Evidence map›Paper›PMID 41603979›Full record

ArticlePsychopharmacology2026

Peripheral inflammation mediates the relationship between early life stress and alcohol use.

Kaitlin R McManus, Craig Enders, Dylan E Kirsch, Malia Belnap, Erica N Grodin, Lara A Ray

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Psychopharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03594435 (A Randomized Controlled Clinical Trial of the Neuroimmune Modulator Ibudilast for the Treatment of Alcohol Use Disorder), which is not on this map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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.

NCT03594435 phase2completednot on this map

A Randomized Controlled Clinical Trial of the Neuroimmune Modulator Ibudilast for the Treatment of Alcohol Use Disorder

TypeinterventionalSponsorUniversity of California, Los AngelesRan2018 to 2023Enrolled102ConditionsAlcohol Use DisorderArmsIbudilast, Placebo oral capsule
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Kaitlin R McManusDepartment of Psychology, University of California, Los Angeles, 1285 Franz Hall, Box 951563, Los Angeles, CA, 90095-1563, USA.
Craig EndersDepartment of Psychology, University of California, Los Angeles, 1285 Franz Hall, Box 951563, Los Angeles, CA, 90095-1563, USA.
Dylan E KirschDepartment of Psychology, University of California, Los Angeles, 1285 Franz Hall, Box 951563, Los Angeles, CA, 90095-1563, USA.
Malia BelnapNeuroscience Interdepartmental Program, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
Erica N GrodinDepartment of Psychology, University of California, Los Angeles, 1285 Franz Hall, Box 951563, Los Angeles, CA, 90095-1563, USA.
Lara A RayDepartment of Psychology, University of California, Los Angeles, 1285 Franz Hall, Box 951563, Los Angeles, CA, 90095-1563, USA. lararay@psych.ucla.edu.ORCID http://orcid.org/0000-0002-5734-9444

Funding

A Randomized Controlled Clinical Trial of the Neuroimmune Modulator Ibudilast for the Treatment of Alcohol Use DisorderR01AA026190 · NIAAA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI RAY, LARA A. · 2018 to 2021
$2.7M
Doctoral Training in Brain and Behavioral Development During Adolescence (UCLA BBDA)T32HD091059 · NICHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Mirella Dapretto, ANDREW J FULIGNI · 2018 to 2026
$1.7M
Clinical Neuroscience of Alcoholism: Integrating Neuroscience and Clinical TrialsK24AA025704 · NIAAA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LARA A. RAY · 2018 to 2026
$1.3M
Characterizing the Microbiome-Gut-Brain Axis in Individuals with Alcohol Use DisorderK01AA029712 · NIAAA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Erica N Grodin · 2022 to 2026
$819k
A clinical neuroscience approach to understand stress coping in alcohol use disorderF32AA031425 · NIAAA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KIRSCH, DYLAN E · 2024 to 2024
$32k
NIAAA NIH HHS F32 AA031425NIAAA NIH HHS F32AA031425NIAAA NIH HHS K01 AA029712NIAAA NIH HHS K01AA029712NIAAA NIH HHS K24 AA025704NIAAA NIH HHS K24AA025704NIAAA NIH HHS R01 AA026190NIAAA NIH HHS R01AA026190NICHD NIH HHS T32 HD091059
6 · The paper itself

Abstract

rationaleEarly life stress (ELS) is associated with an increased risk for alcohol consumption and development of alcohol use disorder (AUD). Inflammation may be a sex-dependent link between ELS and alcohol use; however, there is limited evidence to support such an association in individuals with AUD.

methodsThis secondary analysis utilized cross-sectional mediation to investigate the role of peripheral inflammation in the relationship between ELS and alcohol consumption (i.e., drinks per drinking day (DPDD)) in treatment-seeking individuals with AUD (n = 99; 60 M/39 F). A cross-sectional moderated mediation analysis was conducted to test sex as a moderator in the link between ELS and inflammation for the above relationship. ELS was conceptualized as a dichotomous "no-moderate ELS" vs. "high-ELS" predictor.

resultsHigh-ELS was associated with higher inflammation (95%CI 0.039,1.558), and higher inflammation was associated with greater DPDD (95%CI 0.024,0.098). A mediation effect emerged where high-ELS influenced greater DPDD through elevated inflammation (ab = 0.044, 95%CI 0.002,0.113). No direct effects between ELS and DPDD emerged (95%CI -0.177,0.108). The interaction between ELS and sex on inflammation was significant for females (95%CI: 0.304,2.719) but not males (95%CI: -0.634,1.270). The mediation relationship between ELS and DPDD through inflammation was significant for females (ab(female) = 0.087, 95%CI: 0.013,0.199) but not males (95%CI: -0.040,0.086).

conclusionsFindings suggest that ELS is associated with recent alcohol use through peripheral inflammation in treatment-seeking individuals with AUD and indicate that this pathway is sex-dependent. Inflammation may be a treatment target for individuals with AUD who have experienced ELS, especially females. CLINICAL TRIALS REGISTRATION: NCT03594435, registered July 11, 2018.

Indexed as

Alcohol useAlcohol use disorderEarly life stressInflammationSex differences

Identifiers

PMID41603979
PMCPMC13011814

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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 Socratic graph.