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

Early 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.

This 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.

High-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).

Findings 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.

NCT03594435, registered July 11, 2018.