Original article| Volume 60, ISSUE 7, P671-676, October 01, 2006

Early Family Environment, Current Adversity, the Serotonin Transporter Promoter Polymorphism, and Depressive Symptomatology


      Mixed evidence has suggested that homozygous carriers of the short allele (s/s) of the serotonin transporter gene-linked polymorphic region (5-HTTLPR) may be at increased risk for depression, if they have also been exposed to early or current adversity/stress. We address this debate by examining the relation of a stressful early family environment, recent adversity/stress, and the 5-HTTLPR to depressive symptomatology in a normal sample.


      A nonclinical sample of 118 young adult men and women completed assessments of early family environment, recent stressful events, psychosocial resources, and psychological distress, including depressive symptomatology. The 5-HTTLPR was genotyped using a standard protocol with DNA extracted from oral fluid.


      A stressful early family environment was significantly related to depressive symptomatology. In addition, gene-by-environment (G×E) interactions were observed between the 5-HTTLPR and both early family environment and current adversity/stress. Individuals homozygous for the short allele had greater depressive symptomatology if they had experienced early or recent adversity but significantly less depressive symptomatology if they reported a supportive early environment or recent positive experiences, compared with participants with the s/l or l/l genotype.


      Early or current environment, in conjunction with the serotonin transporter polymorphism, predicts depressive symptomatology.

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        • Beck A.T.
        • Ward C.H.
        • Mendelson M.
        • Mock J.
        • Erbaugh J.
        An inventory for measuring depression.
        Arch Gen Psychiatry. 1961; 4: 561-571
        • Caspi A.
        • Sugden K.
        • Moffitt T.E.
        • Taylor A.
        • Craig I.W.
        • Harrington H.
        • et al.
        Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene.
        Science. 2003; 301: 386-389
        • Eley T.
        • Sugden K.
        • Corsico A.
        • Gregory A.
        • Sham P.
        • McGuffin P.
        • et al.
        Gene-environment interaction analysis of serotonin system markers with adolescent depression.
        Mol Psychiatry. 2004; 9: 908-915
        • Felitti V.J.
        • Anda R.F.
        • Nordenberg D.
        • Williamson D.F.
        • Apitz A.M.
        • Edwards V.
        • et al.
        Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults.
        Am J Prev Med. 1998; 14: 245-258
        • Gelernter J.
        • Kranzler H.
        • Cubells J.F.
        Serotonin transporter protein (SLC6A4) allele and haplotype frequencies and linkage disequilibria in African- and European-American and Japanese populations and in alcohol-dependent subjects.
        Hum Genet. 1997; 101: 243-246
        • Gillespie N.
        • Whitefield J.
        • Williams B.
        • Heath A.
        • Martin N.
        The relationship between stressful life events, the serotonin (5-HTTLPR) genotype and major depression.
        Psychol Med. 2005; 35: 101-111
        • Glatz K.
        • Mossner R.
        • Heils A.
        • Lesch K.P.
        Glucocorticoid-regulated human serotonin transporter (5-HTT) expression is modulated by the 5-HTT gene-promotor-linked polymorphic region.
        Neurochemistry. 2003; 86: 1072-1078
        • Goldberg L.
        A broad-bandwidth, public-domain, personality inventory measuring the lower-level facets of several five-factor models.
        Personality Psychol Europe. 1999; 7: 7-28
        • Grabe H.
        • Lange M.
        • Wolff B.
        • Volzke H.
        • Lucht M.
        • Freyberger H.
        • et al.
        Mental and physical distress is modulated by a polymorphism in the 5-HT transporter gene interacting with social stressors and chronic disease burden.
        Mol Psychiatry. 2005; 10: 220-234
        • Kaufman J.
        • Yang B.-Z.
        • Douglas-Palumberi H.
        • Houshyar S.
        • Lipschitz B.
        • Krystal J.
        • Gelernter J.
        Social supports and serotonin transporter gene moderate depression in maltreated children.
        Proc Natl Acad Sci. 2004; 101: 17316-17321
        • Kendler K.
        • Kuhn J.
        • Vittum J.
        • Prescott C.
        • Riley B.
        The interaction of stressful life events and a serotonin transporter polymorphism in the prediction of episodes of major depression.
        Arch Gen Psychiatry. 2005; 62: 529-535
        • Laland K.
        The mathematical modeling of human culture and its implications for psychology and the human sciences.
        Br J Psychol. 1993; 84: 145-169
        • Lehman B.J.
        • Taylor S.E.
        • Kiefe C.I.
        • Seeman T.E.
        Relation of childhood socioeconomic status and family environment to adult metabolic functioning in the CARDIA study.
        Psychosom Med. 2005; 67: 846-854
        • Lesch K.P.
        • Bengel D.
        • Heils A.
        • Sabol S.Z.
        • Greenberg B.D.
        • Petri S.
        • et al.
        Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region.
        Science. 1996; 274: 1527-1531
        • Manuck S.B.
        • Flory J.D.
        • Ferrell R.E.
        • Muldoon M.F.
        Socio-economic status covaries with central nervous system serotonergic responsivity as a function of allelic variation in the serotonin transporter gene-linked polymorphic region.
        Psychoneuroendocrinology. 2004; 29: 651-668
        • Markus H.R.
        • Kitayama S.
        Culture and the self: Implications for cognition, emotion, and motivation.
        Psychol Rev. 1991; 98: 224-253
        • Pearlin L.I.
        • Schooler C.
        The structure of coping.
        Health Soc Behav. 1978; 19: 2-21
        • Rosenberg M.
        Society and the adolescent self-image. Princeton University Press, Princeton, NJ1965
        • Scheier M.F.
        • Carver C.S.
        Optimism, coping, and health: assessment and implications of generalized outcome expectancies.
        Health Psych. 1985; 4: 219-247
        • Schuster T.L.
        • Kessler R.C.
        • Aseltine R.H.
        Supportive interactions, negative interactions and depressed mood.
        Am J Community Psychol. 1990; 18: 423-438
        • Spielberger C.D.
        • Gorsuch R.L.
        • Lushene R.D.
        Manual for the State-Trait Anxiety Inventory. Consulting Psychologists Press, Palo Alto, CA1970
        • Suomi S.J.
        Attachment in rhesus monkeys.
        in: Cassidy J. Shaver P. Handbook of Attachment: Theory, Research, and Clinical Applications. Guilford Press, New York1999
        • Surtees P.G.
        • Wainwright N.W.
        • Willis-Owen S.A.
        • Luben R.
        • Day N.E.
        • Flint J.
        Social adversity, the serotonin transporter (5-HTTLPR) polymorphism and major depressive disorder.
        Biol Psychiatry. 2006; 59: 224-229
        • Taylor S.E.
        • Lerner J.
        • Sherman D.K.
        • Sage R.
        • McDowell N.
        Are self-enhancing cognitions associated with healthy or unhealthy biological profiles?.
        J Pers Soc Psychol. 2003; 85: 605-615
        • Taylor S.E.
        • Lerner J.S.
        • Sage R.M.
        • Lehman B.J.
        • Seeman T.E.
        Early environment, emotions, responses to stress, and health.
        J Pers. 2004; 72: 1365-1393
        • Wilhelm K.
        • Mitchell P.
        • Niven H.
        • Finch A.
        • Wedgwood L.
        • Schimone A.
        • Blair I.
        • et al.
        Life events, first depression onset and the serotonin transporter gene.
        Br J Psychiatry. 2006; 188: 210-215