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From child maltreatment to emerging adult problem drinking: Identification of a multilevel internalizing pathway among African American youth.

ABSTRACT: The present study tested the role of FKBP5 binding protein 5 (FKBP5) genetic variation in an internalizing pathway from child maltreatment to emerging adult problem drinking among a sample of African American youth (N = 280) followed prospectively from ages 11 to 20. Specifically, whether childhood internalizing symptoms and emerging adult tension reduction alcohol expectancies sequentially mediate the effect of child maltreatment on emerging adult problem drinking and whether FKBP5 moderates these associations were investigated. The results indicate that individuals with at least one copy of the FKBP5 CATT haplotype (minor alleles) are more vulnerable to traversing the hypothesized internalizing pathway of risk than individuals without this genotypic profile. Taken together our findings highlight the importance of FKBP5 genetic variation in the context of early adversity; support the role of two prospective sequential mediators of an internalizing pathway to problematic drinking, namely, childhood internalizing symptoms and emerging adult tension reduction alcohol expectancies; and identify a subgroup of maltreated children most susceptible to progressing along this less common pathway of risk.

SUBMITTER: Handley ED

PROVIDER: S-EPMC5718172 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:A model examining the effects of an increasing number of maltreatment subtypes experienced on antisocial behavior, as mediated by impulsivity and moderated by a polygenic index of dopaminergic genotypes, was investigated. An African American sample of children (N = 1,012, M age = 10.07) with and without maltreatment histories participated. Indicators of aggression, delinquency, and disruptive peer behavior were obtained from peer- and counselor-rated measures to form a latent variable of antisocial behavior; impulsivity was assessed by counselor report. Five genotypes in four dopaminergic genes (dopamine receptors D4, D2, known as DRD4, DRD2; dopamine active transporter 1, known as DAT1; and catechol-O-methyltransferase, known as COMT) conferring heightened environmental sensitivity were combined into one polygenic index. Using structural equation modeling, a first-stage, moderated-mediation model was evaluated. Age and sex were entered as covariates, both as main effects and in interaction with maltreatment and the gene index. The model had excellent fit: ?2 (32, N = 1,012) = 86.51, p < .001; comparative fit index = 0.982, Tucker-Lewis index = 0.977, root mean square error of approximation = 0.041, and standardized root mean square residual = 0.022. The effect of maltreatment subtypes on antisocial behavior was partially mediated by impulsivity (? = 0.173, p < .001), and these relations were moderated by the number of differentiating dopaminergic genotypes. Specifically, a significant Gene × Environment interaction (? = 0.016, p = .013) indicated that the relation between maltreatment and impulsivity was stronger as children evinced more differentiating genotypes, thereby strengthening the mediational effect of impulsivity on antisocial behavior. These findings elucidate the manner by which maltreated children develop early signs of antisocial behavior, and the genetic mechanisms involved in greater vulnerability for maladaptation in impulse control within the context of child maltreatment.

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From child maltreatment to emerging adult problem drinking: Identification of a multilevel internalizing pathway among African American youth.

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