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Influence of Life Stress on Depression: Moderation by a Polymorphism in the 5-HTT Gene
Avshalom Caspi,1,2Karen Sugden,1Terrie E. Moffitt,1,2*Alan Taylor,1Ian W. Craig,1HonaLee Harrington,2Joseph McClay,1Jonathan Mill,1Judy Martin,3Antony Braithwaite,4Richie Poulton3
In a prospective-longitudinal study of a representative birthcohort, we tested why stressful experiences lead to depressionin some people but not in others. A functional polymorphismin the promoter region of the serotonin transporter (5-HT T)gene was found to moderate the influence of stressful life eventson depression. Individuals with one or two copies of the shortallele of the 5-HT T promoter polymorphism exhibited more depressivesymptoms, diagnosable depression, and suicidality in relationto stressful life events than individuals homozygous for thelong allele. This epidemiological study thus provides evidenceof a gene-by-environment interaction, in which an individual'sresponse to environmental insults is moderated by his or hergenetic 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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