Negative association between DNA methylation in brain-derived neurotrophic factor exon VI and left superior parietal gyrification in major depressive disorder

Objective: We have recently reported significantly higher DNA methylation in brain-derived neurotrophic factor (BDNF) exon VI in major depressive disorder (MDD). This study aimed to investigated cortical changes and their associations with DNA methylations in BDNF exon VI in MDD.Methods: Data of 93 patients with MDD and 59 controls were involved in statistics. General linear regressions (GLM) were performed to analyze thickness and gyrification changes in MDD and their association with DNA methylation in BDNF exon VI in patients with MDD and controls.Results: Significantly decreased cortical thickness (CT) in left lateral orbitofrontal cortex (LOFC), left superior temporal lobe (ST) and right frontal pole (FP) and decreased local gyrification index (lGI) in left superior parietal lobe (SP) were found in MDD. The associations between DNA methylation in 3 CpG sites in BDNF exon VI and lGI in left SP were significantly different in patients and controls. DNA methylations in BDNF132 (beta = -0.359, P < 0.001), BDNF137 (beta = -0.214, P = 0.032), and BDNF151 (beta = -0.223, P = 0.025) were significantly negatively associated with lGI in left SP in MDD.Conclusion: The negative association between BDNF exon VI methylation and lGI in left SP might imply a po-tential epigenetic marker associated with cortical gyrification reduction in patients with MDD.