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Genetic influences on externalizing psychopathology overlap with cognitive functioning and show developmental variation

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 usi...

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Autores principales: Mollon, Josephine, Knowles, Emma E. M., Mathias, Samuel R., Rodrigue, Amanda, Moore, Tyler M., Calkins, Monica E., Gur, Ruben C., Peralta, Juan Manuel, Weiner, Daniel J., Robinson, Elise B., Gur, Raquel E., Blangero, John, Almasy, Laura, Glahn, David C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cambridge University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080212/
https://www.ncbi.nlm.nih.gov/pubmed/33785081
http://dx.doi.org/10.1192/j.eurpsy.2021.21
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author Mollon, Josephine
Knowles, Emma E. M.
Mathias, Samuel R.
Rodrigue, Amanda
Moore, Tyler M.
Calkins, Monica E.
Gur, Ruben C.
Peralta, Juan Manuel
Weiner, Daniel J.
Robinson, Elise B.
Gur, Raquel E.
Blangero, John
Almasy, Laura
Glahn, David C.
author_facet Mollon, Josephine
Knowles, Emma E. M.
Mathias, Samuel R.
Rodrigue, Amanda
Moore, Tyler M.
Calkins, Monica E.
Gur, Ruben C.
Peralta, Juan Manuel
Weiner, Daniel J.
Robinson, Elise B.
Gur, Raquel E.
Blangero, John
Almasy, Laura
Glahn, David C.
author_sort Mollon, Josephine
collection PubMed
description 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 (h(2) = 0.46, p = 1 × 10(−6)), but not anxious-misery (h(2) = 0.09, p = 0.183), fear (h(2) = 0.04, p = 0.337), psychosis-spectrum (h(2) = 0.00, p = 0.494), or general psychopathology (h(2) = 0.21, p = 0.040). Externalizing showed genetic overlap with face memory (ρ(g) = −0.412, p = 0.004), verbal reasoning (ρ(g) = −0.485, p = 0.001), spatial reasoning (ρ(g) = −0.426, p = 0.010), motor speed (ρ(g) = 0.659, p = 1x10(−4)), verbal knowledge (ρ(g) = −0.314, p = 0.002), and general cognitive ability (g)(ρ(g) = −0.394, p = 0.002). Gene × Age analyses revealed decreasing genetic variance (γ(g) = −0.146, p = 0.004) and increasing environmental variance (γ(e) = 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.
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spelling pubmed-80802122021-05-13 Genetic influences on externalizing psychopathology overlap with cognitive functioning and show developmental variation Mollon, Josephine Knowles, Emma E. M. Mathias, Samuel R. Rodrigue, Amanda Moore, Tyler M. Calkins, Monica E. Gur, Ruben C. Peralta, Juan Manuel Weiner, Daniel J. Robinson, Elise B. Gur, Raquel E. Blangero, John Almasy, Laura Glahn, David C. Eur Psychiatry Research Article 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 (h(2) = 0.46, p = 1 × 10(−6)), but not anxious-misery (h(2) = 0.09, p = 0.183), fear (h(2) = 0.04, p = 0.337), psychosis-spectrum (h(2) = 0.00, p = 0.494), or general psychopathology (h(2) = 0.21, p = 0.040). Externalizing showed genetic overlap with face memory (ρ(g) = −0.412, p = 0.004), verbal reasoning (ρ(g) = −0.485, p = 0.001), spatial reasoning (ρ(g) = −0.426, p = 0.010), motor speed (ρ(g) = 0.659, p = 1x10(−4)), verbal knowledge (ρ(g) = −0.314, p = 0.002), and general cognitive ability (g)(ρ(g) = −0.394, p = 0.002). Gene × Age analyses revealed decreasing genetic variance (γ(g) = −0.146, p = 0.004) and increasing environmental variance (γ(e) = 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. Cambridge University Press 2021-03-31 /pmc/articles/PMC8080212/ /pubmed/33785081 http://dx.doi.org/10.1192/j.eurpsy.2021.21 Text en © The Author(s), 2021. Published by Cambridge University Press on behalf of the European Psychiatric Association 2021 https://creativecommons.org/licenses/by/4.0/This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Mollon, Josephine
Knowles, Emma E. M.
Mathias, Samuel R.
Rodrigue, Amanda
Moore, Tyler M.
Calkins, Monica E.
Gur, Ruben C.
Peralta, Juan Manuel
Weiner, Daniel J.
Robinson, Elise B.
Gur, Raquel E.
Blangero, John
Almasy, Laura
Glahn, David C.
Genetic influences on externalizing psychopathology overlap with cognitive functioning and show developmental variation
title Genetic influences on externalizing psychopathology overlap with cognitive functioning and show developmental variation
title_full Genetic influences on externalizing psychopathology overlap with cognitive functioning and show developmental variation
title_fullStr Genetic influences on externalizing psychopathology overlap with cognitive functioning and show developmental variation
title_full_unstemmed Genetic influences on externalizing psychopathology overlap with cognitive functioning and show developmental variation
title_short Genetic influences on externalizing psychopathology overlap with cognitive functioning and show developmental variation
title_sort genetic influences on externalizing psychopathology overlap with cognitive functioning and show developmental variation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080212/
https://www.ncbi.nlm.nih.gov/pubmed/33785081
http://dx.doi.org/10.1192/j.eurpsy.2021.21
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