Pro-inflammatory cytokines IL-1α, IL-6 and TNF-α in major depressive disorder: Sex-specific associations with psychological symptoms

The pro-inflammatory cytokines IL-1 alpha, IL-6 and TNF-alpha are associated with major depressive disorder, psychological distress, cardiovascular health and obesity. However, there is limited research that has examined multiple associations between these variables, particularly among individuals with major depressive disorder who are treatment free, in comparison with a control cohort, and including analyses of sex differences. In this study, data were analysed from 60 individuals with major depressive disorder and 60 controls, including plasma IL-1 alpha, IL-6 and TNF-alpha, adiposity measures (body mass index, waist circumference), cardiovascular health indices (blood pressure, heart rate) and psychological symptoms (depressive severity, anxiety, hostility, stress). The cytokines were compared by group and sex and correlated with measures of adiposity, cardiovascular health indices and psychological health. Plasma IL-1 alpha and IL-6 were higher in major depressive disorder group versus control, but with a sex interaction for IL-6, with this group difference only among females. TNF-alpha did not differ between groups. IL-1 alpha and IL-6 correlated with depressive severity, anxiety, hostility and stress, whereas TNF-alpha correlated only with anxiety and hostility. Psychopathology was associated with IL-1 alpha in males only and with IL-6 and TNF-alpha in females only. None of the cytokines correlated with body mass index, waist circumference, blood pressure or heart rate. The result of group by sex interaction for IL-6 and sex-specific associations between pro-inflammatory cytokines and psychometrics could be aetiologically important in depression interventions and treatments for females versus males, warranting further investigation.

Automated summary

This study found that pro-inflammatory cytokines IL-1 alpha, IL-6, and TNF-alpha are associated with major depressive disorder, psychological distress, cardiovascular health, and obesity. However, there is limited research on the multiple associations between these variables, especially among untreated individuals with major depressive disorder, compared to a control group, and including sex differences. The study analyzed data from 60 individuals with major depressive disorder and 60 controls, measuring various factors such as plasma levels of cytokines, adiposity measures, cardiovascular health indices, and psychological symptoms. The results showed that plasma IL-1 alpha and IL-6 were higher in the major depressive disorder group compared to the control group, with a sex interaction observed for IL-6. TNF-alpha did not differ between the groups. Moreover, IL-1 alpha and IL-6 were correlated with depressive severity, anxiety, hostility, and stress, while TNF-alpha only correlated with anxiety and hostility. The association between psychopathology and pro-inflammatory cytokines varied by sex. None of the cytokines were correlated with measures of adiposity, cardiovascular health indices, or psychological health. The findings suggest that the group by sex interaction for IL-6 and the sex-specific associations between pro-inflammatory cytokines and psychometrics could have important implications for depression interventions and treatments, particularly for females. Further research is warranted.