Associations of Anger Expression and Social Anxiety with Cortisol, the Cortisol/DHEA-S Ratio, and Interleukin-6 in Psychiatric Outpatients: An Exploratory Cross-Sectional Study

Abstract

Background: Chronic psychological stress can alter hypothalamic–pituitary–adrenal (HPA) axis activity and inflammatory signaling. However, the biological correlates of specific stress-related emotional experiences and expression patterns remain incompletely characterized in clinical populations. We therefore examined the associations of anger expression and social anxiety with HPA-axis-related and inflammatory biomarkers in psychiatric outpatients. Methods: In this exploratory, single-center cross-sectional study, clinical records of 85 adults attending their initial visit to the study clinic were retrospectively reviewed. Anger expression was assessed with the Korean State-Trait Anger Expression Inventory (STAXI-K; n = 61) and social anxiety with the Korean version of the Liebowitz Social Anxiety Scale (LSAS; n = 63). Fasting early morning serum concentrations of cortisol, dehydroepiandrosterone sulfate (DHEA-S) and interleukin-6 (IL-6) were measured. Hierarchical linear regression and partial correlation analyses were conducted adjusting for age, sex and body mass index. Additional analyses included left-censored Tobit models and cross-equation Wald tests. Results: Higher social anxiety scores were associated with higher log-transformed IL-6 (n = 63; β = 0.400, p = 0.001), which was the only association that remained significant after false discovery rate (FDR) correction across the nine main predictor–biomarker tests (q = 0.013). This association also remained significant in the reported sensitivity analyses. Higher anger-out scores were associated with lower morning cortisol (n = 61; β = −0.311, p = 0.022) and a lower log-transformed cortisol/DHEA-S ratio (n = 59; β = −0.278, p = 0.037), but neither remained significant after FDR correction (q = 0.084 for both); the ratio association was also sensitive to covariate adjustment. In separate mutually adjusted analyses (n = 56), social anxiety remained associated with log IL-6 (partial r = 0.295, p = 0.034), whereas the anger-in association was not statistically significant (partial r = −0.026, p = 0.858). Cross-equation Wald tests did not detect statistically significant differences between associations with cortisol and log IL-6. Conclusions: In this exploratory study, the association between social anxiety and higher IL-6 remained significant after FDR correction across the nine main tests and after separate adjustment for depressive symptom severity. The inverse associations of anger-out with morning cortisol and the cortisol/DHEA-S ratio did not survive FDR correction. These findings warrant longitudinal replication and do not establish causality or distinct biological pathways.

The authors' abstract, as published at the source. Brain Sciences, 2026 · DOI ↗