Evidence map›Paper›PMID 33785081›Full record

ArticleEuropean psychiatry : the journal of the Association of European Psychiatrists2021

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

Josephine Mollon, Emma E M Knowles, Samuel R Mathias, Amanda Rodrigue, Tyler M Moore, Monica E Calkins, Ruben C Gur, Juan Manuel Peralta, Daniel J Weiner, Elise B Robinson and 4 more

Abstract read
In one paragraph

Article in European psychiatry : the journal of the Association of European Psychiatrists, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Josephine MollonDepartment of Psychiatry, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.ORCID 0000-0003-4557-1838
Emma E M KnowlesDepartment of Psychiatry, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Samuel R MathiasDepartment of Psychiatry, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Amanda RodrigueDepartment of Psychiatry, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Tyler M MooreBrain Behavior Laboratory, Department of Psychiatry, Perelman School of Medicine, Penn-CHOP Lifespan Brain Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA.ORCID 0000-0002-1384-0151
Monica E CalkinsBrain Behavior Laboratory, Department of Psychiatry, Perelman School of Medicine, Penn-CHOP Lifespan Brain Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Ruben C GurBrain Behavior Laboratory, Department of Psychiatry, Perelman School of Medicine, Penn-CHOP Lifespan Brain Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Juan Manuel PeraltaSouth Texas Diabetes and Obesity Institute, School of Medicine, University of Texas of the Rio Grande Valley, Brownsville, Texas, USA.
Daniel J WeinerAnalytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.ORCID 0000-0002-3744-6853
Elise B RobinsonAnalytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Raquel E GurBrain Behavior Laboratory, Department of Psychiatry, Perelman School of Medicine, Penn-CHOP Lifespan Brain Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
John BlangeroSouth Texas Diabetes and Obesity Institute, School of Medicine, University of Texas of the Rio Grande Valley, Brownsville, Texas, USA.
Laura AlmasyDepartment of Genetics, Perelman School of Medicine, Penn-CHOP Lifespan Brain Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
David C GlahnDepartment of Psychiatry, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Funding

Genetic Analysis and Manipulation Core (GAEC)P50HD105351 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI SCOTT Loren POMEROY, MUSTAFA SAHIN · 2021 to 2026
$9.4M
SOLAR-Eclipse Computational Tools for Imaging GeneticsR01EB015611 · NIBIB · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI KOCHUNOV, PETER V. · 2012 to 2024
$5.0M
Neurodevelopment: Genes, Environment, and their InteractionsR01MH107248 · NIMH · UNIVERSITY OF TEXAS RIO GRANDE VALLEY · PI ALMASY, LAURA A., BLANGERO, JOHN · 2015 to 2017
$1.3M
NIBIB NIH HHS R01 EB015611NICHD NIH HHS P50 HD105351NIMH NIH HHS R01 MH107248
6 · The paper itself

Abstract

backgroundQuestions remain regarding whether genetic influences on early life psychopathology overlap with cognition and show developmental variation.

methodsUsing 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.

resultsExternalizing 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.

conclusionsCognitive 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.

Indexed as

Cognitive DysfunctionPsychotic DisordersAdolescentChildCognitionExecutive FunctionHumansPsychopathologyYoung AdultCognitiondevelopmentexternalizingGene × Ageheritabilitypleiotropypsychopathology

Identifiers

PMID33785081
PMCPMC8080212

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.