Childhood Schizophrenia

Via twitter: the LA Times reports on a tragic case of childhood schizophrenia.

Doctors and other mental health experts don't fully understand the disease, which has no cure. Jani's extreme early onset has left them almost helpless. The rate of onset in children 13 and under is about one in 30,000 to 50,000. In a national study of 110 children, only one was diagnosed as young as age 6.
"Child-onset schizophrenia is 20 to 30 times more severe than adult-onset schizophrenia," says Dr. Nitin Gogtay, a neurologist at the National Institute of Mental Health who helps direct the children's study, the largest such study in the world on the illness.
"Ninety-five percent of the time they are awake these kids are actively hallucinating," Gogtay says. "I don't think I've seen anything more devastating in all of medicine."
For Jani's parents, the most pressing issue is where Jani should live. She has been on the UCLA psych ward -- where she was placed during an emergency -- since Jan. 16. The ward is not designed for long-term care.

Toxoplasmosis and You

Today's featured parasite is the stealthy and adaptable protozoan, Toxoplasma gondii.

This is the cat-litter bug that causes miscarriages and birth defects. The cat-loving parasite that lures rats to their deaths and causes traffic accidents. The latest schizophrenia suspect and a possible cause of epilepsy, psychosis, and migraines.

T. gondii may be making society rigid and neurotic, men more masculine, stupider, or more surly, and women more promiscuous. And if you think things are bad in the northern hemisphere, you should see the Brazilian strains.

About 16% 11% 33% of Americans are infected; infection rates are much higher in tropical countries (and France). Wikipedia tells the sad tale of Louis Wain, English cat artist, late-onset schizophrenic, and poster-child for the toxoplasmosis-schizophrenia connection.

T. gondii has its own book, conference, mugs and a blog, The Anti-Toxo, where you can follow mankind's losing battle with our one-celled masters.

Image by kqedquest. Some rights reserved.

Schizotypal Selection

Via John Hawks and the Four Stone Hearth Carnival of Anthropology: The Primate Diaries' explains Sapolsky's theory of selection for schizotypal personalities, possibly in shamans.

Several years ago Robert Sapolsky suggested that genes promoting schizophrenia may have been selected for in human evolution because some of them conferred benefits that outweighed the 1% of people worldwide that were disabled by the disorder. Like the sickle-cell trait that confers resistance to malaria (so long as you don’t receive two recessive alleles and develop full fledged sickle cell anemia) a partial schizophrenia may be beneficial in some way. He observed that relatives of schizophrenics have a high likelihood of “schizotypal personalities,” or a mild form of the disorder that just makes these people a little strange and allows them to see the world in a unique way. What if, he wondered, schizophrenia maintained itself in human populations because of selection for schizotypal personalites? As luck would have it, for a hundred years anthropologists had observed such individuals thriving in nearly every society they encountered: shamans.

Autism, Bipolar Disorder, and Schizophrenia

Via Gene Expression, a PNAS article that correlates susceptibility to 161 diseases, pairwise, with special attention to autism, bipolar disorder, and schizophrenia. They interpret the correlations as overlap in the genetic mechanisms of (susceptibility to) the various diseases.

Our analysis suggests that, instead of following the familiar model of ‘‘unique malady–unique (disjoint with others) set of broken genes’’ applicable to most Mendelian disorders (Fig. 2D), most complex phenotypes are probably rooted in genetic variation that is significantly shared (in either a competitive or cooperative manner) by multiple disease phenotypes (Fig. 2E).
Phenotypes of non-Mendelian disorders are often defined with a considerable degree of fuzziness, especially those that are neurological: it is not uncommon to define a neuropsychiatric disease phenotype as comprising, for example, at least five of a list of 10 symptoms (4). This fuzziness arises because, in many cases, the observed disease is a heterogeneous collection of multiple maladies that have partially similar symptoms and potentially different genetic causes. However, these genetically heterogeneous maladies are combined because of the history of disease identification and the incompleteness of our knowledge about the disease causes.
Our interpretation of genetic overlap among pairs of disorders does not exclude the possibility that one disorder can cause the other. For example, it is possible that comorbidity of autism (or schizophrenia, or bipolar disorder)with infectious and autoimmune maladies indicates that the neurodevelopmental disorder can be triggered by different developmental insults, including viral or bacterial infection, or an autoimmune disease launched by a benign allergen. Another possibility is that the same molecular features that make a child more susceptible to infection or to autoimmune attack have a pleiotropic effect on brain development and function.

For the full list of overlaps, see the appendices. Appendix 1 has more pretty pictures, while 4 and 5 have some easier-to-read tables. Here's the pretty picture for plague (click to enlarge):

A Gene for Schizophrenia

Via Gene Expression: EurekAlert! on a gene that causes schizophrenia:

Earlier research [at Mount Sinai and elsewhere] suggests that schizophrenia is associated with changes in myelin, the fatty substance or white matter in the brain that coats nerve fibers and is critical for the brain to function properly. Myelin is formed by a group of central nervous cells called oligodendrocytes, which are regulated by the gene oligodendrocyte lineage transcription factor 2 (OLIG2). Patients with schizophrenia are known to have insufficient levels of oligodendrocytes, however the source of this [deficiency] has not been identified, explains study co-author Joseph D. Buxbaum, PhD, the G. Harold and Leila Y. Mathers Research Professor of Geriatrics and Adult Development, Professor of Psychiatry and Neuroscience, and Co-Principal Investigator of the Siliva O. Conte Center for the Neuroscience of Mental Disorders.
Dr. Buxbaum and a team of Mount Sinai researchers collaborated with researchers from the Cardiff University School of Medicine in the United Kingdom to analyze DNA in blood samples taken from 673 unrelated patients with schizophrenia and compared their genetic information to 716 patients who did not have the disease. The controls were matched for age, sex, and ethnicity; none were taking medications at the time of the study.
The study showed that genetic variation in OLIG2 was strongly associated with schizophrenia. In addition, OLIG2 also showed a genetic association with schizophrenia when examined together with two other genes previously associated with schizophrenia--CNP and ERBB4--which are also active in the development of myelin. The expression of these three genes was also coordinated. Taken together the data support an etiological role for oligodendrocyte abnormalities in the development of schizophrenia.

Toxoplasma

Technovelgy speculates about Toxoplasma Parasite Mind Control in rats and people:

Oxford scientists discovered that the minds of the infected rats have been subtly altered. In a series of experiments, they demonstrated that healthy rats will prudently avoid areas that have been doused with cat urine. In fact, when scientists test anti-anxiety drugs on rats, they use a whiff of cat urine to induce neurochemical panic. However, it turns out that Toxoplasma-ridden rats show no such reaction. In fact, some of the infected rats actually seek out the cat urine-marked areas again and again. The parasite alters the mind (and thus the behavior) of the rat for its own benefit. [...]
Dr. Torrey got together with the Oxford scientists, to see if anything could be done about those parasite-controlled rats who were driven to hang around cat urine-soaked corners (waiting for cats). According to a recent press release, it turns out that haloperidol restores the rat's healthy fear of cat urine. In fact, antipsychotic drugs were as effective as pyrimethamine, a drug that specifically eliminates Toxoplasma.

From the press release from Imperial College London:

Research published today in Procedings of the Royal Society B, shows how the invasion or replication of the parasite Toxoplasma gondii in rats may be inhibited by using anti-psychotic or mood stabilising drugs.
The researchers tested anti-psychotic and mood stabilising medications used for the treatment of schizophrenia on rats infected with T. gondii and found they were as, or more, effective at preventing behaviourial alterations as anti-T. gondii drugs. This led them to believe that T. gondii may have a role in the development of some cases of schizophrenia.

Scanning for Schizophrenia

The Scotland Sunday Times reports on a new method to detect schizophrenia up to three years before onset.

Researchers at Edinburgh University believe their test — which measures IQ, memory, motor skills and verbal learning — can be used to take action against the illness, which typically strikes people aged between 17 and 30, from being triggered.