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Interactions Between Genetic, Prenatal Substance Use, Puberty, and Parenting are Less Important for Understanding Adolescents’ Internalizing, Externalizing, and Substance Use than Developmental Cascades in Multifactorial Models

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Abstract

This study tested interactions among puberty-related genetic risk, prenatal substance use, harsh discipline, and pubertal timing for the severity and directionality (i.e., differentiation) of externalizing and internalizing problems and adolescent substance use. This is a companion paper to Marceau et al. (2021) which examined the same influences in developmental cascade models. Data were from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort (n = 4504 White boys, n = 4287 White girls assessed from the prenatal period through 18.5 years). We hypothesized generally that later predictors would strengthen the influence of puberty-related genetic risk, prenatal substance use exposure, and pubertal risk on psychopathology and substance use (two-way interactions), and that later predictors would strengthen the interactions of earlier influences on psychopathology and substance use (three-way interactions). Interactions were sparse. Although all fourteen interactions showed that later influences can exacerbate or trigger the effects of earlier ones, they often were not in the expected direction. The most robust moderator was parental discipline, and differing and synergistic effects of biological and socially-relevant aspects of puberty were found. In all, the influences examined here operate more robustly in developmental cascades than in interaction with each other for the development of psychopathology and transitions to substance use.

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Data Availability

Data for the current study is available from the ALSPAC study: http://www.bristol.ac.uk/alspac/researchers/access/. Derived variables and associated code for variables created in this study are returned to the ALSPAC executive team, and are available/distributed by ALSPAC. Data analytic scripts or additional details are freely available upon author request.

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Acknowledgements

We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses.

Funding

The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors, who will serve as guarantors for the contents of this paper. A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). GWAS data was generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. This research was specifically funded by the National Institute on Drug Abuse (K01 DA039288, Marceau).

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Authors and Affiliations

  1. Purdue University, 225 Hanley Hall, 1202 Mitch Daniels Blvd, West Lafayette, IN, 47907, USA

    Kristine Marceau, Amy M. Loviska & Valerie S. Knopik

  2. Department of Biostatistics, University of Michigan, 1415 Washington Heights, Ann Arbor, MI, 48109, USA

    Gregor Horvath

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  1. Kristine Marceau
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  2. Amy M. Loviska
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  3. Gregor Horvath
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  4. Valerie S. Knopik
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Contributions

KM conceived of the study, analyzed the data, and drafted the manuscript. GH and AL were instrumental in construction of key study variables. VK was instrumental in conceptualizing the study. All authors edited the manuscript and approved of the final manuscript prior to submission.

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Correspondence to Kristine Marceau.

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Conflict of interest

Kristine Marceau, Amy M. Loviska, Gregor Horvath and Valerie S. Knopik declare that they have no conflict of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Ethical approval for the study was obtained from the ALSPAC Ethics and Law Committee and the Local Research Ethics Committees. Ethical approval for the present data analysis was also obtained from the Purdue University IRB.

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Informed consent for the use of data collected via questionnaires and clinics was obtained from participants following the recommendations of the ALSPAC Ethics and Law Committee at the time.

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Marceau, K., Loviska, A., Horvath, G. et al. Interactions Between Genetic, Prenatal Substance Use, Puberty, and Parenting are Less Important for Understanding Adolescents’ Internalizing, Externalizing, and Substance Use than Developmental Cascades in Multifactorial Models. Behav Genet 54, 181–195 (2024). https://doi.org/10.1007/s10519-023-10164-9

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