School of Medicine Publications and Presentations
Document Type
Article
Publication Date
3-31-2021
Abstract
Background: Questions remain regarding whether genetic influences on early life psychopathology overlap with cognition and show developmental variation.
Methods: Using data from 9,421 individuals aged 8-21 from the Philadelphia Neurodevelopmental Cohort, factors of psychopathology were generated using a bifactor model of item-level data from a psychiatric interview. Five orthogonal factors were generated: anxious-misery (mood and anxiety), externalizing (attention deficit hyperactivity and conduct disorder), fear (phobias), psychosis-spectrum, and a general factor. Genetic analyses were conducted on a subsample of 4,662 individuals of European American ancestry. A genetic relatedness matrix was used to estimate heritability of these factors, and genetic correlations with executive function, episodic memory, complex reasoning, social cognition, motor speed, and general cognitive ability. Gene × Age analyses determined whether genetic influences on these factors show developmental variation.
Results: Externalizing was heritable (h2 = 0.46, p = 1 × 10-6), but not anxious-misery (h2 = 0.09, p = 0.183), fear (h2 = 0.04, p = 0.337), psychosis-spectrum (h2 = 0.00, p = 0.494), or general psychopathology (h2 = 0.21, p = 0.040). Externalizing showed genetic overlap with face memory (ρg = -0.412, p = 0.004), verbal reasoning (ρg = -0.485, p = 0.001), spatial reasoning (ρg = -0.426, p = 0.010), motor speed (ρg = 0.659, p = 1x10-4), verbal knowledge (ρg = -0.314, p = 0.002), and general cognitive ability (g)(ρg = -0.394, p = 0.002). Gene × Age analyses revealed decreasing genetic variance (γg = -0.146, p = 0.004) and increasing environmental variance (γe = 0.059, p = 0.009) on externalizing.
Conclusions: Cognitive impairment may be a useful endophenotype of externalizing psychopathology and, therefore, help elucidate its pathophysiological underpinnings. Decreasing genetic variance suggests that gene discovery efforts may be more fruitful in children than adolescents or young adults.
Recommended Citation
Mollon J, Knowles EEM, Mathias SR, Rodrigue A, Moore TM, Calkins ME, Gur RC, Peralta JM, Weiner DJ, Robinson EB, Gur RE, Blangero J, Almasy L, Glahn DC (2021). Genetic influences on externalizing psychopathology overlap with cognitive functioning and show developmental variation. European Psychiatry, 64(1), e29, 1–9 https://doi.org/10.1192/j.eurpsy.2021.21
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Publication Title
European Psychiatry
DOI
10.1192/j.eurpsy.2021.21
Academic Level
faculty
Mentor/PI Department
Office of Human Genetics
Comments
© The Author(s), 2021. Published by Cambridge University Press on behalf of the European Psychiatric Association