Chronic Stressors and Adolescents’ Externalizing Problems: Genetic Moderation by Dopamine Receptor D4. The TRAILS Study

Abstract

The existing literature does not provide consistent evidence that carriers of the Dopamine D4 Receptor 7-repeat allele are more sensitive to adverse environmental influences, resulting in enhanced externalizing problems, compared to noncarriers. One explanation is that the adverse influences examined in prior studies were not severe, chronic, or distressing enough to reveal individual differences in sensitivity reflected by DRD4–7R. This study examined whether the 7-repeat allele moderated the association between chronic stressors capturing multiple stressful aspects of individuals’ lives and externalizing problems in adolescence. We expected that chronic stressor levels would be associated with externalizing levels only in 7-repeat carriers. Using Linear Mixed Models, we analyzed data from 1621 Dutch adolescents (52.2% boys), obtained in three measurement waves (mean age approximately 11, 13.5, and 16 years) from the TRacking Adolescents’ Individual Lives Survey (TRAILS) population-based birth cohort and the parallel clinic-referred cohort. Across informants, we found that higher levels of chronic stressors were related to higher externalizing levels in 7-repeat carriers but not in noncarriers, as hypothesized. Although previous studies on the 7-repeat allele as a moderator of environmental influences on adolescents’ externalizing problems have not convincingly demonstrated individual differences in sensitivity to adverse environmental influences, our findings suggest that adolescent carriers of the Dopamine D4 Receptor 7-repeat allele are more sensitive to chronic, multi-context stressors than noncarriers.Electronic supplementary materialThe online version of this article (doi:10.1007/s10802-017-0279-4) contains supplementary material, which is available to authorized users.

Longitudinal Links between Adolescent and Peer Conduct Problems and Moderation by a Sensitivity Genetic Index

“…On the other hand, a genomic aggregate approach better reflects sensitivity as a heterogeneous phenotype in that the markers that make up the score capture multiple facets of sensitivity. Related to this point is the finding that DRD4 played a relatively weak role in the relation between peer and adolescent conduct problem behaviors, which reflects the inconsistency in the larger literature with regard to DRD4 moderation of peer influences (Kretschmer et al, 2013; Zandstra et al, 2018) and suggests that DRD4 variation and its often‐hypothesized sensitivity phenotype (reward sensitivity) may be less relevant than 5‐HTTLPR and GABRA2 for differences in sensitivity to peer antisocial behavior as it relates to adolescents’ own antisocial behavior. Although DRD4 variation is linked to environmental sensitivity, broadly defined, the specific form of sensitivity may be less important for the relation presently studied.…”

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