Previous evidence suggests that the serotonin transporter gene (SLC6A4) is associated with the structure of brain regions that are critically involved in dysfunctional limbic-cortical network activity associated with major depressive disorder (MDD). Diffusion tensor imaging (DTI) and tract-based spatial statistics were used to investigate changes in white matter integrity in patients with MDD compared with healthy controls. A possible association between structural alterations in white matter tracts and DNA methylation of the SLC6A4 promoter region was also assessed. Thirty-five medication-naive patients with MDD (mean age: 40.34, male/female: 10/25) and age, gender and education level matched 49 healthy controls (mean age: 41.12, male/female: 15/34) underwent DTI. SLC6A4 DNA methylation was also measured at five CpG sites of the promoter region, and the cell type used was whole-blood DNA. Patients with MDD had significantly lower fractional anisotropy (FA) values for the genu of the corpus callosum and body of the corpus callosum than that in healthy controls (family-wise error corrected, Po0.01). Significant inverse correlations were observed between SLC6A4 DNA methylation and FA (CpG3, Pearson's correlation: r = - 0.493, P = 0.003) and axial diffusivity (CpG3, Pearson's correlation: r = - 0.478, P = 0.004) values of the body of the corpus callosum in patients with MDD. These results contribute to evidence indicating an association between epigenetic gene regulation and structural brain alterations in depression. Moreover, we believe this is the first report of a correlation between DNA methylation of the SLC6A4 promoter region and white matter integrity in patients with MDD.
Bibliographical noteFunding Information:
This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2011-0023272), and the Korean Health Technology R&D Project, Ministry of Health and Welfare, Korea (HI12C0003). The funder had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript.
ASJC Scopus subject areas
- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
- Biological Psychiatry