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Hypothesis-driven research for G × E interactions: the relationship between oxytocin, parental divorce during adolescence, and depression in young adulthood.

ABSTRACT: Research in molecular genetics has generally focused on genome-wide association studies (GWAS) and exploratory candidate gene and candidate gene-environment (G × E) studies. In this article it is proposed that hypothesis-driven and biologically informed research provides a complementary approach to GWAS to advance pressing research questions about G × E relations that are of public health relevance. Prior research studies and developmental and evolutionary theory were used to guide hypothesis testing of G × E relationships in this study. The study investigated whether the oxytocin polymorphism, rs53576, moderated the relationship between parental divorce during adolescence and depression symptoms in young adulthood. Oxytocin is a neuropeptide that has been related to the regulation of complex social cognition and behaviors such as empathy, attachment, and nurturance. We hypothesized that the GG polymorphism would be associated with more depressive symptoms following parental divorce, and that this effect would be stronger in females than males. The sample consisted of 340 individuals who participated in a longitudinal study with data used both from adolescence and young adulthood. Findings using prospective follow-up and autoregressive change models supported the hypothesized relationships. Young adult females who had experienced parental divorce during adolescence and had the GG oxytocin genotype reported almost twice as many depressive symptoms relative to young adult females who also experienced parental divorce during adolescence but had the AA or AG genotype. This pattern was not indicated among males. Findings were discussed with regard to how molecular genetic factors in combination with environmental stressors, such parental divorce, framed within a developmental framework may facilitate the future study of G × E relationships in the parental divorce-child adjustment literature and contribute to a prevention science perspective.

SUBMITTER: Windle M

PROVIDER: S-EPMC4561344 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Hypothesis-driven research for G × E interactions: the relationship between oxytocin, parental divorce during adolescence, and depression in young adulthood.

Windle Michael M Mrug Sylvie S

Frontiers in psychology 20150907

Research in molecular genetics has generally focused on genome-wide association studies (GWAS) and exploratory candidate gene and candidate gene-environment (G × E) studies. In this article it is proposed that hypothesis-driven and biologically informed research provides a complementary approach to GWAS to advance pressing research questions about G × E relations that are of public health relevance. Prior research studies and developmental and evolutionary theory were used to guide hypothesis te ...[more]

PMID: 26441708

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Project description:ImportanceLess favorable trajectories of depressive mood from adolescence to early adulthood are associated with current and later psychopathology, impaired educational attainment, and social dysfunction, yet the genetic and environmental risk factors associated with these trajectories are not fully established. Examining what risk factors are associated with different trajectories of depressive mood could help identify the nature of depression symptoms and improve preventive interventions for those at most risk.ObjectiveTo examine the differential associations of genetic and environmental risk factors with trajectories of depression symptoms among individuals observed from ages 10 to 24 years.Design, setting, and participantsIn a longitudinal cohort study established in 1990 and currently ongoing (the Avon Longitudinal Study of Parents and Children [ALSPAC]), growth mixture modeling was used to identify trajectories of depression symptoms in 9394 individuals in the United Kingdom. Associations of different risk factors with these trajectories were then examined. Analysis was conducted between August 2018 and January 2019.Main outcomes and measuresTrajectories were composed from depression symptoms measured using the Short Mood and Feelings Questionnaire at 9 occasions from ages 10 to 24 years. Risk factors included sex, a polygenic risk score taken from a recent genome-wide association study of depression symptoms, maternal postnatal depression, partner cruelty to the offspring's mother when the child was aged 2 to 4 years, childhood anxiety at age 8 years, and being bullied at age 10 years.ResultsData on all risk factors, confounders, and the outcome were available for 3525 individuals, including 1771 (50.2%) who were female. Trajectories were assessed between the mean (SD) age of 10.7 (0.3) years and mean (SD) age of 23.8 (0.5) years. Overall, 5 distinct trajectories of depression symptoms were identified: (1) stable low (2506 individuals [71.1%]), (2) adolescent limited (325 individuals [9.2%]), (3) childhood limited (203 individuals [5.8%]), (4) early-adult onset (393 individuals [11.1%]), and (5) childhood persistent (98 individuals [2.8%]). Of all the associations of risk factors with trajectories, sex (odds ratio [OR], 6.45; 95% CI, 2.89-14.38), the polygenic risk score for depression symptoms (OR, 1.47; 95% CI, 1.10-1.96), and childhood anxiety (OR, 1.30; 95% CI, 1.16-1.45) showed the strongest association with the childhood-persistent trajectory of depression symptoms compared with the stable-low trajectory. Maternal postnatal depression (OR, 2.39; 95% CI, 1.41-4.07) had the strongest association with the early-adult-onset trajectory, while partner cruelty to mother (OR, 2.30; 95% CI, 1.36-3.90) had the strongest association with the adolescent-limited trajectory. Bullying (OR, 8.08; 95% CI, 4.92-13.26) showed the strongest association with the childhood-limited trajectory.Conclusions and relevanceThe least favorable trajectories of depression symptoms (childhood persistent and early-adult onset) were associated with both genetic and environmental risk factors, but the 2 trajectories of limited duration that had resolved by early adulthood (childhood limited and adolescent limited) were not associated with the polygenic risk score or maternal postnatal depression. Bullying was strongly associated with both the childhood-persistent and childhood-limited trajectories, suggesting that this risk factor may have a time-specific effect. These findings suggest that examining genetic and multiple time-specific environmental antecedents could help identify trajectories of varying onset and chronicity.

Dataset Information

Hypothesis-driven research for G × E interactions: the relationship between oxytocin, parental divorce during adolescence, and depression in young adulthood.

Publications

Hypothesis-driven research for G × E interactions: the relationship between oxytocin, parental divorce during adolescence, and depression in young adulthood.

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