Grey matter volume and its association with cognitive impairment and peripheral cytokines in excited individuals with schizophrenia

Although excited behavior in patients with schizophrenia has been linked to brain structural abnormalities, whether cortical abnormalities in this subgroup are related to cognitive impairment or peripheral immune responses is unknown. We included 28 patients with excitability (EC), 28 patients without excitability (NEC), and 48 healthy controls (HCs) to evaluate the associations. Compared with the HC group, the EC and NEC groups showed significant cognitive impairment and increased serum cytokine levels. Analysis of variance in whole-brain grey matter volume (GMV) showed that the volumes of several brain areas, including the superior frontal gyrus (SFG), superior temporal gyrus, and cingulate gyrus, were decreased in patients with schizophrenia. Notably, the left SFG volume was significantly lower in the EC group than in the NEC group. Spearman correlation analysis showed that elevated cytokines were negatively correlated with the GMV of the bilateral SFG, bilateral inferior parietal gyrus, left anterior cingulate gyrus, right fusiform gyrus and parahippocampal gyrus, which were mainly positive correlated with cognitive tests. Moreover, interleukin 4 may contribute to poor scores on Brief Assessment of Cognition and Neuropsychological Assessment Battery by reducing the left SFG volume (17%, P_mediation = 0.044; and 24%, P_mediation = 0.040, respectively). In conclusion, our results confirm GMV changes in excited patients with schizophrenia, and characterize the GMV as an important interface between inflammatory cytokines and cognitive impairment. Therefore, targeted anti-inflammatory adjuvant antipsychotic therapy may improve cognitive function and volumetric brain abnormalities in these patients.