Inflammation, mental health, and alcohol behaviors: Testing links leveraging a familial community sample

Evidence that inflammation is related to poorer mental health largely comes from clinical samples. This pre-registered study examined whether these findings extend to depression, alcohol use, and alcohol use disorder (AUD) in a large sample of community adults (N=972, M= 33.4 years, range=28-49), including a subset of participants from same-sex twin pairs. Analyses primarily examined C-reactive protein (CRP) and a pro-inflammatory cytokine index of three cytokines: interleukin(IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-⍺). This pro-inflammatory index averaged the three cytokines after each was placed on a standard-normal distribution ( M =0[SD=1]). Covariates were age, sex, diet relevant measures, and anti-depressant use. Further, we pre-registered analyses to follow up significant effects in the full sample with co-twin control analyses, which compare twins to each other to control confounds that make twins similar. Depression, alcohol use, and AUD were unrelated to CRP and the pro-inflammatory index. Notably, AUD was associated with lower levels of four individual cytokines (after multiple-testing correction): IL-1β, IL-4, IL-10, and IL-12. In co-twin control analyses, however, these negative associations were nonsignificant, suggesting familial confounders explain these associations. These findings suggest that associations between cytokines and indices of depression and alcohol behavior may not extend from clinical to community samples. Further, although this study is the first that applies the co-twin control approach to rigorously test the link between inflammation and alcohol behavior, it largely converges with studies that suggest confounders explain the putative protective effect of alcohol behaviors on inflammatory markers of health. • This pre-registered study examined whether clinical findings that link inflammation to depression and alcohol behavior extend to a large sample of community adults (N=972). • A subset of participants were from same-sex twin pairs and were included in co-twin control analyses, which control all unmeasured genetic/environmental confounders that make twins similar. • Depression, alcohol use, and alcohol use disorder were unrelated to CRP and a pro-inflammatory index (comprised of IL-1β, IL-6, and TNF-⍺). • Analysis of 10 individual cytokines found that having more alcohol use disorder was associated with lower levels of IL-1β, IL-4, IL-10, and IL-12 in the full sample. • Findings from co-twin control analyses converged with those from other studies, which suggest confounders explain the putative protective effect of alcohol behaviors on inflammatory markers of health.