Epigenetic Regulation of Bdnf in Patients with Major Depression

BDNF (brain-derived neurotrophic factor) had been chosen as a candidate gene for a development of major depression. BDNF had been reported to have an important role on neuronal plasticity, axonal growth and connectivity, and participating in the local response to various types of neuronal stressors. BDNF also influences the differentiation of neurons. In past studies, we had found that major depressive women had lower serum BDNF protein levels than healthy controls and there were significantly increase in BDNF levels after the treatments of antidepressants. In addition, some authors had found that reduced expression of BDNF was noted in postmortem brain in suicide subjects and suicidal major depressive patients had lower plasma BDNF levels than non-suicidal major depressive patients. They suggested that BDNF might play an important role in the suicidal behavior. However, in past studies, the results did not explain why major depressive patients with same genotypes had different clinical expression, including the severity of depression, with/without suicide, and the treatment response. In recent, some papers found that there were relationships between epigenetic regulation and psychopathology of major depression, including DNAmethylation and histone modification. Therefore, we try to investigate the relationships between epigenetic regulation of BDNF and depression. A total 160 subjectes (80 health controls and 80 patients with major depression) will be recruited in this 2-year study. The first year (40 health controls and 40 major depression), the BDNF DNAmethylation in all subjects will be collected. The second year (40 health controls and 40 major depression), the BDNF histone modification in all subjects will be collected. In this proposal, we will (1) detect the associations between BDNF DNAmethylation (rs6265 gene and promoter IV area), histone modification, depressive symptoms, suicidal behavior and antidepressant responses in major depressive patients (2) check the correlation between blood BDNF protein and mRNA and BDNF rs6265 gene and promoter IV area (3) discuss the possible mechanisms of epigenetic regulation of BDNF in Taiwanese major depressive patients.

Project ID:PC9907-2509
External Project ID:NSC99-2628-B182-002-MY2