Family environment interacts with CRHR1 rs17689918 to predict mental health and behavioral outcomes

Background: Corticotrophin-releasing hormone receptor-1 gene (CRHR1) variants have been implicated in mental health. However, little is known of the effects of CRHR1 on long-term mental health and behavior in presence of environmental stressors. We assess the effects of CRHR1 variant (rs17689918)-by-environment interactions on emotionality and behavioral traits, including anxiety, depression, aggression and antisocial behaviors. We also determine effects of rs17689918-by-environment-by-sex interactions on the above-mentioned outcomes. Methods: Genotypic assessments were carried out in 564 children (mean age 10 years, 52.5% females) from the ongoing longitudinal Estonian Children Personality Behaviour and Health Study (ECPBHS). Information on stressful life events and family relationships were available at baseline and information on behavioral and mental health outcomes (self- and parent-reports) were available at follow-up ages of 18 and 25 years. ANOVAs were used to determine associations of two-way CRHR1-by-environment and three-way CRHR1-by-sex-by-environment interactions on behavioral and mental health outcomes. Results: Two-way CRHR1 interaction effects showed associations between low familial warmth and hostility in individuals with the GG genotype. Associations of low familial warmth with aggression, of higher number of stressful life events with aggression, and of stressful live events with anxious-depressive symptoms were noted in male A-allele carriers and female GG homozygotes. Conclusion: CRHR1-by-familial environment interactions influence both outwardly-directed aggression as well as mood and anxiety disorder symptoms in a sex-specific manner. The type of environmental stressor can also influence effects of CRHR1 on behavioral and mental health outcomes.