title: Influence of FKBP5 polymorphism and DNA methylation on structural changes of the brain in major depressive disorder.
abstract: A single nucleotide polymorphism of rs1360780 in the FKBP5 gene is associated with a predisposition to developing major depressive disorder (MDD). We investigated the interactive effects of FKBP5 rs1360780 allelic variants, DNA methylation, and the diagnosis of MDD on structural changes of the entire brain. One hundred and fourteen patients with MDD and eighty-eight healthy controls underwent T1-weighted structural magnetic resonance imaging and FKBP5 rs1360780 genotyping, including DNA methylation of intron 7. We analyzed the volume of cortical and subcortical regions and cortical thickness using FreeSurfer. Significant genotype-by-diagnosis interactions were observed for volumes of the left pars triangularis, supramarginal gyrus, superior parietal lobule, right frontomarginal, and posterior midcingulate gyrus. The T allele was associated with significant volume reductions in these brain regions only in the MDD group except for the right posterior midcingulate gyrus. FKBP5 DNA methylation showed a positive correlation with the thickness of the right transverse frontopolar gyrus in the C allele homozygote group. Our findings suggest that the FKBP5 gene and its epigenetic changes could have influence on morphologic changes of several brain regions involved in emotion regulation, and that this process may be associated with the development of MDD.
authors.affiliation: Department of Psychiatry, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Kyu-Man
authors.initials: KM
authors.lastname: Han
authors.affiliation: Department of Psychiatry, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Eunsoo
authors.initials: E
authors.lastname: Won
authors.affiliation: Brain Convergence Research Center, Korea University Anam Hospital, Seoul, Republic of Korea.
authors.forename: Youngbo
authors.initials: Y
authors.lastname: Sim
authors.affiliation: Department of Biomedical Sciences, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: June
authors.initials: J
authors.lastname: Kang
authors.affiliation: Department of Psychiatry, Korea University Ansan Hospital, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Changsu
authors.initials: C
authors.lastname: Han
authors.affiliation: Department of Psychiatry, Korea University Ansan Hospital, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Yong-Ku
authors.initials: YK
authors.lastname: Kim
authors.affiliation: Department of Psychiatry, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Psychiatry, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sook-Haeng
authors.initials: SH
authors.lastname: Joe
authors.affiliation: Department of Psychiatry, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Min-Soo
authors.initials: MS
authors.lastname: Lee
authors.affiliation: Brain Convergence Research Center, Korea University Anam Hospital, Seoul, Republic of Korea.
authors.forename: Woo-Suk
authors.initials: WS
authors.lastname: Tae
authors.affiliation: Department of Psychiatry, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea.|Brain Convergence Research Center, Korea University Anam Hospital, Seoul, Republic of Korea.
authors.forename: Byung-Joo
authors.initials: BJ
authors.lastname: Ham
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D018899:CpG Islands; D019175:DNA Methylation; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D044127:Epigenesis, Genetic; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D005838:Genotype; D066128:Gray Matter / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D020641:Polymorphism, Single Nucleotide; D022021:Tacrolimus Binding Proteins / Q000235:genetics*; D055815:Young Adult; D000099159:Tacrolimus Binding Protein 5
chemical_list: D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5