Gene by Environment Research to Prevent Externalizing Problem Behavior: Ethical Questions Raised from a Public Healthcare Perspective

Chhangur, Rabia R.; Weeland, Joyce; Matthys, Walter; Overbeek, Geertjan

doi:10.1093/phe/phv024

Cited by 5 publications

(6 citation statements)

References 52 publications

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“…With the current state of knowledge, genetic screenings are likely to provide minimal gain in the effectiveness of interventions with potential costs. For example, genetic screening that connects a genetic disposition to externalizing behavior and substance use could lead to stigmatization and discrimination (Chhangur, Weeland, Matthys, & Overbeek, in press). …”

Section: Resultsmentioning

confidence: 99%

Temperament and externalizing behavior as mediators of genetic risk on adolescent substance use.

Trucco

Hicks

Villafuerte

et al. 2016

Journal of Abnormal Psychology

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Understanding how specific genes contribute to risk for addiction remains challenging. This study tests whether childhood temperament and externalizing behavior in early adolescence account for a portion of the association between specific genetic variants and substance use problems in late adolescence. The sample consisted of 487 adolescents from the Michigan Longitudinal Study, a high-risk sample (70.2% male, 81.7% European American ancestry). Polymorphisms across serotonergic (SLC6A4, 5-HTTLPR), dopaminergic (DRD4, u-VNTR), noradrenergic (SLC6A2, rs36021), and GABAergic (GABRA2, rs279858; GABRA6, rs3811995) genes were examined given prior support for associations with temperament, externalizing behavior, and substance use problems. The temperament traits behavioral control and resiliency were assessed using interviewer ratings (ages 9-11), and externalizing behavior (ages 12-14) was assessed using teacher ratings. Self-reported substance use outcomes (ages 15-17) included maximum alcoholic beverages consumed in 24 hours, and frequency of past year cigarette and marijuana use. Behavioral control, resiliency, and externalizing behavior accounted for the associations between polymorphisms in noradrenergic and GABAergic genes and substance use in late adolescence. Individual differences in emotional coping and behavioral regulation represent non-specific neurobiological underpinnings for an externalizing pathway to addiction.

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Section: Resultsmentioning

confidence: 99%

Temperament and externalizing behavior as mediators of genetic risk on adolescent substance use.

Trucco

Hicks

Villafuerte

et al. 2016

Journal of Abnormal Psychology

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“…Quite conceivably it could have something to do with their own genetic makeup and therefore their dopaminergic plasticity. Unfortunately, this critical issue could not be addressed herein because genetic data on parents were not available (see Chhangur et al., ).…”

Section: Discussionmentioning

confidence: 99%

“…As such, G × I (Gene × Intervention) research has several advantages (Belsky & Van IJzendoorn, ; Van IJzendoorn & Bakermans‐Kranenburg, ). First, it eliminates possible Gene × Environment correlations ( r GE) that plague interpretation of virtually all G × E work (Bakermans‐Kranenburg & Van IJzendoorn, ; Chhangur, Weeland, Matthys, & Overbeek, ). Second, G × I research provides a means for establishing differential susceptibility due to its focus on environmental enrichment.…”

Section: Parenting and Externalizing Behaviormentioning

confidence: 99%

Genetic Moderation of Intervention Efficacy: Dopaminergic Genes, The Incredible Years, and Externalizing Behavior in Children

et al. 2016

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This study investigated whether children scoring higher on a polygenic plasticity index based on five dopaminergic genes (DRD4, DRD2, DAT1, MAOA, and COMT) benefited the most from the Incredible Years (IY) parent program. Data were used from a randomized controlled trial including 341 Dutch families with 4- to 8-year-old children (55.7% boys) showing moderate to high levels of problem behavior. IY proved to be most effective in decreasing parent-reported (but not observed) externalizing behavior in boys (but not girls) carrying more rather than fewer dopaminergic plasticity alleles; this Gene × Intervention effect was most pronounced in the case of boys whose parents' manifested the most positive change in parenting in response to the intervention. These results proved robust across a variety of sampling specifications (e.g., intention to treat, ethnicity).

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“…Yet, given the current state of knowledge regarding the genetic architecture underlying adolescent behavior problems, genetic screenings are likely to provide minimal gain in the effectiveness of interventions with possible costs. For example, genetic screenings that connect a genetic disposition to externalizing behavior could lead to stigmatization and discrimination (Chhangur, Weeland, Matthys, & Overbeek, ). Although these proposed approaches may be especially beneficial to youth carrying the minor GABRA2 allele, these findings should be replicated with larger and more diverse samples before firm recommendations for individualized treatment based on genetic makeup can be offered.…”

Section: Discussionmentioning

confidence: 99%

Pathways to Youth Behavior: The Role of Genetic, Neural, and Behavioral Markers

Trucco

Cope

Burmeister

et al. 2018

J of Research on Adolesc

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Neural and temperamental mechanisms through which a genetic risk marker in the γ-amino butyric acid α2 receptor subunit (GABRA2) impacts adolescent functioning were investigated. Participants (N = 80; 29 female) completed an emotional word task during functional magnetic resonance imaging. Behavioral control, negative emotionality, and resiliency temperament constructs were assessed. Externalizing and internalizing problems were the outcomes. Those with the GABRA2 minor allele had reduced activation to positive words in the angular gyrus, middle temporal gyrus, and cerebellum, and to negative words in frontal, parietal, and occipital cortices. Reduced activation in the angular gyrus predicted greater negative emotionality and, in turn, elevated externalizing problems. Reduced activation in the inferior parietal cortex predicted greater resiliency and, in turn, low externalizing problems.

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Gene by Environment Research to Prevent Externalizing Problem Behavior: Ethical Questions Raised from a Public Healthcare Perspective

Cited by 5 publications

References 52 publications

Temperament and externalizing behavior as mediators of genetic risk on adolescent substance use.

Temperament and externalizing behavior as mediators of genetic risk on adolescent substance use.

Genetic Moderation of Intervention Efficacy: Dopaminergic Genes, The Incredible Years, and Externalizing Behavior in Children

Pathways to Youth Behavior: The Role of Genetic, Neural, and Behavioral Markers

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