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5-HTTLPR as a potential moderator of the effects of adverse childhood experiences on risk of antisocial personality disorder

Douglas, Karaa; Chan, Gracea; Gelernter, Joelb,c,d; Arias, Albert J.a; Anton, Raymond F.e; Poling, Jamesb; Farrer, Lindsayf; Kranzler, Henry R.a

doi: 10.1097/YPG.0b013e3283457c15
Original Articles

Introduction Antisocial personality disorder (ASPD) frequently co-occurs with substance dependence (SD). A functional polymorphism (5-HTTLPR) in the serotonin transporter gene has been widely studied as a risk factor for a variety of psychopathologic conditions including aggressive/violent behavior. Childhood abuse is an important predictor of ASPD. We examined 5-HTTLPR genotype and adverse childhood events (ACEs) as risk factors for ASPD in a SD sample.

Materials and methods Study participants [602 European–Americans (EAs) and 779 African–Americans (AAs)] were interviewed to obtain lifetime diagnoses of ASPD and SD and information on ACEs. Triallelic genotypes for 5-HTTLPR were obtained using standard methods. We used logistic generalized estimating equations regression to examine ACEs and 5-HTTLPR genotype and their interaction as predictors of ASPD, separately by population group.

Results There were 203 (14.7%) participants diagnosed with ASPD. The frequency of the low-activity 5-HTTLPR S′ allele did not differ by ASPD diagnosis, and there was no overall 5-HTTLPR×ACE interaction. However, among European–Americans, male sex (odds ratio=3.36; P<0.001) and ACE history (odds ratio=1.47; P=0.002) were significant predictors of ASPD. Among AAs, there was a significant interaction of sex×5-HTTLPR genotype×ACEs (χ 2=13.92, P<0.001). Among AA men, each additional ACE significantly increased the odds of ASPD irrespective of genotype, whereas among AA women, the effect of ACEs on ASPD was significant only among S′ homozygotes. However, these results are limited by the small sample size in each subgroup, (particularly AA women with S′S′ genotype; N=7) and require replication.

Conclusions Childhood maltreatment contributes to the risk of ASPD, an effect for which there is preliminary evidence of moderation by 5-HTTLPR genotype in AA women.

aDepartment of Psychiatry, University of Connecticut School of Medicine, Farmington

bVA CT Healthcare Center, West Haven

cDepartments of Psychiatry

dGenetics and Neurobiology, Yale University, New Haven, Connecticut

eDepartment of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina

fDepartments of Medicine, Neurology, Genetics and Genomics, Epidemiology, and Biostatistics, Boston University Schools of Medicine and Public Health, Boston, Massachusetts, USA

Correspondence to Henry R. Kranzler, MD, Department of Psychiatry, Treatment Research Center, University of Pennsylvania, 3900 Chestnut Street, Philadelphia, PA 19104, USA Tel: +1 215 222 3200 x137; fax: +1 215 386 6770; e-mail:

Received May 20, 2010

Accepted December 22, 2010

© 2011 Lippincott Williams & Wilkins, Inc.