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A genetically informed Registered Report on adverse childhood experiences and mental health

Nature Human Behaviour volume 7, pages 269–290 (2023)Cite this article

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Abstract

Children who experience adversities have an elevated risk of mental health problems. However, the extent to which adverse childhood experiences (ACEs) cause mental health problems remains unclear, as previous associations may partly reflect genetic confounding. In this Registered Report, we used DNA from 11,407 children from the United Kingdom and the United States to investigate gene–environment correlations and genetic confounding of the associations between ACEs and mental health. Regarding gene–environment correlations, children with higher polygenic scores for mental health problems had a small increase in odds of ACEs. Regarding genetic confounding, elevated risk of mental health problems in children exposed to ACEs was at least partially due to pre-existing genetic risk. However, some ACEs (such as childhood maltreatment and parental mental illness) remained associated with mental health problems independent of genetic confounding. These findings suggest that interventions addressing heritable psychiatric vulnerabilities in children exposed to ACEs may help reduce their risk of mental health problems.

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Fig. 1: Associations between polygenic scores and ACEs in ALSPAC.
Fig. 2: Associations between polygenic scores and ACEs in the ABCD Study.
Fig. 3: Pairwise differences between polygenic scores in their association with ACEs.
Fig. 4: Pairwise differences between ACEs in their association with polygenic risk for mental health problems.
Fig. 5: Structural equation models to estimate the genetic contribution to the associations between ACEs and mental health.
Fig. 6: Genetic confounding of the associations between ACEs and internalizing and externalizing problems.

Data availability

The ABCD Study anonymized data, including all assessment domains, are released annually to the research community. Information on how to access the ABCD data through the NDA is available on the ABCD Study data-sharing webpage: https://abcdstudy.org/scientists_data_sharing.html. Instructions on how to create an NDA study are available at https://nda.nih.gov/training/modules/study.html. The ABCD data repository grows and changes over time. The ALSPAC data are not publicly available, as informed consent for public data-sharing and ethical approval for public data-sharing were not obtained from the participants. Researchers can find the details of how to apply for access to the ALSPAC dataset here: http://www.bristol.ac.uk/alspac/researchers/access/.

Code availability

The analysis code can be found at https://github.com/jr-baldwin/ACEs_mental_health_RR.

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Acknowledgements

We thank all the ALSPAC families who took part in the 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. The UK Medical Research Council and Wellcome (grant no. 102215/2/13/2) and the University of Bristol provide core support for ALSPAC data collection. A comprehensive list of grant funding is available on the ALSPAC website. The GWAS data were generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. Other data used in the preparation of this Article were obtained from the ABCD Study (https://abcdstudy.org), held in the NIMH Data Archive (NDA). This is a multisite, longitudinal study designed to recruit more than 10,000 children aged nine to ten and follow them over ten years into early adulthood. The ABCD Study is supported by the National Institutes of Health and additional federal partners under award numbers U01DA041048, U01DA050989, U01DA051016, U01DA041022, U01DA051018, U01DA051037, U01DA050987, U01DA041174, U01DA041106, U01DA041117, U01DA041028, U01DA041134, U01DA050988, U01DA051039, U01DA041156, U01DA041025, U01DA041120, U01DA051038, U01DA041148, U01DA041093, U01DA041089, U24DA041123 and U24DA041147. A full list of supporters is available at https://abcdstudy.org/federal-partners.html. A listing of the participating sites and a complete listing of the study investigators can be found at https://abcdstudy.org/consortium_members/. ABCD consortium investigators designed and implemented the study and/or provided data but did not necessarily participate in the analysis or writing of this report. This manuscript reflects the views of the authors and may not reflect the opinions or views of the National Institutes of Health or ABCD consortium investigators. We thank G. Sudre for his support with the QC of the ABCD genetic data. This research was funded in whole or in part by the Wellcome Trust (grant no. 215917/Z/19/Z). For the purpose of open access, the authors have applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. L.D.H. is supported by a Career Development Award fellowship from the UK Medical Research Council (no. MR/M020894/1). H.M.S., A.S.F.K., M.M. and L.D.H. work in a unit that receives funding from the University of Bristol and the UK Medical Research Council (grant nos MC_UU_00011/5 and MC_UU_00011/7). H.M.S. and M.M. are supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at the University Hospitals Bristol National Health Service Foundation Trust and the University of Bristol. M.M. and H.M.S. are members of the UK Centre for Tobacco and Alcohol Studies, a UKCRC Public Health Research: Centre of Excellence. A.D. was funded by the Medical Research Council (grant no. P005918) and by the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. The funders had no role in study design, data analysis, decision to publish or preparation of the manuscript.

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Authors and Affiliations

  1. Department of Clinical, Educational and Health Psychology, Division of Psychology and Language Sciences, University College London, London, UK

    Jessie R. Baldwin, Tabea Schoeler, Wikus Barkhuizen, Eamon McCrory & Jean-Baptiste Pingault

  2. Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK

    Jessie R. Baldwin, Andrea Danese & Jean-Baptiste Pingault

  3. MRC Integrative Epidemiology Unit at the University of Bristol, Bristol Medical School, University of Bristol, Bristol, UK

    Hannah M. Sallis, Alex S. F. Kwong, Laura D. Howe & Marcus Munafò

  4. School of Psychological Science, University of Bristol, Bristol, UK

    Hannah M. Sallis & Marcus Munafò

  5. NIHR Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and University of Bristol, Bristol, UK

    Hannah M. Sallis & Marcus Munafò

  6. Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK

    Hannah M. Sallis

  7. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

    Mark J. Taylor, Henrik Larsson, Robert Karlsson & Paul Lichtenstein

  8. Division of Psychiatry, Edinburgh Medical School, University of Edinburgh, Edinburgh, UK

    Alex S. F. Kwong

  9. CNCR, Amsterdam Neuroscience Campus, VU University, Amsterdam, the Netherlands

    Jorim J. Tielbeek

  10. Department of Psychiatry, University of Cambridge, Cambridge, UK

    Varun Warrier

  11. Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK

    Andrea Danese

  12. National and Specialist CAMHS Trauma, Anxiety, and Depression Clinic, South London and Maudsley NHS Foundation Trust, London, UK

    Andrea Danese

  13. Anna Freud National Centre for Children and Families, London, UK

    Eamon McCrory

  14. Psychology Department, Faculty of Social Sciences, Anton de Kom University, Paramaribo, Suriname

    Fruhling Rijsdijk

  15. School of Medical Sciences, Örebro University, Örebro, Sweden

    Henrik Larsson

  16. Gillberg Neuropsychiatry Centre, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden

    Sebastian Lundström

  17. Centre for Ethics, Law and Mental Health (CELAM), Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden

    Sebastian Lundström

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  1. Jessie R. Baldwin
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Contributions

Author contributions are presented according to the CRediT (Contributor Roles Taxonomy). J.R.B.: Conceptualization, methodology, formal analysis, data curation, writing—original draft, writing—review and editing, project administration, funding acquisition. H.M.S.: Software, data curation, writing—review and editing. T.S.: Software, data curation, writing—review and editing. M.J.T.: Software, data curation, writing—review and editing. A.S.F.K.: Writing—review and editing. J.J.T.: Software, resources, writing—review and editing. W.B.: Software, resources, data curation, writing—review and editing. V.W.: Software, writing—review and editing. L.D.H.: Software, data curation, writing—review and editing. A.D.: Conceptualization, writing—review and editing. E.M.: Writing—review and editing. F.R.: Methodology. H.L.: Investigation, writing—review and editing. S.L.: Investigation, writing—review and editing. R.K.: Software, data curation. P.L.: Conceptualization, investigation, writing—review and editing. M.M.: Conceptualization, writing—review and editing, supervision. J.-B.P.: Conceptualization, methodology, formal analysis, data curation, writing—original draft, writing—review and editing, supervision.

Corresponding author

Correspondence to Jessie R. Baldwin.

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Nature Human Behaviour thanks Rachel Latham, Ana Goncalves-Soares and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Supplementary information

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Supplementary Methods 1–3, Results 1 and 2, Discussion, Figs. 1–6, Tables 1–17 and References.

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Baldwin, J.R., Sallis, H.M., Schoeler, T. et al. A genetically informed Registered Report on adverse childhood experiences and mental health. Nat Hum Behav 7, 269–290 (2023). https://doi.org/10.1038/s41562-022-01482-9

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