Clement Zai, Ph.D., Centre for Addiction and Mental Health
Posdoctoral Research Fellowship (2010): $100,000
Mentor: James Kennedy, M.D., Centre for Addition and Mental Health
GABA system genes and suicidal behavior in psychiatric disorders
Abstract: The key objectives of the proposed study are to investigate DNA polymorphisms in genes associated with the GABA neurotransmitter system for association with suicidal behavior, and to determine the potential functional significance of these polymorphisms. The applicant hypothesizes that selected GABA system genes will be associated with suicide risk, that DNA resequencing of these genes will reveal novel variants that will determine gene expression levels, and that combination of variants may interact to contribute to risk variants for suicide. This research will genotype SNPs across several GABAergic related genes, including GAD, the GABA transporter and three GABA receptor subunits. These genes were chosen based on previous associations with mood disorders. In addition, targeted multiplexed resequencing of the 10 kb region upstream of each of the five selected candidate genes will be conducted to identify variants within regions of these genes that might contribute to changes in gene expression. Two samples consist of bipolar patients and a third schizophrenics. One bipolar population has 352 subjects with 86 attempters, the second has 450 subjects and 122 attempters and the schizophrenic population has 231 subjects with 81 attempters. There are postmortem brain tissue samples from Brodman’s area 46 (Stanley Foundation) from 41 schizophrenic subjects (10 suicide) and 44 bipolar subjects (22 suicide). In addition, the investigator plans access to additional schizophrenic, bipolar and depressed brain tissue from the Harvard Brain collection and the Stanley Foundation brain collection.