Study Finds Gene Related To Brain Development And Function Plays Causal Role In 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.

"Multiple genes likely have a role in schizophrenia and there are probably many things happening in the brain of a schizophrenia patient," Dr. Buxbaum says. "The findings from this study help us tease out a potential biological cause that may be contributing to this debilitating illness. This study showed that OLIG2 has a causal etiological effect and these findings give us a stronger sense of where to look so we can develop more therapeutic targets for this very complex disease."

Dr. Buxbaum adds that as researchers further unravel the role of oligodendrocyte and myelin in schizophrenia, it is possible that medications like those being developed for the treatment of multiple sclerosis--a disorder associated with a breakdown of myelin--may have a future impact in the treatment of schizophrenia.