Expression and Methylation of <i>BDNF</i> in Human Schizophrenia Brain

Objective: To examine the combined effect of the <i>BDNF</i> Val66Met (rs6265) polymorphism and <i>BDNF</i> DNA methylation on transcriptional regulation of the <i>BDNF</i> gene. Methods: DNA methylation profiles were generated for CpG sites proximal to Val66Met, within <i>BDNF</i> promoter I and exon V for prefrontal cortex samples from 25 schizophrenia and 25 control subjects. Val66Met genotypes and <i>BDNF</i> mRNA expression data were generated by transcriptome sequencing. Expression, methylation and genotype data were correlated and examined for association with schizophrenia. Results: There was 43% more of the <i>BDNF</i> V-VIII-IX transcript in schizophrenia samples. <i>BDNF</i> mRNA expression and DNA methylation of seven CpG sites were not associated with schizophrenia after accounting for age and PMI effects. <i>BDNF</i> mRNA expression and DNA methylation were not altered by Val66Met after accounting for age and PMI effects. DNA methylation of one CpG site had a marginally-significant positive correlation with mRNA expression in schizophrenia subjects. Conclusion: Schizophrenia risk was not associated with differential <i>BDNF</i> mRNA expression and DNA methylation. A larger age-matched cohort with comprehensive clinical history is required to accurately identify the effects of genotype, mRNA expression and DNA methylation on schizophrenia risk.