title: A longitudinal study of SLC6A4 DNA promoter methylation and poststroke depression.
abstract: Serotonin transporter gene (SLC6A4) has been shown to play an important role in the pathophysiology of mood disorders including poststroke depression (PSD). SLC6A4 expression is influenced by DNA methylation status and the SLC6A4 linked promoter region (5-HTTLPR) polymorphism. This study aimed to investigate whether SLC6A4 methylation status was associated with depression ascertained at two weeks and one year after stroke taking into account the 5-HTTLPR polymorphism. A total of 286 patients were evaluated two weeks after stroke, and 222 (78%) were followed one year later. Depression was diagnosed according to DSM-IV criteria, and depression severity was assessed by the Hamilton Depression Rating Scale (HAMD) at each evaluation point. The effects of SLC6A4 methylation status on PSD status and HAMD scores were investigated using multivariate logistic regression models and partial correlation tests, respectively. Analyses were repeated after stratification by 5-HTTLPR genotype groups ('l/l or l/s' and 's/s'). Higher SLC6A4 promoter methylation status was independently associated with PSD both at 2 weeks and more prominently at 1 year after stroke, and was significantly associated with the worsening of depressive symptoms over one year. These findings were significant only in the presence of the 5-HTTLPR s/s genotype. SLC6A4 methylation profile was supported as a potential diagnostic and prognostic biomarker for PSD; associations with SLC6A4 methylation status may represent a target for drug development.
authors.affiliation: Department of Psychiatry, Chonnam National University Medical School, 160 Baekseoro, Dong-Ku, Gwangju 501-746, South Korea. Electronic address: jmkim@chonnam.ac.kr.
authors.forename: Jae-Min
authors.initials: JM
authors.lastname: Kim
authors.forename: Robert
authors.initials: R
authors.lastname: Stewart
authors.forename: Hee-Ju
authors.initials: HJ
authors.lastname: Kang
authors.forename: Sung-Wan
authors.initials: SW
authors.lastname: Kim
authors.forename: Il-Seon
authors.initials: IS
authors.lastname: Shin
authors.forename: Hye-Ran
authors.initials: HR
authors.lastname: Kim
authors.forename: Myung-Geun
authors.initials: MG
authors.lastname: Shin
authors.forename: Joon-Tae
authors.initials: JT
authors.lastname: Kim
authors.forename: Man-Seok
authors.initials: MS
authors.lastname: Park
authors.forename: Ki-Hyun
authors.initials: KH
authors.lastname: Cho
authors.forename: Jin-Sang
authors.initials: JS
authors.lastname: Yoon
mesh_terms: D000368:Aged; D019175:DNA Methylation / Q000502:physiology*; D003863:Depression / Q000209:etiology / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012720:Severity of Illness Index; D020521:Stroke / Q000150:complications / Q000235:genetics / Q000523:psychology*; D014057:Tomography, X-Ray Computed
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins
keywords: DNA methylation; Depression; Genetic association study; SLC6A4; Stroke