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Pathways link environmental and genetic factors with structural brain networks and psychopathology in youth

Neuropsychopharmacology (2023)Cite this article

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Abstract

Adolescence is a period of significant brain development and maturation, and it is a time when many mental health problems first emerge. This study aimed to explore a comprehensive map that describes possible pathways from genetic and environmental risks to structural brain organization and psychopathology in adolescents. We included 32 environmental items on developmental adversity, maternal substance use, parental psychopathology, socioeconomic status (SES), school and family environment; 10 child psychopathological scales; polygenic risk scores (PRS) for 10 psychiatric disorders, total problems, and cognitive ability; and structural brain networks in the Adolescent Brain Cognitive Development study (ABCD, n = 9168). Structural equation modeling found two pathways linking SES, brain, and psychopathology. Lower SES was found to be associated with lower structural connectivity in the posterior default mode network and greater salience structural connectivity, and with more severe psychosis and internalizing in youth (p < 0.001). Prematurity and birth weight were associated with early-developed sensorimotor and subcortical networks (p < 0.001). Increased parental psychopathology, decreased SES and school engagement was related to elevated family conflict, psychosis, and externalizing behaviors in youth (p < 0.001). Increased maternal substance use predicted increased developmental adversity, internalizing, and psychosis (p < 0.001). But, polygenic risks for psychiatric disorders had moderate effects on brain structural connectivity and psychopathology in youth. These findings suggest that a range of genetic and environmental factors can influence brain structural organization and psychopathology during adolescence, and that addressing these risk factors may be important for promoting positive mental health outcomes in young people.

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Fig. 1: Environment-wide associations with brain structural connectivities.
Fig. 2: PRS-wide associations with brain structural connectivities.
Fig. 3: Child psychopathology-wide associations with brain structural connectivities.
Fig. 4: Heatmap among the environmental factors, polygenic risk scores, and child transdiagnostic dimensions of psychopathology.
Fig. 5: Pathways link environmental factors and polygenic risk scores with the brain structural connectivity and transdiagnostic dimensions of psychopathology in youth.

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Funding

Funding

This research is supported by the National Science Foundation (NSF:2010778) and National Research Foundation. Additional funding is provided by the Singapore Ministry of Education (Academic research fund Tier 1) and A*STAR (H22P0M0007). This research was supported by the STI 2030—Major Project (No. 2022ZD0209000) and the A*STAR Computational Resource Centre through the use of its high-performance computing facilities. Data used in the preparation of this article were obtained from the Adolescent Brain Cognitive Development (ABCD) Study (https://abcdstudy.org), held in the NIMH Data Archive [77]. This is a multisite, longitudinal study designed to recruit more than 10,000 children age 9-10 and follow them over 10 years into early adulthood. The ABCD Study is supported by the National Institutes of Health and additional federal partners under awards U01DA041022, U01DA041025, U01DA041028, U01DA041048, U01DA041089, U01DA041093, U01DA041106, U01DA041117, U01DA041120, U01DA041134, U01DA041148, U01DA041156, U01DA041174, U24DA041123, and U24DA041147. A full list of supporters is available at https://abcdstudy.org/federal-partners/. A listing of participating sites and a complete listing of the study investigators can be found at https://abcdstudy.org/study-sites/. ABCD consortium investigators designed and implemented the study and/or provided data but did not necessarily participate in analysis or writing of this report. This manuscript reflects the views of the authors and may not reflect the opinions or views of the NIH or ABCD consortium investigators. The ABCD data repository grows and changes over time. The ABCD data used in this report came from https://doi.org/10.15154/1503209.

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Authors and Affiliations

  1. Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore

    Anqi Qiu & Chaoqiang Liu

  2. The N.1 Institute for Health, National University of Singapore, Singapore, Singapore

    Anqi Qiu

  3. NUS (Suzhou) Research Institute, National University of Singapore, Suzhou, China

    Anqi Qiu

  4. Institute of Data Science, National University of Singapore, Singapore, Singapore

    Anqi Qiu

  5. Department of Health Technology and Informatics, Hong Kong Polytechnic University, Hong Kong, Hong Kong

    Anqi Qiu

  6. Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD, USA

    Anqi Qiu

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AQ designed the study, conducted the analyses, interpreted the findings, and drafted the manuscript. CL made substantial contributions to the DTI analysis. All authors gave their final approval of the version to be published and agreed to be accountable for all aspects of the work.

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Qiu, A., Liu, C. Pathways link environmental and genetic factors with structural brain networks and psychopathology in youth. Neuropsychopharmacol. (2023). https://doi.org/10.1038/s41386-023-01559-7

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