Does sex moderate the effects of early life stress on peripheral inflammation in alcohol use disorder? A preliminary investigation.

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.