title: Psychosocial mechanisms of serotonin transporter's genetic polymorphism in susceptibility to major depressive disorder: mediated by trait coping styles and interacted with life events.
abstract: The mechanism of 5-HTT genetic polymorphisms related susceptibility of major depressive disorder (MDD) has not been fully understood. Two hundred MDD patients and 199 control subjects were included. A model of two binary logistical regressions with and without controlling for different psychosocial variables, was applied to investigate the possible mediation effects of psychosocial factors in contribution of 5-HTT polymorphisms in MDD development. These psychosocial variables included personality, trait coping style, life events and social support. Then, contribution of interactions between 5-HTT polymorphisms and psychosocial factors in MDD was investigated by a stepwise logistical approach. The results indicated a significant association of 5-HTT LPR with the MDD indicence, but not of VNTR genotype variances with the MDD incidence without counting effects of psychosocial factors. The ss genotype of LPR demonstrated 2.50 (95% CI: 1.11-5.62) times higher odds to develop MDD than ll genotype (p=0.026). After including psychosocial variables, the odds ratio of 5-HTT LPR ss to ll genotype dropped to 1.30 times (95% CI: 0.41-4.10) and became non-significant (p=0.658). While psychosocial variables all showed significant contributions to MDD susceptibility. Our data suggested an intermediator role of this psychosocial variable in LPR genetic pathogenesis of MDD. Whereas, 5-HTT VNTR could significantly affect MDD outcome by interacting with life events (p=0.043). In conclusion, 5-HTT LPR and VNTR polymorphisms could affect MDD susceptibility through mediation by trait coping styles and interaction with severe life events, respectively. The genetic information of 5-HTT can be potentially helpful for diagnosis and further therapy.
authors.affiliation: Department of Psychiatry, First Hospital of Shanxi Medical University Taiyuan 030001, Shanxi Province, China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, First Hospital of Shanxi Medical University Taiyuan 030001, Shanxi Province, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Sun
authors.affiliation: Department of Psychiatry, First Hospital of Shanxi Medical University Taiyuan 030001, Shanxi Province, China.
authors.forename: Zhifen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Psychiatry, First Hospital of Shanxi Medical University Taiyuan 030001, Shanxi Province, China.
authors.forename: Xinrong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Psychiatry, First Hospital of Shanxi Medical University Taiyuan 030001, Shanxi Province, China.
authors.forename: Chunxia
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Psychiatry, First Hospital of Shanxi Medical University Taiyuan 030001, Shanxi Province, China.
authors.forename: Kerang
authors.initials: K
authors.lastname: Zhang
keywords: Serotonin transporter; gene polymorphism; major depressive disorder; psychosocial factor