Epigenetic Regulation of BDNF in Major Depression
Condition: Major Depressive Disorder
MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Major
Study type: Observational

Summary: 
      The investigators will (1) detect the associations between brain-derived neurotrophic factor
      (BDNF) DNA methylation, histone modification, depressive symptoms, suicidal behavior and
      antidepressant responses in major depressive disorder (MDD) patients, (2) check the
      correlation between blood BDNF protein and RNA and BDNF rs6265 gene, and (3) discuss the
      possible mechanisms of epigenetic regulation of BDNF in Taiwanese major depressive patients.
    

Detailed description: 
      Brain-derived neurotrophic factor (BDNF) had been chosen as a candidate gene for a
      development of major depressive disorder (MDD). 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 the past studies, the investigators had found that major depressive women had lower serum
      BDNF protein levels than healthy controls, and their BDNF levels became significantly
      increased after antidepressant treatments. In addition, some authors had found that reduced
      expression of BDNF was noted in postmortem brain of completed suicide subjects. Suicidal
      major depressive patients also had lower plasma BDNF levels than non-suicidal major
      depressive patients. These findings suggested that BDNF might play an important role in the
      suicidal behavior.

      However, in past studies, the results did not fully explain why major depressive patients
      with same genotypes had different clinical expression, including the severity of depression,
      with/without suicide, and the treatment response. Recently, some papers found that there were
      relationships between epigenetic regulation, including DNA methylation and histone
      modification, and psychopathology of major depression. Therefore, we try to investigate the
      relationships between epigenetic regulation of BDNF and major depression.
    

Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        This 2-year study will be conducted in our clinical setting. By a semi-structured interview
        for DSM-IV criteria, a total of 160 subjectes (80 healthy controls and 80 patients with
        major depression) will be recruited in this study. In the first year (recruiting 40 healthy
        controls and 40 patients with major depression), the data of BDNF DNA methylation in all
        subjects will be collected. In the second year (recruiting another 40 healthy controls and
        40 patients with major depression), the data of BDNF histone modification in all subjects
        will be collected and the mechanism of epigenetic regulation of BDNF in major depression
        will be discussed.
      
Biospecimen description: 
      Blood
    
Keywords: Major depression; BDNF; DNA methylation; Histone modification