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This is the second of an occasionally-appearing series on topics having to do with psychiatry.  Ever since Freud first wrote about young women sickened by their repressed sexual thoughts, America has been fascinated by the world of psychiatry.  And given that salacious introduction to the world of mental illness, who wouldn't be fascinated?  I too have been fascinated by the field of psychiatry, and I hope this series of articles will explain some of that fascination to readers in ways that are both enjoyable and enlightening.  For interested readers, the first installment of this series can be found here: http://www.dailykos.com/...

Schizophrenia is the Big Kahuna of psychiatric illness.  While not the most common of the psychiatric illnesses, schizophrenia is perhaps the disease that mostly captures the public imagination.  Literature and history are full of references to the bizarre behaviors and ramblings of mad kings and poets, prophets and criminals.  Today, we recognized many of these behaviors as the manifestations of schizophrenia.  The disease has been with us for a long time, has fascinated us for a long time, and today, despite our advances in medical science, schizophrenia still remains a burden and a mystery.

Science has been unable to identify a definitive cause of schizophrenia.  The current thinking among psychiatrists is that schizophrenia is a disorder of brain chemistry, and perhaps genetics plays a role in determining vulnerability to the disease.  But the detailed mechanisms for how chemistry or genetics actually causes schizophrenia remain hidden.  And the medications we give to people suffering from schizophrenia, medications used because of the idea that schizophrenia is caused by a disorder of brain chemistry, do not actually cure or resolve the illness, and can provide only partial symptomatic relief.  Schizophrenia remains a stubbornly chronic and mysterious illness.  However, there is now an accumulation of scientific evidence that suggests an infection might be the cause of schizophrenia.  An infectious cause of schizophrenia would mean not only a radical change in how we treat the illness, but how we think about psychiatric disease.

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Bizarre and odd are the hallmarks of schizophrenia.  The disease is characterized by disordered and delusional thinking, seeing, hearing, and feeling things that aren't there, a strange blank quality to the individual's emotional response, and odd behaviors and social interactions.  Indeed, talking with a schizophrenic can be an exercise in strangeness: the topics of conversation can include the extraordinary – aliens, mind control, angels and demons – and the conversation often jumps from topic to topic with little logical coherence.  It is common to hear new words in these conversations, or old words used in new and idiosyncratic ways.  “I'm just spread on Bratteo's twist”, a person with schizophrenia once told me, an apparent reference to a recent stay in a psychiatric hospital in Brattleboro, Vt.

The inner experience of schizophrenia seems to be primarily that of fear.  Schizophrenics have bizarre, often paranoid thoughts in their heads – aliens are thinking my thoughts, the hospital wants to tie me up and give me experimental medications, the landlady is sneaking into my room to steal my belongings, the Devil wants to make me one of his angels.  The schizophrenic seems convinced these things are real, and it must be terrifying to see the world in this way.  Add auditory and/or tactile hallucinations – voices telling me that I am no good, or feeling bugs crawling on my skin – can only increase the level of inner apprehension.  To even the healthiest of us, the world often seems cruel and uncaring, and painfully beyond our control.  Couple that difficult reality with hallucinations and bizarre delusions, and the experience of schizophrenia must approximate a living nightmare.  

Yet for all the attention given to hallucinations and delusional thinking, perhaps the most damaging of the features of schizophrenia is the one that receives the least attention.  Schizophrenia is also characterized by what the psychiatrists call the “negative symptoms”: manifested by a lack of affect, a lack of motivation, a lack of decision-making, a lack of interest and enthusiasm for the world around them.  Hallucinations and bizarre behaviors are often what brings the patient to the attention of mental health workers, because they are dramatic.  Hallucinations and bizarre behaviors can be corrected with anti-psychotic medication, while the negative symptoms do not respond to any medication.  So commonly, the older treated schizophrenic patient will stop exhibiting the wild hallucinations and behaviors, and turns into a burnt-out shell of a person, seemingly without ambition or choice or resolution, speaking little, moved mostly by outside forces and with little evidence of any internal volition.  This passivity and seeming loss of self will is a common attribute of schizophrenia and the strongest and most long-lasting feature of the disorder.

Schizophrenia effects somewhere between 0.5 – 1.0% of the population.  It effects men and women equally, and it occurs at similar rates in all ethnic groups.  Schizophrenia is fairly evenly distributed around the world, in both western industrialized nations and in non-industrialized third-world countries.  It is a condition that appears to be as old as mankind itself, with references found back to the beginnings of written history.  Schizophrenia typically begins in adolescence or early adulthood: a common story is that of a young person going off to college but being unable to continue because of poor grades and increasingly erratic behaviors.  Once past age 40, a new diagnosis of schizophrenia is rare

Since the 1960's, the primary treatment for schizophrenia has been anti-psychotic medications.  Most of the anti-psychotic medications have some effect on the level of dopamine, a chemical in the brain.  The theory is that taking the medication corrects the changes in brain chemistry that is thought to cause schizophrenia.  A variety of these anti-psychotic medications are now available.  They all have some degree of effectiveness at reducing the severity of the hallucinations and delusional thinking that characterizes schizophrenia.  Sadly, these medications also have strong and disturbing side effects.  Worse yet, the anti-psychotic medications are only effective at reducing symptoms, they do not cure the disease.

 The search for better treatments for schizophrenia has led scientists to consider alternative explanations for the phenomenon of schizophrenia.  What if schizophrenia is not a metabolic disorder that alters brain chemistry?  A variety of evidence now points to an infectious organism as a possible cause of schizophrenia: Toxoplasma gondii, the cause of toxoplasmosis in humans.

Toxoplasma gondii (T. gondii) is a protozoan parasite, a motile, single-celled organism that requires a host animal in which to reproduce.  T. gondii has two phases to its life cycle.  The sexual phases of the life cycle takes place only in cats, which makes domestic and wild cats the primary host for T. gondii.  The asexual part of the life cycle can take place in other mammals including cats, mice, birds, and humans.  Rodents are the typical intermediate host for T. gondii.  In rodents, the T. gondii bradyziotes form cysts within the muscles and brain.  When a cat eats an infected rodent, the parasite enters the cat through the GI tract and undergoes sexual reproduction: the bradyzoites differentiate into gametocytes, which fuse to form a zygote, which then matures into an oocyst.  Oocysts are shed in cat feces.  The life cycle of T. gondii is completed when an intermediary host comes into contact with cat feces and the oocysts are ingested, and bradyzoites are form in the host tissues.

Humans become infected with T. gondii in a couple of different ways.  Humans can ingest toxoplasma bradyzoites by eating improperly cooked meat.  Farm livestock can be intermediary hosts for T.gondii, and have toxoplasma cysts in their muscles.  If a human eats improperly prepared meat from an infected animal, the person can become infected.  Humans can also acquire toxoplasma through accidental contact with cat feces, while handling a cat, while cleaning the cat litter box, or when the neighborhood cat deposits oocysts in your garden.  Toxoplasma can also be transmitted during pregnancy from an infected mother to her unborn child.

It is estimated that over 20% of Americans (more than 60 million people) carry the toxoplasma organism inside them.  For most adults with a fully-functioning immune system, getting infected with toxoplasma is entirely asymptomatic or it might result in a mild flu-like illness that lasts a couple of weeks and then goes away.  However, the toxoplasma organisms remains in the body in an inactive state.  For people with a compromised immune system (i.e. has AIDS or is receiving immunosuppressant medications for a medical condition), a new infection with toxoplasma may cause a severe illness consisting of fever, nausea, headache, confusion, loss of coordination, and seizures.  Persons who were previously infected with toxoplasma and then later become immunosuppressed can have a reactivation of their infection, with symptoms varying from mild to severe.

Women who acquire a new infection with toxoplasma during pregnancy can pass the infection to their child in utero.  Such congenital infections may cause a miscarriage, or a stillborn birth.  Children infected in utero may show few or no signs of infection at birth, but may develop neurological problems later on in life, including eye and vision problems, seizure disorders, mental retardation, and/or other mental disabilities.  

So infection with toxoplasma results in a variety of disorders of the nervous system, in both rodents and humans.  We know that infection with toxoplasma causes behavioral changes in mice.  Mice infected with toxoplasma show evidence of impairments of learning and memory.  Rodents infected with T. gondii show problems with motor coordination.  Rodents infected with T. gondii show increased movements, and show reduced fear around cats and cat smells.  Indeed, infected mice seem to be drawn to the cat, a possible evolutionary strategy that furthers the reproduction, transmission, and spread of toxoplasma.

In addition to the neurological symptoms described above following new infections in adults and congenital infections in children, infection with toxoplasma has been linked to changes in psychological function in humans.  Humans with evidence of previous toxoplasma infections have been show to perform worse on tests of immediate and delayed memory, and on tests of attention, and have delayed reaction times.  Toxoplasmosis has also been linked to psychiatric illness in humans.  In a study of 114 people with known toxoplasmosis, 24 were found to have symptoms of psychiatric illness (psychosis, paranoia, or “psychic alteration”).  Psychiatric symptoms were also noted in two people who got toxoplasmosis while working in a toxoplasma lab, including difficulty concentrating, having difficulty holding a conversation, feeling disembodied, delusions, and hallucinations.  

People with a fully-functioning immune system will make antibodies in response to infection with toxoplasma.  So if toxoplasma is the cause of schizophrenia, it should be possible to find antibodies to toxoplasma in the blood of schizophrenics.  Many studies have found toxoplasma antibodies in patients with schizophrenia.  Since the 1950's, there have been over 70 studies looking for toxoplasma antibodies in patients with schizophrenia.  When the data from some of these studies was lumped together, it showed that a person with toxoplasma antibodies was over 2.7 times more likely to have a diagnosis of schizophrenia than a person without toxoplasma antibodies.  In an intriguing study of military personnel in whom blood specimens were available in the previous eleven years, people diagnosed with schizophrenia were compared to “normal” control subjects.  Among the subjects with schizophrenia, marked increases in toxoplasma antibodies were found prior to the onset of the illness.

And then there are the intriguing results of studies using different drugs.  There was a study of rats recently  infected with toxoplasma and then treated with haloperidol (Haldol, a powerful anti-psychotic medication).  The treatment with haloperidol reversed the behavioral effects of recent toxoplasma infection in these rats.  Anti-psychotic medications used in the treatment of schizophrenia have also been shown to inhibit the growth of toxoplasma in petri dishes.  In some cases, the anti-psychotic medications were more effective at inhibiting the growth of toxoplasma than trimethoprim, the standard treatment for toxoplasmosis.  And there have been studies in which schizophrenics have been given the anti-microbial agents used in the treatment of toxoplasmosis.  One study showed improvement in both positive and negative symptoms in patients receiving trimethoprim along with an anti-psychotic medication: previously, negative symptoms have not been shown to respond to any anti-psychotic treatments.  Other studies of the effectiveness of anti-microbial agents used in toxoplasmosis as a treatment for schizophrenia are currently underway.

So a variety of evidence suggests that toxoplasma might be the cause of schizophrenia: 1) infection with toxoplasma is known to cause neurological problems and strange behaviors in both rodents and humans; b) recent infection with toxoplasma has been documented to cause psychiatric symptoms in humans; c) people who have documented toxoplasma infections are more likely have a diagnosis of schizophrenia than those without toxoplasma infection; d) medications used in the treatment of schizophrenia show some effective at inhibiting the growth of toxoplasma; and e) anti-toxoplasma drugs show some effectiveness in treating the symptoms of schizophrenia.  At this time, the evidence suggesting toxoplasma is the cause of schizophrenia is stronger than the evidence that a disorder of dopamine metabolism is the cause of schizophrenia.  

This is terribly exciting for a number of reasons.  If toxoplasma is indeed the true cause of schizophrenia, this finding would point the way to new treatments for schizophrenia.  It is possible that such treatments could for the first time actually cure the disease, rather than simply reduce the severity of the symptoms.  This would be a God-send to the millions of schizophrenics around the world.  And a cure for schizophrenia would completely change how we view the disease.  No longer would we regard people with schizophrenia as hopeless oddballs to be avoided, but as normal people who had the misfortune to catch an infection, and perhaps be made whole again.  The stigma of mental illness would change forever.  

This is a future we can all eagerly look forward to.  

Extended (Optional)

Originally posted to Hugh Jim Bissell on Wed Jul 11, 2012 at 03:24 PM PDT.

Also republished by Mental Health Awareness.

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