Brain structures mediate the causal effects of socioeconomic status on mental disorders: A multi-stage Mendelian...

The associations between socioeconomic status (SES), brain structural alterations, and mental disorders have been well established, but the causal nature and underlying mechanisms of such associations are elusive.

By performing multi-stage Mendelian randomization analyses of multi-source summary data from genome-wide association studies, we explored the causal associations of 3 SES indicators with 12 mental disorders and 13 types of brain structures, pursued by characterization of the mediating roles of brain structures in accounting for the causal effects of SES on mental disorders.

Lower education attainment (EA), lower average total household income before tax (HIBT) and higher Townsend deprivation index at recruitment (TDI) were causally associated with an increased risk of many mental disorders such as attention deficit hyperactivity disorder, major depressive disorder, schizophrenia and cross-disorder, while higher EA, higher HIBT and lower TDI were causally associated with an increased risk of anorexia nervosa. Concurrently, lower EA and HIBT were causally linked to decreased surface area, cortical volume, folding index, intrinsic curvature and local gyrification index across a widely distributed set of cortical regions. More importantly, these brain structural alterations mediated the causal effects of lower EA and HIBT on the increased risk of attention deficit hyperactivity disorder, schizophrenia and cross-disorder.

Our findings shed light on the neurobiological mechanisms whereby disadvantageous SES contributes to specific mental disorders, which may inform future preventive strategies for promoting resilience in high-risk individuals who are exposed to socioeconomic disadvantage.