Interactions between FKBP5 variation and environmental stressors in adolescent Major Depression

Objective: Major Depression (MD) results from a complex interplay between environmental stressors and biological factors. Previous studies in adults have shown that adverse life events interact with genetic variation in FKBP5, a gene implicated in the stress-response system, to predict depressive symptoms and MD. This is the first study to investigate interactions between FKBP5 variants and a range of environmental stressors in adolescents with a clinical diagnosis of MD. Method: 148 male and female adolescents with MD and 143 typically developing (TD) controls (13-18 years) were included in the present study. For self-reported environmental stressors, subjective severity was assessed to allow a classification of these factors as mild, moderate and severe. Sociodemographic stressors were assessed via parental-report. Results: With a heightened number of sociodemographic, moderate and total number of stressors, participants carrying at least one copy of the FKBP5 CATT haplotype or at least one minor allele of various FKBP5 SNPs had the highest risk for being in the MD group. No genetic main effects were found. Sociodemographic stressors as well as self-reported mild, moderate, and severe stressors were more common in depressed than in TD adolescents. Conclusion: This is the first study to show interactions between genetic variation in FKBP5 and environmental stressors in a sample of clinically depressed adolescents. The current study provides important starting-points for preventive efforts and highlights the need for a fine-grained analysis of different forms and severities of environmental stressors and their interplay with genetic variation for understanding the complex etiology of (youth) MD.