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Neurobiological, familial and genetic risk factors for dimensional psychopathology in the Adolescent Brain Cognitive Development study

Molecular Psychiatry volume 27, pages 2731–2741 (2022)Cite this article

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Abstract

Background

Adolescence is a key period for brain development and the emergence of psychopathology. The Adolescent Brain Cognitive Development (ABCD) study was created to study the biopsychosocial factors underlying healthy and pathological brain development during this period, and comprises the world’s largest youth cohort with neuroimaging, family history and genetic data.

Methods

We examined 9856 unrelated 9-to-10-year-old participants in the ABCD study drawn from 21 sites across the United States, of which 7662 had multimodal magnetic resonance imaging scans passing quality control, and 4447 were non-Hispanic white and used for polygenic risk score analyses. Using data available at baseline, we associated eight ‘syndrome scale scores’ from the Child Behavior Checklist—summarizing anxious/depressed symptoms, withdrawn/depressed symptoms, somatic complaints, social problems, thought problems, attention problems, rule-breaking behavior, and aggressive behavior—with resting-state functional and structural brain magnetic resonance imaging measures; eight indicators of family history of psychopathology; and polygenic risk scores for major depression, bipolar disorder, schizophrenia, attention deficit hyperactivity disorder (ADHD) and anorexia nervosa. As a sensitivity analysis, we excluded participants with clinically significant (>97th percentile) or borderline (93rd–97th percentile) scores for each dimension.

Results

Most Child Behavior Checklist dimensions were associated with reduced functional connectivity within one or more of four large-scale brain networks—default mode, cingulo-parietal, dorsal attention, and retrosplenial-temporal. Several dimensions were also associated with increased functional connectivity between the default mode, dorsal attention, ventral attention and cingulo-opercular networks. Conversely, almost no global or regional brain structural measures were associated with any of the dimensions. Every family history indicator was associated with every dimension. Major depression polygenic risk was associated with six of the eight dimensions, whereas ADHD polygenic risk was exclusively associated with attention problems and externalizing behavior (rule-breaking and aggressive behavior). Bipolar disorder, schizophrenia and anorexia nervosa polygenic risk were not associated with any of the dimensions. Many associations remained statistically significant even after excluding participants with clinically significant or borderline psychopathology, suggesting that the same risk factors that contribute to clinically significant psychopathology also contribute to continuous variation within the clinically normal range.

Conclusions

This study codifies neurobiological, familial and genetic risk factors for dimensional psychopathology across a population-scale cohort of community-dwelling preadolescents. Future efforts are needed to understand how these multiple modalities of risk intersect to influence trajectories of psychopathology into late adolescence and adulthood.

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Fig. 1: Distributions of Child Behavior Checklist dimensions.
Fig. 2: Cohort inclusion criteria.

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Acknowledgements

MW and SJT acknowledge support from the Kavli Foundation, Krembil Foundation, CAMH Discovery Fund, the McLaughlin Foundation, NSERC (RGPIN-2020-05834 and DGECR-2020-00048) and CIHR (NGN-171423).

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Authors and Affiliations

  1. Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada

    Michael Wainberg, Grace R. Jacobs, Aristotle N. Voineskos & Shreejoy J. Tripathy

  2. Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada

    Grace R. Jacobs, Aristotle N. Voineskos & Shreejoy J. Tripathy

  3. Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada

    Aristotle N. Voineskos & Shreejoy J. Tripathy

  4. Department of Physiology, University of Toronto, Toronto, Ontario, Canada

    Shreejoy J. Tripathy

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  1. Michael Wainberg
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MW and SJT designed the study; MW performed analyses; SJT supervised the study; MW wrote the manuscript with key input from GRJ, AV, and SJT.

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Correspondence to Shreejoy J. Tripathy.

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Wainberg, M., Jacobs, G.R., Voineskos, A.N. et al. Neurobiological, familial and genetic risk factors for dimensional psychopathology in the Adolescent Brain Cognitive Development study. Mol Psychiatry 27, 2731–2741 (2022). https://doi.org/10.1038/s41380-022-01522-w

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