title: Association between reduced white matter integrity in the corpus callosum and serotonin transporter gene DNA methylation in medication-naive patients with major depressive disorder.
abstract: 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, P<0.01). 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.
authors: Department of Psychiatry, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea.
authors: E
authors: E
authors: Won
authors: Department of Brain and Cognitive Engineering, Korea University, Seoul, Korea.
authors: S
authors: S
authors: Choi
authors: Department of Biomedical Science, Korea University, Seoul, Korea.
authors: J
authors: J
authors: Kang
authors: Department of Biomedical Science, Korea University, Seoul, Korea.
authors: A
authors: A
authors: Kim
authors: Department of Psychiatry, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea.
authors: K-M
authors: KM
authors: Han
authors: Department of Medical Bioscience, Graduate School, Soonchunhyang University, Bucheon, Korea.
authors: H S
authors: HS
authors: Chang
authors: Brain Convergence Research Center, Anam Hospital, Korea University Medical Center, Seoul, Korea.
authors: W S
authors: WS
authors: Tae
authors: Department of Radiology, Korea University Medical Center, Korea University College of Medicine, Seoul, Korea.
authors: K R
authors: KR
authors: Son
authors: Department of Psychiatry, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea.
authors: S-H
authors: SH
authors: Joe
authors: Department of Psychiatry, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea.
authors: M-S
authors: MS
authors: Lee
authors: Department of Psychiatry, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea.
authors: B-J
authors: BJ
authors: Ham
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003337:Corpus Callosum / Q000000981:diagnostic imaging*; D019175:DNA Methylation; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging / Q000235:genetics*; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D008297:Male; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D066127:White Matter / Q000000981:diagnostic imaging*
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins