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A novel differential susceptibility gene: CHRNA4 and moderation of the effect of maltreatment on child personality.

ABSTRACT: BACKGROUND:The differential susceptibility hypothesis states that some genetic variants that confer risk in adverse environments are beneficial in normal or nurturing environments. The cholinergic system is promising as a source of susceptibility genes because of its involvement in learning and neural plasticity. The cholinergic receptor gene CHRNA4 has been linked to characteristics related to the personality traits Neuroticism and Openness/Intellect. METHODS:The effects of interaction between CHRNA4 genotype and maltreatment status on child personality were examined in a well matched sample of 339 maltreated and 275 non-maltreated children (aged 8-13 years). RESULTS:Variation in CHRNA4 interacted with childhood maltreatment to predict personality in a manner indicating differential susceptibility. The interaction of CHRNA4 and maltreatment status predicted Neuroticism and Openness/Intellect. Maltreated children with the rs1044396 T/T genotype scored highest on Neuroticism and showed no effect of genotype on Openness/Intellect. Non-maltreated children with this genotype scored lowest on Neuroticism and highest on Openness/Intellect. CONCLUSION:Variation in CHRNA4 appears to contribute to personality by affecting degree of developmental sensitivity to both normal and adverse environments.

SUBMITTER: Grazioplene RG

PROVIDER: S-EPMC3608843 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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A novel differential susceptibility gene: CHRNA4 and moderation of the effect of maltreatment on child personality.

Grazioplene Rachael G RG Deyoung Colin G CG Rogosch Fred A FA Cicchetti Dante D

Journal of child psychology and psychiatry, and allied disciplines 20121213 8

<h4>Background</h4>The differential susceptibility hypothesis states that some genetic variants that confer risk in adverse environments are beneficial in normal or nurturing environments. The cholinergic system is promising as a source of susceptibility genes because of its involvement in learning and neural plasticity. The cholinergic receptor gene CHRNA4 has been linked to characteristics related to the personality traits Neuroticism and Openness/Intellect.<h4>Methods</h4>The effects of inter ...[more]

PMID: 23240931

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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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Dataset Information

A novel differential susceptibility gene: CHRNA4 and moderation of the effect of maltreatment on child personality.

Publications

A novel differential susceptibility gene: CHRNA4 and moderation of the effect of maltreatment on child personality.

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