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Original Article
November 2009

Interactive Effect of Stressful Life Events and the Serotonin Transporter 5-HTTLPR Genotype on Posttraumatic Stress Disorder Diagnosis in 2 Independent Populations

Author Affiliations

Author Affiliations: Departments of Genetics (Dr Gelernter and Ms Xie) and Psychiatry (Drs Gelernter and Poling), Yale University School of Medicine, New Haven, VA Connecticut Healthcare Center, West Haven (Drs Gelernter and Poling and Ms Xie), and Departments of Psychiatry and Genetics and Developmental Biology, University of Connecticut School of Medicine, Farmington (Dr Kranzler); Departments of Psychiatry and Family and Preventive Medicine, University of California, San Diego, and VA San Diego Healthcare System (Dr Stein); Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston (Drs Anton and Brady); Department of Psychiatry, Harvard Medical School and McLean Hospital, Belmont (Dr Weiss), and Departments of Medicine, Neurology, Genetics and Genomics, and Epidemiology and Biostatistics, Boston University School of Medicine and Public Health, Boston (Dr Farrer), Massachusetts.

Arch Gen Psychiatry. 2009;66(11):1201-1209. doi:10.1001/archgenpsychiatry.2009.153

Context  The 5-HTTLPR polymorphism in the promoter region of the serotonin transporter gene (SLC6A4) has been found to moderate several categories of emotional response after stressful life events. Previous studies generally focused on its effect on depressive symptoms; little is known about its moderation of the development of posttraumatic stress disorder (PTSD).

Objective  To examine the effects of childhood adversity, adult traumatic events, 5-HTTLPR genotypes, and gene × environment interactions on the etiology of PTSD.

Design  A cross-sectional study in which participants in several studies investigating the genetics of substance dependence were also screened for lifetime PTSD. The triallelic system of 5-HTTLPR was genotyped. Logistic regression modeling was used in the analyses.

Setting  General community.

Participants  Five hundred eighty-two European American and 670 African American individuals who reported experiences of childhood adversity, adult traumatic events, or both.

Main Outcome Measure  Diagnosis of PTSD, defined by DSM-IV diagnostic criteria and assessed through the Semi-Structured Assessment for Drug Dependence and Alcoholism interview.

Results  Childhood adversity and adult traumatic events both predicted PTSD. Although the 5-HTTLPR genotype alone did not predict the onset of PTSD, it interacted with adult traumatic events and childhood adversity to increase the risk for PTSD, especially for those with high rates of both types of trauma exposure (European American: odds ratio [OR], 2.86; 95% confidence interval [CI], 1.50-5.45; P = .002; African American: OR, 1.88; 95% CI, 1.04-3.40; P = .04; pooled: OR, 2.31; 95% CI, 1.50-3.56; P < .001).

Conclusions  Participants who had both childhood adversity and adult traumatic events were more likely to develop lifetime PTSD compared with those who experienced either type of adverse event. The risk was increased in individuals with 1 or 2 copies of the S’ (S) allele compared with the L’ (L) homozygotes. Our study provides additional direct evidence that PTSD is influenced by the interactive effect of environmental and genetic factors.