Gene Related To Brain Development And Function Plays Causal
Role In Schizophrenia
Study Finds
Main Category: Schizophrenia
News
Article Date: 17 Aug 2006 - 21:00pm (PDT)
According to a new study conducted by researchers at Mount Sinai School
of Medicine, variations of a gene related to brain development and
function--OLIG2--may play a causal role in the development of
schizophrenia, a hereditary psychiatric disorder with no known
biological cause. The study is published in the August 15 printed issue
of Proceedings of National Academy of Sciences.
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.