia among offspring whose mother lived in famine conditions during pregnancy)(25,20).
Genetics, season of birth, and having older siblings are risk factors that seem to correlate with the infectious agent hypothesis for causing mental illness. Although it is commonly thought that genetics pre-determine schizophrenia and other mental illnesses, the genetic component of schizophrenia is a predisposition rather than a sufficient determinant of disease (25). Possible mechanisms relating genetics and infection include genetic determinants of receptors, immune responsiveness, and underlying tissue pathology (17). The so-called “birth-month” effect is very prevalent in many cases of mental illness including schizophrenia, bipolar disorder, and MS. Experiments in animals have shown that viruses are more likely to infect the central nervous system in conditions of cold (20). In 1993, a study assessed the risk of schizophrenia and age difference with older siblings and found evidence for a maternal viral infection. This suggested that a virus carried by older siblings and spread to the mother during pregnancy may cause schizophrenia (25).
Immune System Dysfunction
An individual might have been exposed to certain risk factors during pregnancy or shortly after birth, but there have also been reports of dysfunction of the immune system in individuals with serious mental illnesses. Most reports focus on immune hyporeactivity, having or showing abnormally low sensitivity to stimuli, as demonstrated by a diminished response to outside antigens such as guinea pig serum and pertussis (whooping cough) vaccine (23). The importance of such studies is that they suggested immune system dysfunction in seriously mentally ill patients prior to the use of antipsychotic medications, which, because they may also affect the immune system, have made such research more difficult (10). Studies of specific aspects of immune system dysfunction in individuals with serious mental illnesses have included lymphocyte (white blood cell) abnormalities, protein abnormalities, autoantibodies, and cytokines (substances secreted by the immune system that have effect on other cells) (11).
Direct Evidence of Viral Infection
Direct testing of a viral hypothesis of serious mental illnesses began in the 1950s. Scientists in the USSR claimed to have microscopically seen virus-like corpuscles in the cerebrospinal fluid and nasal secretions of many patients with schizophrenia (26). In Italy, researchers inoculated cerebrospinal fluid from patients with schizophrenia into chicken embryos and also claimed to have microscopically visualized virus-like particles (26). Since that time, the only researchers who have claimed to find virus particles in patients with serious mental illnesses have been Castillo and his colleagues in Havana, Cuba. They have described intracytoplasmic encapsulated structures similar to herpes viruses in freshly obtained postmortem brain tissue from patients with schizophrenia (6) and also in brain tissue from aborted fetuses from mothers with schizophrenia (6). Other direct evidence of viral infection in individuals with serious mental illnesses has included studies of viral antibodies, viral antigens, viral genomes, cytopathic effect (CPE) of specimens on cell cultures, and animal transmission experiments (25).
There have been more than 30 studies of viral antibodies in blood from individuals with serious mental illnesses and more than 15 studies of viral antibodies in the cerebrospinal fluid. The majority of these studies have focused on herpes viruses, cytomegalovirus, and Epstein-Barr virus (24). These studies have shown varied results. Two studies have reported increased serum antibody titers (concentration of antibody) to borna disease (an infectious neurological disease affecting horses and other mammal and bird species) virus in individuals with depression and bipolar disorder (2,3). There have also been suggestions of abnormal cerebrospinal fluid antibody titers to measles (22) and mumps (9) viruses. One study showed that 33% of mentally ill patients had a fourfold or greater change in serum antibody levels and 13% had a twofold or greater change in cerebrospinal fluid antibody level to a wide variety of viruses (1).
Microbes are very hard to grow in the lab since they are only active inside other living creatures but scientists\’ ability to do so has increased steadily over the last few decades. Other tools have allowed researchers to see their target more clearly (25). For about a decade, microbiologists have used a technique called polymerase chain reaction, or PCR, to replicate a small piece of genetic material over and over until it forms a quantity large enough to study and large enough to show the lingering traces of an infection (7). A new variant of PCR, called representational difference analysis, introduced in 1994, allows scientists to go one step further and compare the differences between two separate pieces of DNA (including healthy and diseased segments, for instance). The refinement of electron microscopes has permitted researchers to follow the \”footprints\” left by infection in patients\’ cerebrospinal fluid.
The introduction of CAT scans in the early 1970s has been another leap forward. Before then, only an X-ray or an autopsy could reveal damage to the brain, and then only in its grossest form. CAT scans show subtle changes that can be tracked over time, giving researchers a more accurate sense of a microbe\’s impact. MRI, developed in the early 1980s, has added three-dimensionality to pictures of the brain, and PET scans, invented soon after, have added motion. Now bacteria and viruses can be caught red-handed. Still, teasing out the tie between microbes and psychological problems has proved a difficult task, in no small part because of the cunning and guile of the pathogens themselves, which have many ways of attacking our bodies and brains (7).
Viruses Cause Mental Illness
T. pallidum, the bacteria that causes syphilis, proceeds in straightforward fashion: it attacks and kills brain cells. After entering the body, usually through sexual intercourse or through the mother\’s placenta into her fetus, the bacterium travels along the lymph system until it arrives at the brain (13). Once it lodges there, it spares few structures, inflaming some neurons and stripping the myelin, or insulation, from others. Without myelin, nerve impulses are slowed or stopped altogether (5). Other microbes are more devious.
The human immunodeficiency virus, which can cause anxiety, delirium, psychosis and suicidal impulses, uses a different strategy. Instead of directly attacking brain cells, it infects macrophages, the immune system enforcers that roam the bloodstream, engulfing foreign cells that may pose a threat to the body (5). The virus Chlamydia pneumoniae may use a similar trick, slipping into the brain and manufacturing cytokines, to cause Alzheimer\’s disease (26).
Streptococcal bacteria, like those that cause strep throat, take yet a different route. As they invade the body, they automatically trip the body\’s defense alarm, calling up the immune system\’s antibody soldiers. Once the skirmish begins, the bacteria camouflage themselves within that very immune system. They disguise themselves through molecular mimicry, cloaking themselves in proteins that imitate the body\’s own proteins, and thereby elude attack (5). For reasons scientists don\’t yet understand, the antibodies of some people, perhaps those with a genetic predisposition, then turn on their bodies\’ own tissues, assailing neurons in the basal ganglia. These structures, located between the more primitive lower brain and the higher cortical centers, help interpret information from the senses and are key to healthy emotions and behavior. The self-destruction instigated by streptococcal bacteria can be particularly dangerous to young children. This is because their immune systems are underdeveloped (1). Some believe that such self-induced damage leads some children to develop obsessive-compulsive disorder. In an experiment conducted earlier this year, researchers replaced the blood plasma of 28 children who suffered from OCD (and who had elevated levels of streptococcus antibodies) with healthy donor plasma, reasoning that such a switch would remove the trouble-making antibodies. Within a month, the incidence of tics declined by half, and their other OCD symptoms were reduced by 60% (4).
OCD isn\’t the only mental illness associated with streptococcus. Though anorexia nervosa has been tied to a distorted body image, societal pressure to be thin, discomfort with developing sexuality, and other emotional and cultural factors, doctors have also noted that the eating disorder sometimes appears or worsens after a case of strep throat (25). Streptococcus has been implicated as well in Tourette\’s syndrome and in Sydenham\’s chorea, which makes the arms and legs of those afflicted jerk in a manner often likened to dancing (1).
Those with mental illnesses have long been wrongly accused for bringing on their condition (12). Some believed that they had contact with demonic spirits or that it was punishment for their sins against God (18). Currently, a new hypothesis is one the rise: infectious agents (viruses) cause mental disease (24). A wide array of evidence supports this idea. Scientists have long known that diseases can cause mental problems. Consider one of the most infamous diseases of all: syphilis. This historic and lethal disease caused the death of Charles VIII of France, Adolf Hitler, Benito Mussolini and many more. It travels along the lymph system until it arrives at the brain. From there it strips myelin and inflames neuron causing the person to be apathetic, seize and have dementia (5). When penicillin was first used to treat syphilis, thousand of cured schizophrenics were released from mental asylums (27).
Children born in winter or early spring are more likely to develop mental disease (20). How could this be? Why would this be? The answers lie in viruses. Clinical and epidemiological aspects of mental disorder are consistent with a possible infectious etiology; however, there are no studies that provide a definite link between an infectious agent and these diseases (24). Mental illnesses such as schizophrenia, bipolar disorder, and neurosyhphilis have features that make infectious and autoimmune hypotheses attractive. More epidemiologic studies should be pursued to try to identify definitive infectious agents and possible modes of transmission (26).
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