{"title":"Does sex moderate the effects of early life stress on peripheral inflammation in alcohol use disorder? A preliminary investigation","authors":"","doi":"10.1016/j.drugalcdep.2024.112474","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><div>Early life stress (ELS) increases risk for many medical and psychiatric illnesses, including alcohol use disorder (AUD). Females appear to be more vulnerable than males to adverse ELS-related health outcomes, including heavy alcohol use. The biological processes underlying sex differences in ELS-related drinking outcomes are not well understood. Inflammation is one biological mechanism linking ELS to adult alcohol use. This study tested whether biological sex moderates the relationship between ELS and peripheral inflammation in adults with AUD.</div></div><div><h3>Methods</h3><div>Treatment-seeking males (N=60) and females (N=38) with AUD completed the Adverse Childhood Experiences (ACE) questionnaire and provided blood samples for measures of peripheral C-reactive protein (CRP) and cytokines (TNF-α, IFN-γ, IL-6, IL-8, IL-10). Participants were classified as having “no/moderate-ELS” (ACE=0–3) or “high-ELS” (ACE=4+). A composite cytokine score was calculated using principal component analysis to capture general immune system activation. We tested ELS by sex interactions on CRP and cytokine levels using univariate ANOVA.</div></div><div><h3>Results</h3><div>The no/moderate-ELS group included 37 males and 22 females; the high-ELS group included 23 males and 16 females. There was an ELS group by sex interaction on CRP (p=0.02) and composite cytokine levels (p=0.02). Females in the high-ELS group exhibited greater CRP (p=0.003) and composite cytokine levels (p=0.01) than females in the no/moderate ELS group. There were no ELS group differences in CRP (p=0.9) or composite cytokine levels (p=0.6) in males.</div></div><div><h3>Conclusion</h3><div>Results suggest that sex moderates the effects of ELS on peripheral inflammation in adults with AUD; females with AUD may be more vulnerable to the ELS-related adaptations to the immune system, potentially resulting in a proinflammatory state in adulthood.</div></div>","PeriodicalId":11322,"journal":{"name":"Drug and alcohol dependence","volume":null,"pages":null},"PeriodicalIF":3.9000,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug and alcohol dependence","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0376871624013991","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PSYCHIATRY","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction
Early life stress (ELS) increases risk for many medical and psychiatric illnesses, including alcohol use disorder (AUD). Females appear to be more vulnerable than males to adverse ELS-related health outcomes, including heavy alcohol use. The biological processes underlying sex differences in ELS-related drinking outcomes are not well understood. Inflammation is one biological mechanism linking ELS to adult alcohol use. This study tested whether biological sex moderates the relationship between ELS and peripheral inflammation in adults with AUD.
Methods
Treatment-seeking males (N=60) and females (N=38) with AUD completed the Adverse Childhood Experiences (ACE) questionnaire and provided blood samples for measures of peripheral C-reactive protein (CRP) and cytokines (TNF-α, IFN-γ, IL-6, IL-8, IL-10). Participants were classified as having “no/moderate-ELS” (ACE=0–3) or “high-ELS” (ACE=4+). A composite cytokine score was calculated using principal component analysis to capture general immune system activation. We tested ELS by sex interactions on CRP and cytokine levels using univariate ANOVA.
Results
The no/moderate-ELS group included 37 males and 22 females; the high-ELS group included 23 males and 16 females. There was an ELS group by sex interaction on CRP (p=0.02) and composite cytokine levels (p=0.02). Females in the high-ELS group exhibited greater CRP (p=0.003) and composite cytokine levels (p=0.01) than females in the no/moderate ELS group. There were no ELS group differences in CRP (p=0.9) or composite cytokine levels (p=0.6) in males.
Conclusion
Results suggest that sex moderates the effects of ELS on peripheral inflammation in adults with AUD; females with AUD may be more vulnerable to the ELS-related adaptations to the immune system, potentially resulting in a proinflammatory state in adulthood.
导言早期生活压力(ELS)会增加许多医疗和精神疾病的风险,包括酒精使用障碍(AUD)。与男性相比,女性似乎更容易出现与 ELS 相关的不良健康后果,包括大量饮酒。与 ELS 相关的饮酒结果的性别差异的生物学过程尚不十分清楚。炎症是将 ELS 与成人饮酒联系起来的一种生物机制。本研究测试了生理性别是否会调节 ELS 与 AUD 成人外周炎症之间的关系。方法接受治疗的 AUD 男性(60 人)和女性(38 人)填写了不良童年经历(ACE)问卷,并提供了血液样本,用于测量外周 C 反应蛋白(CRP)和细胞因子(TNF-α、IFN-γ、IL-6、IL-8、IL-10)。参与者被分为 "无/中度ELS"(ACE=0-3)或 "高ELS"(ACE=4+)。使用主成分分析法计算细胞因子的综合得分,以反映免疫系统的总体激活情况。我们使用单变量方差分析检验了 ELS 与性别对 CRP 和细胞因子水平的交互作用。结果 无/中等 ELS 组包括 37 名男性和 22 名女性;高 ELS 组包括 23 名男性和 16 名女性。在 CRP(P=0.02)和综合细胞因子水平(P=0.02)方面,ELS 组与性别之间存在交互作用。高 ELS 组女性的 CRP(p=0.003)和复合细胞因子水平(p=0.01)高于无/中度 ELS 组女性。结论结果表明,性别可调节 ELS 对 AUD 成年患者外周炎症的影响;AUD 女性患者可能更容易受到 ELS 相关免疫系统适应性的影响,从而可能导致成年后的促炎症状态。
期刊介绍:
Drug and Alcohol Dependence is an international journal devoted to publishing original research, scholarly reviews, commentaries, and policy analyses in the area of drug, alcohol and tobacco use and dependence. Articles range from studies of the chemistry of substances of abuse, their actions at molecular and cellular sites, in vitro and in vivo investigations of their biochemical, pharmacological and behavioural actions, laboratory-based and clinical research in humans, substance abuse treatment and prevention research, and studies employing methods from epidemiology, sociology, and economics.