Effects of genetic risk for depression and household socioeconomic status on emotional behavior and brain development in early adolescence

BACKGROUND: The World Health Organization ranks depression as the leading non-fatal contributor to the global burden of disease. Research shows that early intervention before clinical onset leads to better outcomes. To study depression at this pre-onset stage, risk can be evaluated through depressive prodromal behaviors and associated brain biomarkers. Both environmental and genetic factors independently contribute to depression vulnerability, yet little work has examined how they interact. We therefore examined whether the socioeconomic status (SES) predictor of family income-to-needs ratio (INR) has independent and/or interactive effects with a depression polygenic risk score (D-PRS) on youth behavior and brain structure and function. METHODS: We leveraged the longitudinal ABCD Study®; this work examined 8442 subjects (53% male), 9-10 years-of-age at baseline to 11-12 years-of-age at 2-year follow-up. The prior genetic analysis was conducted in a European-like sample. Therefore, our work first assessed effects in youth with European-like genetic ancestry. Next, to improve generalizability, the same analyses were conducted in not European-like youths. RESULTS: D-PRS was associated with behavior and brain within the European-like youths, with less effect in the not European-like sample. There were moderating effects of INR, with lower INR associating with a lower slope. CONCLUSIONS: Our findings suggest brain-behavior biomarkers associated with SES and D-PRS vary by genetic ancestry; this difference between ancestry groups is likely caused by systemic differences in SES distributions and varying D-PRS predictability from genetic research homogeneity. These outcomes further highlight the importance of equitable and inclusive precision-based research to improve depression early detection and treatment.