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

ABSTRACT: 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.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.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 (?=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.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.

SUBMITTER: Douglas K

PROVIDER: S-EPMC3119731 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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

Douglas Kara K Chan Grace G Gelernter Joel J Arias Albert J AJ Anton Raymond F RF Poling James J Farrer Lindsay L Kranzler Henry R HR

Psychiatric genetics 20111001 5

<h4>Introduction</h4>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.<h4>Materials and methods</h4>Stud ...[more]

PMID: 21399568

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Project description:BackgroundAdverse childhood experiences (ACEs) are common and linked to negative health outcomes. Previous studies have found associations between ACEs and binge-eating disorder (BED), though they have mainly focused on adults and use cross-sectional data. The objective of this study was to examine the associations between ACEs and BED in a large, national cohort of 9-14-year-old early adolescents in the US.MethodsWe analyzed prospective cohort data from the Adolescent Brain Cognitive Development (ABCD) Study (N = 10,145, 2016-2020). Logistic regression analyses were used to determine the associations between self-reported ACEs and BED based on the Kiddie Schedule for Affective Disorders and Schizophrenia at two-year follow-up, adjusting for sex, race/ethnicity, baseline household income, parental education, site, and baseline binge-eating disorder.ResultsIn the sample, (49% female, 46% racial/ethnic minority), 82.8% of adolescents reported at least one ACE and 1.2% had a diagnosis of BED at two-year follow-up. The mean number of ACEs was higher in those with a diagnosis of BED compared to those without (2.6 ± 0.14 vs 1.7 ± 0.02). The association between number of ACEs and BED in general had a dose-response relationship. One ACE (adjusted odds ratio [aOR] 3.48, 95% confidence interval [CI] 1.11-10.89), two ACEs (aOR 3.88, 95% CI 1.28-11.74), and three or more ACEs (aOR 8.94, 95% CI 3.01-26.54) were all associated with higher odds of BED at two-year follow-up. When stratified by types of ACEs, history of household mental illness (aOR 2.18, 95% 1.31-3.63), household violence (aOR 2.43, 95% CI 1.42-4.15), and criminal household member (aOR 2.14, 95% CI 1.23-3.73) were most associated with BED at two-year follow-up.ConclusionsChildren and adolescents who have experienced ACEs, particularly household challenges, have higher odds of developing BED. Clinicians may consider screening for ACEs and providing trauma-focused care when evaluating patients for BED.

Project description:There is strong evidence that adverse childhood experiences (ACEs) negatively impact mental health. However, the association between ACEs and personality, emotions and affect are poorly understood. Therefore, we examined the association between composite ACE score and ACE type and personality, emotions and positive and negative affect. Three waves of data from the Midlife Development in the United States (MIDUS) study were used. ACE was the primary independent correlate. Covariates included demographic variables and survey wave. Outcome variables included generativity, personality traits (agreeableness, conscientiousness, extraversion, neuroticism, openness, agency), and affect (positive, negative.) Statistical analyses included 3 approaches: 1) treatment of ACE as dichotomous, 2) ordinal composite of ACE score, and 3) three individual ACE type components to assess the association between ACE and psychological constructs. Of 6,323 adults in the sample, 53% were female, and 56% had a past ACE. In the adjusted analyses, dichotomized ACE was significantly associated with neuroticism (β=0.10; 95% CI 0.07, 0.13) and conscientiousness (β=-0.03; 95% CI -0.05, -0.01). All ACE scores were significantly and positively associated with neuroticism and negatively associated with conscientiousness. Abuse was significantly associated with neuroticism (β=0.20; 95% CI 0.16, 0.24), openness (β=0.08; 95% CI 0.05, 0.11), conscientiousness (β=-0.05; 95% CI -0.08, -0.02), and agency (β=0.06; 95% CI 0.02, 0.10). All ACE categories, except financial strain, were significantly associated with affect. ACEs are significantly associated with personality, emotions, and affect, with greater effect seen at higher ACE scores and with ACE abuse type, which helps support the cumulative risk hypothesis and our study hypothesis. There is a need for continued research to understand the mechanistic processes and the directionality of the association between ACEs, emotions, and behaviors to help continue to drive biopsychosocial interventions.

Dataset Information

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

Publications

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

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