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Science 301 (5631): 386-389

Copyright © 2003 by the American Association for the Advancement of Science

Influence of Life Stress on Depression: Moderation by a Polymorphism in the 5-HTT Gene

Avshalom Caspi,1,2 Karen Sugden,1 Terrie E. Moffitt,1,2* Alan Taylor,1 Ian W. Craig,1 HonaLee Harrington,2 Joseph McClay,1 Jonathan Mill,1 Judy Martin,3 Antony Braithwaite,4 Richie Poulton3

Abstract: In a prospective-longitudinal study of a representative birth cohort, we tested why stressful experiences lead to depression in some people but not in others. A functional polymorphism in the promoter region of the serotonin transporter (5-HT T) gene was found to moderate the influence of stressful life events on depression. Individuals with one or two copies of the short allele of the 5-HT T promoter polymorphism exhibited more depressive symptoms, diagnosable depression, and suicidality in relation to stressful life events than individuals homozygous for the long allele. This epidemiological study thus provides evidence of a gene-by-environment interaction, in which an individual's response to environmental insults is moderated by his or her genetic makeup.

1 Medical Research Council Social, Genetic, and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College London, PO80 De Crespigny Park, London, SE5 8AF, UK. 2 Department of Psychology, University of Wisconsin, Madison, WI 53706, USA. 3 Dunedin School of Medicine, 4 Department of Pathology, University of Otago, Dunedin, New Zealand.

* To whom correspondence should be addressed. E-mail: t.moffitt{at}iop.kcl.ac.uk

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