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CHRM2, parental monitoring, and adolescent externalizing behavior: evidence for gene-environment interaction.

ABSTRACT: Psychologists, with their long-standing tradition of studying mechanistic processes, can make important contributions to further characterizing the risk associated with genes identified as influencing risk for psychiatric disorders. We report one such effort with respect to CHRM2, which codes for the cholinergic muscarinic 2 receptor and was of interest originally for its association with alcohol dependence. We tested for association between CHRM2 and prospectively measured externalizing behavior in a longitudinal, community-based sample of adolescents, as well as for moderation of this association by parental monitoring. We found evidence for an interaction in which the association between the genotype and externalizing behavior was stronger in environments with lower parental monitoring. There was also suggestion of a crossover effect, in which the genotype associated with the highest levels of externalizing behavior under low parental monitoring had the lowest levels of externalizing behavior at the extreme high end of parental monitoring. The difficulties involved in distinguishing mechanisms of gene-environment interaction are discussed.

SUBMITTER: Dick DM

PROVIDER: S-EPMC3391964 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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CHRM2, parental monitoring, and adolescent externalizing behavior: evidence for gene-environment interaction.

Dick Danielle M DM Meyers Jacquelyn L JL Latendresse Shawn J SJ Creemers Hanneke E HE Lansford Jennifer E JE Pettit Gregory S GS Bates John E JE Dodge Kenneth A KA Budde John J Goate Alison A Buitelaar Jan K JK Ormel Johannes J Verhulst Frank C FC Huizink Anja C AC

Psychological science 20110324 4

Psychologists, with their long-standing tradition of studying mechanistic processes, can make important contributions to further characterizing the risk associated with genes identified as influencing risk for psychiatric disorders. We report one such effort with respect to CHRM2, which codes for the cholinergic muscarinic 2 receptor and was of interest originally for its association with alcohol dependence. We tested for association between CHRM2 and prospectively measured externalizing behavio ...[more]

PMID: 21441226

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Project description:ContextAs we identify genes involved in psychiatric disorders, the next step will be to study how the risk associated with susceptibility genes manifests across development and in conjunction with the environment. We describe analyses aimed at characterizing the pathway of risk associated with GABRA2, a gene previously associated with adult alcohol dependence, in a community sample of children followed longitudinally from childhood through young adulthood.ObjectiveTo test for an association between GABRA2 and trajectories of externalizing behavior from adolescence to young adulthood and for moderation of genetic effects by parental monitoring.DesignData were analyzed from the Child Development Project, with yearly assessments conducted since that time. A saliva sample was collected for DNA at the 2006 follow-up, with a 93% response rate in the target sample. Growth mixture modeling was conducted using Mplus to identify trajectories of externalizing behavior and to test for effects of GABRA2 sequence variants and parental monitoring.SettingNashville and Knoxville, Tennessee, and Bloomington, Indiana.ParticipantsA community-based sample of families enrolled at 3 sites as children entered kindergarten in 1987 and 1988. Analyses for the white subset of the sample (n = 378) are reported here.Main outcome measuresParental monitoring measured at 11 years of age; Child Behavior Checklist youth reports of externalizing behavior at ages 12, 14, 15, 16, 17, 19, 20, 21, and 22 years.ResultsTwo classes of externalizing behavior emerged: a stable high externalizing class and a moderate decreasing externalizing behavior class. The GABRA2 gene was associated with class membership, with subjects who showed persistent elevated trajectories of externalizing behavior more likely to carry the genotype previously associated with increased risk of adult alcohol dependence. A significant interaction with parental monitoring emerged; the association of GABRA2 with externalizing trajectories diminished with high levels of parental monitoring.ConclusionsThese analyses underscore the importance of studying genetic effects across development and of identifying environmental factors that moderate risk.

Project description:Adolescents' reports of parental differential treatment have been linked to increased externalizing behaviors. The current study investigated whether adolescent self-esteem and sibling relationship characteristics (age-spacing and sibling relationship quality) moderated associations between parental differential treatment and later externalizing behavior. Data was gathered at two assessments from 708 sibling pairs (94% White; 51% male; same-gender pairs <4 years apart in age). Older/younger siblings were aged MAssessment1?=?13.5/12.1 and MAssessment2?=?16.2/14.7 years. We found that higher levels of maternal differential treatment predicted greater residualized gains in externalizing behavior among older siblings who were (a) the same age as their sibling or near-to and had low self-esteem or (b) three years older than their sibling and had higher self-esteem. Higher levels of paternal differential treatment predicted greater residual gains in externalizing for older siblings with wider age ranges (regardless of self-esteem), and among older siblings with high levels of self-esteem (regardless of age difference). Surprisingly, maternal differential treatment was protective in one case: for adolescents with low self-esteem who were at least three years older than their siblings, maternal differential treatment predicted reduced externalizing behaviors. Paternal differential treatment was protective for more youth than maternal differential treatment: older siblings with low self-esteem who experienced paternal differential treatment exhibited decreased externalizing behaviors across adolescence, regardless of age difference. The findings highlight the importance of self-esteem and sibling age-spacing as particularly salient contextual influences in older siblings' perceptions of maternal and paternal differential treatment, and that maternal and especially paternal differential treatment does not always serve as a risk factor for externalizing problems.

Project description:ImportancePeer deviance (PD) strongly predicts externalizing psychopathologic conditions but has not been previously assessable in population cohorts. We sought to develop such an index of PD and to clarify its effects on risk of drug abuse (DA).ObjectivesTo examine how strongly PD increases the risk of DA and whether this community-level liability indicator interacts with key DA risk factors at the individual and family levels.Design, setting, and participantsStudies of future DA registration in 1,401,698 Swedish probands born from January 1, 1970, through December 31, 1985, and their adolescent peers in approximately 9200 small community areas. Peer deviance was defined as the proportion of individuals born within 5 years of the proband living in the same small community when the proband was 15 years old who eventually were registered for DA.Main outcomes and measuresDrug abuse recorded in medical, legal, or pharmacy registry records.ResultsPeer deviance was associated with future DA in the proband, with rates of DA in older and male peers more strongly predictive than in younger or female peers. The predictive power of PD was only slightly attenuated by adding measures of community deprivation, collective efficacy, or family socioeconomic status. Probands whose parents were divorced were more sensitive to the pathogenic effects of high PD environments. A robust positive interaction was also seen between genetic risk of DA (indexed by rates of DA in first-, second-, and third-degree relatives) and PD exposure.Conclusions and relevanceWith sufficient data, PD can be measured in populations and strongly predicts DA. In a nationwide sample, risk factors at the level of the individual (genetic vulnerability), family (parental loss), and community (PD) contribute substantially to risk of DA. Individuals at elevated DA risk because of parental divorce or high genetic liability are more sensitive to the pathogenic effects of PD. Although the effect of our PD measure on DA liability cannot be explained by standard measures of community or family risk, we cannot, with available data, discriminate definitively between the effect of true peer effects and other unmeasured risk factors.

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CHRM2, parental monitoring, and adolescent externalizing behavior: evidence for gene-environment interaction.

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CHRM2, parental monitoring, and adolescent externalizing behavior: evidence for gene-environment interaction.

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