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NARSAD Researchers Identify Specific Genes and Family Traits Linked to Schizophrenia, Bipolar Disorder and Depression
Date:5/30/2008

including keeping levels of the amino acid homocysteine low. When homocysteine levels are too high, this interferes with the functioning of receptors located all over the brain -- called NMDA ( N-methyl-D-aspartate) receptors -- that are critical to learning, memory, brain development, and general neural processing.

However, what causes low folate in people with schizophrenia is still open to question. One reason, confirmed by epidemiological studies, is poor dietary intake. Based on examining two major famines in the 20th century -- the Dutch Hunger Winter of 1944-45 brought about by the Nazi occupation in World War II and the Chinese famine in 1959-61 -- scientists found that the incidence of schizophrenia among children born to women who were pregnant during these famines increased two-fold.

But in most cases, starvation is not the problem. That is why Dr. Goff's team looked for other causes, including two genes: GCPII (glutamate carboxypeptidase II), which controls the absorption of folate and may be deficient in people with schizophrenia, and MTHFR (methylenetetrahydrofolate reductase), which activates folate for use in the brain. Using this information, Dr. Goff and his colleagues are recruiting patients for a large trial to determine whether folate supplementation will help individuals affected by these genes, many of whom have treatment-resistant psychotic symptoms. Funded by the National Institute of Mental Health, this double-blind study will follow 150 patients with schizophrenia at three sites over a 16-week period.

"Schizophrenia is a prevalent and costly disorder and can be very difficult to treat. This is especially true for the estimated 30 percent of patients with treatment-resistant psychotic symptoms, who may also experience social withdrawal, apathy, and depression," reports Dr. Goff. "Having these new data will validate whether folate, which is known to be very safe, is an effective way to improve outcomes for people with s
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