Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene.
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.
Caspi
Avshalom
A
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.
Sugden
Karen
K
Moffitt
Terrie E
TE
Taylor
Alan
A
Craig
Ian W
IW
Harrington
HonaLee
H
McClay
Joseph
J
Mill
Jonathan
J
Martin
Judy
J
Braithwaite
Antony
A
Poulton
Richie
R
D000328:Adult; D000483:Alleles; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002649:Child Abuse; D003863:Depression / Q000209:etiology / Q000235:genetics*; D003866:Depressive Disorder / Q000209:etiology / Q000235:genetics*; D004198:Disease Susceptibility; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D008995:Monoamine Oxidase / Q000235:genetics; D009419:Nerve Tissue Proteins; D011110:Polymorphism, Genetic; D011336:Probability; D011401:Promoter Regions, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins; D013315:Stress, Psychological / Q000235:genetics*; D013406:Suicide, Attempted
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D008995:Monoamine Oxidase