title: 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.
authors.affiliation: Department of Psychiatry, University of Groningen, University Medical Center Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands.
authors.forename: Anna Roos E
authors.initials: ARE
authors.lastname: Zandstra
authors.affiliation: Department of Psychiatry, University of Groningen, University Medical Center Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands.
authors.forename: Johan
authors.initials: J
authors.lastname: Ormel
authors.affiliation: Department of Psychiatry, University of Groningen, University Medical Center Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands.
authors.forename: Pieter J
authors.initials: PJ
authors.lastname: Hoekstra
authors.affiliation: Department of Psychiatry, University of Groningen, University Medical Center Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands. C.Hartman@accare.nl.
authors.forename: Catharina A
authors.initials: CA
authors.lastname: Hartman
mesh_terms: D000293:Adolescent; D000294:Adolescent Behavior / Q000502:physiology*; D019958:Attention Deficit and Disruptive Behavior Disorders / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D002648:Child; D002653:Child Behavior Disorders / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D019955:Conduct Disorder / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D005260:Female; D059647:Gene-Environment Interaction; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009426:Netherlands / Q000453:epidemiology; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D013315:Stress, Psychological / Q000150:complications*
chemical_list: C493599:DRD4 protein, human; D050638:Receptors, Dopamine D4
keywords: Adolescence; Chronic stressors; Dopamine D4 receptor 7-repeat allele (DRD4–7R); Externalizing problems; Psychosocial adversity; Sensitivity to the environment