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Motivation and cognitive abilities as mediators between polygenic scores and psychopathology in children

Pat, Narun, Riglin, Lucy, Anney, Richard, Wang, Yue, Barch, Deanna, Thapar, Anita and Stringaris, Argyris 2022. Motivation and cognitive abilities as mediators between polygenic scores and psychopathology in children. Journal of the American Academy of Child and Adolescent Psychiatry 61 (6) , pp. 782-795. 10.1016/j.jaac.2021.08.019
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Objective 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). Method 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). Results 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. Conclusion 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher: Elsevier
ISSN: 0890-8567
Date of First Compliant Deposit: 3 September 2021
Date of Acceptance: 31 August 2021
Last Modified: 09 Jun 2022 17:12

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