Role of peripheral cytokines and orbitofrontal cortex subregion structure in schizophrenia agitation

This study aimed to examine the potential involvement of inflammatory imbalance and OFC subregion structure in the pathogenesis of agitation. In this study 119 schizophrenia patients were categorized into different subgroups of agitation using two-step cluster analysis. Peripheral cytokine and the OFC structure were examined in all subjects. Patients were assessed for immune-inflammatory response system and compensatory immunoregulatory reflex system (IRS/CIRS) reflecting the level of inflammatory imbalance. The immune biomarkers mainly include M1 (IL-6, IL-1β, IFN-α and TNF-α), T helper, Th-1 (IL-2, IL-12p70 and IFN-γ), Th-2 (IL-4 and IL-5), Th-17 (IL-17) and T regulatory cytokines (Treg) (IL-10). Compared with the low agitation group, the pro-inflammatory cytokine IL-6 was significantly higher in the high agitation group, as were the levels of the immune biomarkers Th-2, M1, IRS and IRS/CIRS. However, there was no significant difference in the OFC volume and cortical thickness between the two groups. In addition, left lateral OFC volume was negatively correlated with IRS/CIRS in the high agitation group. Moderation model showed that agitation significantly moderated the relationship between left lateral OFC volume and IRS/CIRS. Thus, the present study provides assistance in explaining the etiological mechanisms of agitation in schizophrenia.