Motivation and Cognitive Abilities as Mediators Between Polygenic Scores and Psychopathology in Children.

Fundamental questions in biological psychiatry concern the mechanisms that mediate between genetic liability and psychiatric symptoms. Genetic liability for many common psychiatric disorders often confers transdiagnostic risk to develop a wide variety of psychopathological symptoms through yet unknown pathways. This study examined the psychological and cognitive pathways that might mediate the relationship between genetic liability (indexed by polygenic scores; PS) and broad psychopathology (indexed by p factor and its underlying dimensions). First, which of the common psychiatric PSs (major depressive disorder [MDD], attention-deficit/hyperactivity disorder [ADHD], anxiety, bipolar disorder, schizophrenia, autism) that were associated with p factor were identified. Then focused was shifted to 3 pathways: punishment sensitivity (reflected by behavioral inhibition system), reward sensitivity (reflected by behavioral activation system), and cognitive abilities (reflected by g factor based on 10 neurocognitive tasks). We applied structural equation modeling on the Adolescent Brain Cognitive Development (ABCD) Study dataset (n = 4,814; 2,263 girls; 9-10 years old). MDD and ADHD PSs were associated with p factor. The association between MDD PS and psychopathology was partially mediated by punishment sensitivity and cognitive abilities (proportion mediated = 22.35%). Conversely, the influence of ADHD PS on psychopathology was partially mediated by reward sensitivity and cognitive abilities (proportion mediated = 30.04%). The mediating role of punishment sensitivity was specific to emotional/internalizing. The mediating role of both reward sensitivity and cognitive abilities was specific to behavioral/externalizing and neurodevelopmental dimensions of psychopathology. This study provides a better understanding of how genetic risks for MDD and ADHD confer risks for psychopathology and suggests potential prevention/intervention targets for children at risk.

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