Variations in a gene related to brain development and function called OLIG2 may play a causal role in development of schizophrenia through impairment in development of oligodendrocytes, the cells that produce myelin, according to an article published in the August 15 issue of the Proceedings of the National Academy of Sciences (USA).

Earlier research had suggested that schizophrenia is associated with changes in myelin, which is synthesized by oligodendrocytes. Development is 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 the deficiency has not been identified, said study co-author Joseph D. Buxbaum, PhD.

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 compare their genetic information to 716 patients without the disease. The controls were matched for age, sex, and ethnicity, and 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?genes that are also active in development of myelin.

The expression of the three genes was also coordinated. Taken together, the data support an etiological role for oligodendrocyte abnormalities in 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,” Buxbaum said. “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.”

Buxbaum added that as researchers further unravel the role of oligodendrocytes and myelin in schizophrenia, it is possible that medications such as those being developed for the treatment of multiple sclerosis?a disorder associated with breakdown of myelin?may have future impact in the treatment of schizophrenia.