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Examining gene-environment interactions in comorbid depressive and disruptive behavior disorders using a Bayesian approach.

ABSTRACT: The objective of this study was to apply a Bayesian statistical analytic approach that minimizes multiple testing problems to explore the combined effects of chronic low familial support and variants in 12 candidate genes on risk for a common and debilitating childhood mental health condition.Bayesian mixture modeling was used to examine gene by environment interactions among genetic variants and environmental factors (family support) associated in previous studies with the occurrence of comorbid depression and disruptive behavior disorders youth, using a sample of 255 children.One main effect, variants in the oxytocin receptor (OXTR, rs53576) was associated with increased risk for comorbid disorders. Two significant gene × environment and one signification gene × gene interactions emerged. Variants in the nicotinic acetylcholine receptor ?5 subunit (CHRNA5, rs16969968) and in the glucocorticoid receptor chaperone protein FK506 binding protein 5 (FKBP5, rs4713902) interacted with chronic low family support in association with child mental health status. One gene × gene interaction, 5-HTTLPR variant of the serotonin transporter (SERT/SLC6A4) in combination with ? opioid receptor (OPRM1, rs1799971) was associated with comorbid depression and conduct problems.Results indicate that Bayesian modeling is a feasible strategy for conducting behavioral genetics research. This approach, combined with an optimized genetic selection strategy (Vrieze et al., 2012), revealed genetic variants involved in stress regulation (FKBP5, SERT × OPMR), social bonding (OXTR), and nicotine responsivity (CHRNA5) in predicting comorbid status.

SUBMITTER: Adrian M

PROVIDER: S-EPMC4522042 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Examining gene-environment interactions in comorbid depressive and disruptive behavior disorders using a Bayesian approach.

Adrian Molly M Kiff Cara C Glazner Chris C Kohen Ruth R Tracy Julia Helen JH Zhou Chuan C McCauley Elizabeth E Vander Stoep Ann A

Journal of psychiatric research 20150616

<h4>Objective</h4>The objective of this study was to apply a Bayesian statistical analytic approach that minimizes multiple testing problems to explore the combined effects of chronic low familial support and variants in 12 candidate genes on risk for a common and debilitating childhood mental health condition.<h4>Method</h4>Bayesian mixture modeling was used to examine gene by environment interactions among genetic variants and environmental factors (family support) associated in previous studi ...[more]

PMID: 26228411

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Project description:ObjectiveYouths with disruptive behavior disorders (DBD) (conduct disorder and oppositional defiant disorder) have an elevated risk for maladaptive reactive aggression. Theory suggests that this is due to an elevated sensitivity of basic threat circuitry implicated in retaliation (amygdala/periaqueductal gray) in youths with DBD and low levels of callous-unemotional traits and dysfunctional regulatory activity in the ventromedial prefrontal cortex in youths with DBD irrespective of callous-unemotional traits.MethodA total of 56 youths 10-18 years of age (23 of them female) participated in the study: 30 youths with DBD, divided by median split into groups with high and low levels of callous-unemotional traits, and 26 healthy youths. All participants completed an ultimatum game task during functional MRI.ResultsRelative to the other groups, youths with DBD and low levels of callous-unemotional traits showed greater increases in activation of basic threat circuitry when punishing others and dysfunctional down-regulation of the ventromedial prefrontal cortex during retaliation. Relative to healthy youths, all youths with DBD showed reduced amygdala-ventromedial prefrontal cortex connectivity during high provocation. Ventromedial prefrontal cortex responsiveness and ventromedial prefrontal cortex-amygdala connectivity were related to patients' retaliatory propensity (behavioral responses during the task) and parent-reported reactive aggression.ConclusionsThese data suggest differences in the underlying neurobiology of maladaptive reactive aggression in youths with DBD who have relatively low levels of callous-unemotional traits. Youths with DBD and low callous-unemotional traits alone showed significantly greater threat responses during retaliation relative to comparison subjects. These data also suggest that ventromedial prefrontal cortex-amygdala connectivity is critical for regulating retaliation/reactive aggression and, when dysfunctional, contributes to reactive aggression, independent of level of callous-unemotional traits.

Dataset Information

Examining gene-environment interactions in comorbid depressive and disruptive behavior disorders using a Bayesian approach.

Publications

Examining gene-environment interactions in comorbid depressive and disruptive behavior disorders using a Bayesian approach.

Similar Datasets

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