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

OBJECTIVE: 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. METHOD: 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. RESULTS: 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 α5 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 µ opioid receptor (OPRM1, rs1799971) was associated with comorbid depression and conduct problems. CONCLUSIONS: 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.

A pilot investigation of the association of genetic polymorphisms regulating corticotrophin-releasing hormone with posttraumatic stress and depressive symptoms in medical-surgical intensive care unit survivors.

PURPOSE: To determine if single nucleotide polymorphisms of the corticotrophin-releasing hormone binding protein (CRHBP, rs10055255) and CRH receptor type 1 (CRHR1, rs1876831) were associated with posttraumatic stress disorder (PTSD) and depressive symptoms following medical-surgical intensive care unit (ICU) hospitalization. MATERIALS AND METHODS: We extracted DNA for genotyping from saliva samples of 93 ICU patients enrolled in a prospective cohort investigation. Follow-up interviews conducted 3 and 12-months post-ICU included assessment of PTSD symptoms with the PTSD Checklist-Civilian Version and depressive symptoms with the Patient Health Questionnaire-9. RESULTS: Homozygosity for the CRHBP rs10055255 T allele was associated with significantly fewer post-ICU PTSD (ß = -10.8, 95% confidence interval [95% CI], -17.7 to -3.9; P = .002) and depressive symptoms (ß = -3.7, 95% CI, -6.7 to -0.7; P = .02). Carrying a CRHR1 rs1876831 C allele was associated with significantly more post-ICU depressive symptoms compared to T/T homozygotes (C/T heterozygtes: ß = 6.9, 95% CI, 1.2-12.6; P = .02; C/C homozygotes: ß = 5.8; 95% CI: 0.2-11.3; P = .04). These associations remained significant after adjustment for age, race, illness severity, and in-ICU steroid exposure. CONCLUSIONS: Despite a small sample size, our findings suggest a potential role for genetic variants of CRHBP and CRHR1 in the development of post-ICU psychiatric morbidity.