Association of a triallelic seroton in transporter gene promoter region (5-HTTLPR) polymorphism with stressful life events and severity of depression

Gil Zalsman, Yung Yu Huang, Maria A. Oquendo, Ainsley K. Burke, Xian Zhang Hu, David A. Brent, Steven P. Ellis, David Goldman, J. John Mann

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: The lower expressing allele of the serotonin transporter gene 5′ promoter region (5-HTTLPR) polymorphism is reported to be associated with susceptibility to depression and suicidality in response to stressful life events. The authors examined the relationship of a triallelic 5-HTTLPR polymorphism to stressful life events, severity of major depression, and suicidality. Method: Mood disorder subjects (N = 191) and healthy volunteers (N=125), all Caucasian subjects of European origin, were genotyped for the triallelic 5-HTT-LPR polymorphism (higher expressing allele: LA; lower expressing alleles: LG, S). All subjects underwent structured clinical interviews to determine DSM-IV diagnoses, ratings of psychopathology, stressful life events, developmental history, and suicidal behavior. CSF 5-HIAA was assayed in a subgroup of subjects. Results: Lower expressing alleles independently predicted greater depression severity and predicted greater severity of major depression with moderate to severe life events compared with the higher expressing LA allele. No associations with suicidal behavior and CSF 5-HIAA were found. Conclusions: Lower expressing transporter alleles, directly and by increasing the impact of stressful life events on severity, explain 31% of the variance in major depression severity. The biological phenotype responsible for these effects remains to be elucidated.

Original languageEnglish
Pages (from-to)1588-1593
Number of pages6
JournalAmerican Journal of Psychiatry
Volume163
Issue number9
DOIs
StatePublished - Sep 2006

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