MONDAY, Oct. 24 (HealthDay News) -- Two new studies in Nature Neuroscience shed light on the complexities of genetic risk factors for schizophrenia. The genes encoding for the enzymes catechol-O-methyltransferase (COMT) and proline dehydrogenase (PRODH), which are affected in the rare chromosome 22 microdeletion syndrome (22q11.2), appear to play a central role in the development of some cases of psychosis.
In the first study, Doron Gothelf, M.D., of Stanford University School of Medicine, and colleagues followed 24 children with chromosome 22 deletion syndrome (22q11.2DS), who inherit only one good copy of the COMT gene. Some of the children had a high-activity version of the gene, while others had a low-activity polymorphism. During the prospective trial, 29.2% of the children with 22q11.2DS developed schizophrenia, which is a known risk of the disease, compared with 4.2% of a control group. However, patients with the low-activity COMT polymorphism had a greater decline in their prefrontal cortex and were at greater risk for a psychotic disorder than other patients.
A second study led by Marta Paterlini, M.D., of Columbia University in New York, examined the behavior in mice deficient for the enzyme proline dehydrogenase (PRODH), another gene found on chromosome 22 that is absent in 22q11.2DS. The increased dopaminergic hyperactivity seen in PRODH-deficient mice supports the hypothesis that this enzyme also plays a pivotal role in the neurodevelopmental pathways leading to psychotic disorders.
The findings suggest that an extreme deficiency in COMT activity is an "important" risk factor for the development of psychotic symptoms in adolescence, conclude Gothelf and colleagues.
Abstract
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