Relationships between wellbeing polygenic scores, brain structure, and psychopathology in children

Abstract Wellbeing is shaped by an interplay of genetic and environmental factors and is associated with both health and functioning. It remains unclear whether genetic influences on wellbeing are linked to brain structure and, in turn, early-life psychopathology. Here, we investigated associations between wellbeing polygenic scores (PGS), magnetic resonance imaging (MRI)-derived measures of brain structure, and parent-reported measures of child psychopathology in a large cross-sectional sample of children from the Adolescent Brain Cognitive Development (ABCD) Study (n = 8844; 8.9-11.0 years old). Preregistered analyses revealed no significant associations between wellbeing PGS and regional cortical thickness or subcortical volumes and only a small negative association with surface area of the parahippocampal cortex (β = −0.03, p=.002), while an exploratory analysis identified a small positive association with intracranial volume (ICV; β = 0.04, p<.001). Preregistered analyses showed small negative associations between wellbeing PGS and general psychopathology (β = −0.09, p<.001) and both internalizing (β = - 0.09, p<.001) and externalizing problems (β = −0.07, p<.001). ICV partially mediated the relationships between wellbeing PGS and psychopathology, accounting for 1.3-3.3% of these relationships. The findings suggest that while wellbeing PGS have limited associations with regional brain structure in children, they exhibit small protective effects against psychopathology. Highlights Wellbeing PGS show limited associations with brain structure in children. Negative association found between wellbeing PGS and parahippocampal surface area. Positive association found between wellbeing PGS and intracranial volume. Wellbeing PGS linked to lower levels of parent-reported child psychopathology. Intracranial volume partially mediate wellbeing PGS-psychopathology associations.