Assessing a multivariate model of brain-mediated genetic influences on disordered eating in the ABCD cohort

Eating disorders often emerge during adolescence, and affected individuals frequently demonstrate high rates of psychiatric comorbidity, particularly with depressive and anxiety disorders. Although risk for eating disorders reflects both genetic and neurobiological factors, knowledge of how genetic risk for eating disorders relates to neurobiology and psychiatric symptoms during critical developmental periods remains limited. Here we simultaneously estimated associations between genetic risk, brain structure, and eating-disorder-related psychopathology symptoms in over 4,900 adolescents of European ancestry from the ABCD study (mean age (s.d.) = 9.94 (0.62) years). Polygenic scores for anorexia nervosa (AN PGS) and body mass index (BMI PGS) were related to three morphometric brain features—cortical thickness, surface area, and subcortical gray matter volume—and to latent psychopathology factors using structural equation modeling. We identified a three-factor structure of eating-disorder-related psychopathology symptoms: eating, distress, and fear factors. Increased BMI PGS were uniquely associated with greater eating factor scores. Moreover, greater BMI PGS predicted widespread increases in cortical thickness and reductions in surface area while AN PGS were related to reduced caudate volume. Altered default mode and visual network thickness was associated with greater eating factor scores, whereas distress and fear factor scores reflected a shared reduction in somatomotor network thickness. Our novel findings indicate that greater genetic risk for high BMI and altered cortical thickness of canonical brain networks underpin eating disorder symptomatology in early adolescence. As neurobiological factors appear to shape disordered eating earlier in development than previously thought, these results underscore the need for early detection and intervention efforts for eating disorders.