A longitudinal study of BDNF promoter methylation and genotype with poststroke depression

Introduction: Brain derived neurotrophic factor (BDNF) has been shown to play an important role in the pathophysiology of mood disorders including poststroke depression (PSD). BDNF secretion is influenced by epigenetic and genetic profiles. This study aimed to investigate whether BDNF gene promoter methylation status and val66met polymorphism were associated with depression ascertained at two weeks and one year after stroke.

Methods: A total of 286 patients were evaluated two weeks after stroke, and 222 (78%) were followed one year later. Depression (major or minor depressive disorder) was diagnosed according to DSM-IV criteria, and classified into prevalent, persistent, and incident PSD according to presence at the two examinations. Depression severity was assessed by the Hospital Anxiety and Depression Scale-depression subscale and the Hamilton Depression Rating Scale. The effects of BDNF methylation status and genotype on PSD status were investigated using multivariate logistic regression models. The associations of BDNF methylation status and genotype with score on depression assessment scales were estimated using partial correlation tests and general linear models, respectively.

Results: Higher BDNF methylation status was independently associated with prevalent, persistent and particularly with incident PSD, and with worsening depressive symptoms over follow-up but not with baseline severity. The BDNF val66met polymorphism was independently associated with prevalent PSD, but not with persistent and incident PSD nor with depressive symptoms severity. No significant methylation-genotype interactions were found.

Limitations: Methylation status was investigated with limited area of the BDNF gene and sample size was relatively small.

Conclusions: A role for BDNF in PSD was supported, and associations with BDNF gene methylation status may represent a target for drug development.