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Adolescent substance use initiation and long-term neurobiological outcomes: insights, challenges and opportunities

Molecular Psychiatry (2024)Cite this article

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Abstract

The increased frequency of risk taking behavior combined with marked neuromaturation has positioned adolescence as a focal point of research into the neural causes and consequences of substance use. However, little work has provided a summary of the links between adolescent initiated substance use and longer-term brain outcomes. Here we review studies exploring the long-term effects of adolescent-initiated substance use with structural and microstructural neuroimaging. A quarter of all studies reviewed conducted repeated neuroimaging assessments. Long-term alcohol use, as well as tobacco use were consistently associated with smaller frontal cortices and altered white matter microstructure. This association was mostly observed in the ACC, insula and subcortical regions in alcohol users, and for the OFC in tobacco users. Long-term cannabis use was mostly related to altered frontal cortices and hippocampal volumes. Interestingly, cannabis users scanned more years after use initiation tended to show smaller measures of these regions, whereas those with fewer years since initiation showed larger measures. Long-term stimulant use tended to show a similar trend as cannabis in terms of years since initiation in measures of the putamen, insula and frontal cortex. Long-term opioid use was mostly associated with smaller subcortical and insular volumes. Of note, null findings were reported in all substance use categories, most often in cannabis use studies. In the context of the large variety in study designs, substance use assessment, methods, and sample characteristics, we provide recommendations on how to interpret these findings, and considerations for future studies.

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Fig. 1: Long-term structural cortical brain outcomes associated with substance use initiated in adolescence: overview of the current literature.
Fig. 2: Long-term structural subcortical brain outcomes associated with substance use initiated in adolescence: overview of the current literature.

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Funding

This work was supported by the Stichting Volksbond Rotterdam (OB & HM), the NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation [grant number 27853] (HM); the Netherlands Organization for Health Research and Development [Aspasia grant No.015.016.056] (HM), the Sophia Foundation (S18-20, RM) and the Erasmus MC Fellowship (RM). The study sponsors had no role in the study design, collection, analysis and interpretation of data, writing of the report, or in the decision to submit the paper for publication.

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Authors and Affiliations

  1. Department of Psychology, Education and Child Studies – Erasmus School of Social and Behavioral Sciences, Erasmus University Rotterdam, Rotterdam, The Netherlands

    Olga D. Boer & Hanan El Marroun

  2. Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC University Medical Center – Sophia Children’s Hospital, Rotterdam, The Netherlands

    Olga D. Boer, Hanan El Marroun & Ryan L. Muetzel

  3. Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, The Netherlands

    Ryan L. Muetzel

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  1. Olga D. Boer
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Olga Boer: Conceptualization, Methodology, Investigation, Data curation, Writing - Original draft, Visualization. Hanan El Marroun: Conceptualization, Data curation, Writing - Original draft, Writing - Review & Editing, Funding acquisition, Supervision. Ryan Muetzel: Conceptualization, Data curation, Writing - Original draft, Writing - Review & Editing, Funding acquisition, Supervision.

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Boer, O.D., El Marroun, H. & Muetzel, R.L. Adolescent substance use initiation and long-term neurobiological outcomes: insights, challenges and opportunities. Mol Psychiatry (2024). https://doi.org/10.1038/s41380-024-02471-2

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