John Strauss, M.D., M.Sc., Centre for Addiction and Mental Health, University of Toronto
Young Investigator Grant (2009): $85,000
Mentor: Arturas Petronis, M.D., Ph.D., University of Toronto
BDNF Promoter Methylation and Suicidal Behavior in Bipolar Disorder
Abstract: This research grant will investigate methylation patterns in the brain-derived neurotrophic factor (BDNF) gene. Published research has reported that the BDNF gene and its products have been associated with suicidal behavior. Several lines of evidence point to BDNF as a factor in mood disorders and specifically bipolar disorder illnesses, where there are greater percentages of suicides or attempts. Epigenetic factors may play a role and a mechanism for epigenetics is the modifications in gene expression that are controlled by heritable, but potentially reversible by changes in DNA methylation. Peripheral lymphocyte DNA methylation will be studied for genetic and epigenetic association with suicidal behavior. Two sources of variation at the BDNF locus will be analyzed: SNP variation (sequencing) and quantitative methylation using mass spectrometry. A subset of subjects of a genome-wide association study will be used for the lymphocyte samples. There will two sample groupings. Each will contain three separate subjects groups of 20 subjects each, for a total of 60 in both Sample I (bipolar depression with and without suicide attempts and matched health controls) and II (child-onset mood disorder bipolar depression prior to 17 years of age with and without suicide attempts and matched health controls). A deeper understanding of the genetic and neural substrates of behavior is essential for the next generation of preventive interventions, ranging from the role of biomarkers and endophenotypes in identifying those most in need of prevention to the longitudinal environmental sensitivity of neural systems.