Interactive Effect of Stressful Life Events and the Serotonin Transporter 5-HTTLPR Genotype on Posttraumatic Stress Disorder Diagnosis in 2 Independent Populations
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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 x 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.
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Xie et al. (2009) found an interaction between childhood experiences of crime and abuse and FKBP5 genotype in predicting PTSD in African Americans, but not European Americans.
“there was an interaction between childhood experiences of crime and abuse and FKBP5 genotype in predicting PTSD in African Americans, but not European Americans.”
From Gene–environment interactions: early life stress and risk for depressive and anxiety disorders (2011) · cites this paper as Xie et al. (2009)
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- Authors
- Xie, P., Kranzler, H. R., Poling, J., Stein, M. B., Anton, R. F., Brady, K., Weiss, R. D., Farrer, L., & Gelernter, J.
- Affiliations
- Yale University (US)
- Boston University (US)
- ORCID
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2009-11-01
- Volume
- 66
- Issue
- 11
- Pages
- 1201
- ISSN
- 0003-990X (ISSN-L)
- PMC
- PMC2867334
- OpenAlex
- W2150523152
- Cited by
- 264
- References
- 49
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 5 · 2023: 17 · 2022: 4 · 2021: 1 · 2020: 5 · 2019: 13 · 2018: 7 · 2017: 13 · 2016: 23 · 2015: 28 · 2014: 21 · 2013: 35 · 2012: 30
- FWCI
- 27.65
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (R01 AA 11330, R01AA011330, K24AA013736)
- National Institute on Drug Abuse (R01-DA12690, R01 DA 12849, K24 DA15105, K24DA022288, 24DA022288, R01DA012690, K24DA015105, R01DA012849)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Keywords
- post-traumatic stress disorder, 5-HTTLPR, serotonin transporter gene, gene-environment interaction, childhood adversity, traumatic events, life events, serotonin transporter, PTSD etiology, African Americans, European Americans, substance dependence
- MeSH terms
- Adolescent, Adult, Aged, Black or African American, Child, Child Abuse, Cross-Sectional Studies, Female, Genotype, Homozygote, Humans, Life Change Events, Male, Middle Aged, Polymorphism, Genetic, Psychiatric Status Rating Scales, Risk Factors, Social Environment, Stress Disorders, Post-Traumatic, Substance-Related Disorders, Genetic Predisposition to Disease, Diagnostic and Statistical Manual of Mental Disorders, White People, Serotonin Plasma Membrane Transport Proteins
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