ArticleNature human behaviour2024
Gene × environment effects and mediation involving adverse childhood events, mood and anxiety disorders, and substance dependence.
Article in Nature human behaviour, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
6 citing papers in PubMed.
- Assessing measurement bias in substance use disorder criteria associated with childhood adversity and genetic liability.Psychology of addictive behaviors : journal of the Society of Psychologists in Addictive Behaviors · 2026Article
- Pathways from Polygenic Risk to Suicidality: Effects of Alcohol Use Disorder and Childhood Adversity.medRxiv : the preprint server for health sciences · 2026Article
- An interpretable machine learning model predicts the interactive and cumulative risks of different environmental chemical exposures on depression.Translational psychiatry · 2025Article
- Polygenic risk and childhood adversity as moderators of drug and alcohol withdrawal symptoms.Drug and alcohol dependence · 2025Article
- Associations of childhood adversity and substance use disorder polygenic scores with disorder severity and diagnostic criteria.Psychological medicine · 2025Article
- Practical, Economic, and Policy Implications of the Leve et al. Paper.Prevention science : the official journal of the Society for Prevention Research · 2024Article
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Authors and funding
16 authors.
Funding
Abstract
Adverse childhood events (ACEs) contribute to the development of mood and anxiety disorders and substance dependence. However, the extent to which these effects are direct or indirect and whether genetic risk moderates them is unclear. We examined associations among ACEs, mood/anxiety disorders and substance dependence in 12,668 individuals (44.9% female, 42.5% African American/Black, 42.1% European American/white). Using latent variables for each phenotype, we modelled direct and indirect associations of ACEs with substance dependence, mediated by mood/anxiety disorders (the forward or 'self-medication' model) and of ACEs with mood/anxiety disorders, mediated by substance dependence (the reverse or 'substance-induced' model). In a subsample, we tested polygenic scores for the substance dependence and mood/anxiety disorder factors as moderators in the mediation models. Although there were significant indirect paths in both directions, mediation by mood/anxiety disorders (the forward model) was greater than that by substance dependence (the reverse model). Greater genetic risk for substance use disorders was associated with a weaker direct association between ACEs and substance dependence in both ancestry groups (reflecting gene × environment interactions) and a weaker indirect association in European-ancestry individuals (reflecting moderated mediation). We found greater evidence that substance dependence reflects self-medication of mood/anxiety disorders than that mood/anxiety disorders are substance induced. Among individuals at higher genetic risk for substance dependence, ACEs were less associated with that outcome. Following exposure to ACEs, multiple pathways appear to underlie the associations between mood/anxiety disorders and substance dependence. Specification of these pathways could inform individually targeted prevention and treatment approaches.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.