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Re-examining the link between childhood maltreatment and substance use disorder: a prospective, genetically informative study

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A Correction to this article was published on 30 April 2021

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Abstract

Childhood maltreatment is considered a risk factor for substance use disorders (SUD), but this is largely based on retrospective self-reports that are subject to recall bias, designs that do not control for familial confounding, or both. The specific contribution of childhood maltreatment to SUD risk thus remains unclear. Here, we evaluated this contribution in a prospective cohort with objectively recorded childhood maltreatment, using a design that allows controlling for familial confounding. We used medical records and registers to study 525 young adults (20–37 years) with prospectively and objectively documented severe maltreatment exposure, 1979 clinical controls (unexposed former child and adolescent psychiatry patients), 1388 matched healthy controls; and their siblings and cousins. We examined the association between maltreatment and SUD using Cox regression models in the population, as well as stratified within siblings in the same family. SUD risk was significantly increased with childhood maltreatment exposure (crude HR: 6.61, 95% CI: 5.81–7.53; HR adjusted for sex, birthyear, externalizing problems, parents’ SUD and socioeconomic factors: 3.50, 95% CI 2.95, 4.16). An approximately threefold elevated SUD risk remained when comparing exposed individuals with their unexposed siblings (adjusted HR: 3.12, 95% CI 2.21, 4.42). We provide estimates of the association between childhood maltreatment and SUD accounting for possible confounds of both recall bias and familial factors. When familial confounding is controlled for, SUD risk attributable to severe childhood maltreatment is decreased, but nevertheless considerable. These findings establish a specific contribution of childhood maltreatment to SUD, underscoring the need for SUD prevention in young people exposed to maltreatment.

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Fig. 1: Cumulative incidence of substance use disorder (SUD) in those exposed to childhood maltreatment versus unexposed clinical and population controls.

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Acknowledgements

This study was funded by the Swedish Research Council 2013–2024 Markus Heilig, grant nos. 2013–07434; the Medical Training and Research Agreement in Östergötland Region, grant no. ALF 2017: LIO-599451 main funding recipient Per Gustafsson; ALF 2018: LIO-692621; and ALF 2019: LIO-791581, main funding recipient Andrea J Capusan, and by the Systembolagets alkoholforskningsråd, grant numbers: 2016–0018, 2017–0075, 2018–0030, and 2019–0007 main recipient Markus Heilig. Funding agencies had no role in the design, execution or analysis of this study or preparation of the manuscript. We would like to thank Erik Onelöv, statistician at Region Östergötland Enterprise Business intelligence System (REBUS) for help with data extraction from the regional patient registers.

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Correspondence to Andrea J. Capusan or Markus Heilig.

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AJC has received speaker’s fees, and/ or scientific advisory board compensation from Lundbeck, Indivior and Camurus, all outside the scope of the current project. MH has received speaker’s fees, research funding and/ or scientific advisory board compensation from Lundbeck, Aelis Farma, Indivior, Brainsway Technologies and Janssen Pharmaceuticals, all outside the scope of current project. PAG has received speaker fees and scientific advisory board compensation from Lilly and Shire pharmaceutical companies all outside the scope of the current project. RK-H, KI, and LMM declares no competing interests.

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Capusan, A.J., Gustafsson, P.A., Kuja-Halkola, R. et al. Re-examining the link between childhood maltreatment and substance use disorder: a prospective, genetically informative study. Mol Psychiatry (2021). https://doi.org/10.1038/s41380-021-01071-8

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