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The Long and the Short of It: Associations Between 5-HTT Genotypes and Coping With Stress

From the School of Psychiatry (K.W., J.E.S., A.W.F., D.H.-P., P.B.M., G.P.), University of New South Wales and Black Dog Institute, Sydney, Australia; Garvan Institute of Medical Research (P.R.S.), Sydney; University of New South Wales, Sydney; and Prince of Wales Medical Research Institute, Sydney, Australia.

Address correspondence and reprint requests to Kay Wilhelm, Level 4 De Lacey Building, St Vincent's Hospital, Darlinghurst, NSW, Australia, 2032. E-mail: kwilhelm{at}stvincents.com.au

Objective: To examine whether the strategies people use to cope with stress were associated with differing serotonin transporter (5-HTT) genotypes. The short (s) variant of the 5-HTT promoter polymorphism has been associated with an increased likelihood of depression after significant life stress and greater emotional reactivity to fear-invoking stimuli.

Methods: Coping strategies were assessed within a longitudinal study in 1993. Ten years later, genomic DNA was obtained for 127 participants and genotypes for the 5-HTT promoter polymorphism were determined. Coping strategies were grouped into coping scales and also using an exploratory factor analysis. Using ordinal regression, associations were then examined between the coping scales and the 5-HTT genotype and gender.

Results: The short variant of the 5-HTT promoter polymorphism was associated with the use of fewer problem-solving strategies. This genotype effect differed significantly between the sexes and was greatest for males.

Conclusions: Our results indicate that coping is influenced by 5-HTT genotype, gender, and their interaction. We raise the possibility that a gene-related disposition to greater emotional reactivity may preclude those with the short variant of the 5-HTT promoter polymorphism from drawing on problem-solving strategies to deal with stress.

Key Words: serotonin transporter gene • 5-HTT • genotype • promoter polymorphism • coping • depression

Abbreviations: 5-HTT = serotonin transporter; SCL6A4 = serotonin transporter gene; MD = major depression; ABM = antidepressive behavior measure; CUS = coping under stress.