Evidence map›Paper›PMID 37961429›Full record

ArticleResearch square2023

Adverse Childhood Events, Mood and Anxiety Disorders, and Substance Dependence: Gene x Environment Effects and Moderated Mediation.

Henry Kranzler, Christal Davis, Richard Feinn, Zeal Jinwala, Yousef Khan, Ariadni Oikonomou, Damaris Silva-Lopez, Isabel Burton, Morgan Dixon, Jackson Milone and 6 more

Open access · greenAbstract readPreprint
In one paragraph

Article in Research square, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 4 citations in OpenAlex.

  1. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 2 institutions in 1 country.

Henry KranzlerUniversity of Pennsylvania Perelman School of Medicine.ORCID https://orcid.org/0000-0002-1018-0450
Christal DavisUniversity of Pennsylvania Perelman School of Medicine.
Richard FeinnQuinnipiac University.
Zeal JinwalaUniversity of Pennsylvania Perelman School of Medicine.ORCID https://orcid.org/0009-0005-5062-0827
Yousef KhanUniversity of Pennsylvania Perelman School of Medicine.
Ariadni OikonomouUniversity of Pennsylvania Perelman School of Medicine.
Damaris Silva-LopezUniversity of Pennsylvania Perelman School of Medicine.
Isabel BurtonUniversity of Pennsylvania Perelman School of Medicine.
Morgan DixonUniversity of Pennsylvania Perelman School of Medicine.
Jackson MiloneUniversity of Pennsylvania Perelman School of Medicine.
Sarah RamirezUniversity of Pennsylvania Perelman School of Medicine.
Naomi ShifmanUniversity of Pennsylvania.
Daniel LeveyYale School of Medicine.ORCID https://orcid.org/0000-0001-8431-9569
Joel GelernterYale University School of Medicine.ORCID https://orcid.org/0000-0002-4067-1859
Emily HartwellUniversity of Pennsylvania.ORCID https://orcid.org/0000-0002-5137-9714
Rachel KemberUniversity of Pennsylvania.
Yale University · USUniversity of Pennsylvania · US

Funding

Characterizing the phenotypic spectrum associated with genetic liability for alcohol use disorderK01AA028292 · NIAAA · UNIVERSITY OF PENNSYLVANIA · PI KEMBER, RACHEL LORRAINE · 2021 to 2024
$505k
Genetic architecture of substance use disorders and major depressionIK2CX002336 · VA · PHILADELPHIA VA MEDICAL CENTER · PI Emily Hartwell · 2022 to 2026
–
CSRD VA IK2 CX002336NIAAA NIH HHS K01 AA028292
6 · The paper itself

Abstract

Background: 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. Methods: 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). We generated latent variables for each phenotype and modeled direct and indirect effects of ACEs on substance dependence, mediated by mood/anxiety disorders (forward or "self-medication" model) and of ACEs on mood/anxiety disorders, mediated by substance dependence (reverse or "substance-induced" model). In a sub-sample, we also generated polygenic scores for substance dependence and mood/anxiety disorder factors, which we tested as moderators in the mediation models. Results: Although there were significant indirect effects in both directions, mediation by mood/anxiety disorders (forward model) was greater than by substance dependence (reverse model). Greater genetic risk for substance dependence was associated with a weaker direct effect of ACEs on substance dependence in both the African- and European-ancestry groups (i.e., gene-environment interaction) and a weaker indirect effect in European-ancestry individuals (i.e., moderated mediation). Conclusion: We found greater evidence that substance dependence results from self-medication of mood/anxiety disorders than that mood/anxiety disorders are substance induced. Among individuals at higher genetic risk for substance dependence who are more likely to develop a dependence diagnosis, ACEs exert less of an effect in promoting that outcome. Following exposure to ACEs, multiple pathways lead to mood/anxiety disorders and substance dependence. Specification of these pathways could inform individually targeted prevention and treatment approaches.

Identifiers

PMID37961429
PMCPMC10635374
OpenAlexW4387976266

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.