The deficit subtype of schizophrenia is associated with a pro-inflammatory phenotype but not with altered levels of zonulin: Findings from a case-control study

There is evidence that subclinical inflammation and increased gut permeability might be involved in the pathophysiology of schizophrenia. Less is known about these phenomena in patients with the deficit subtype of schizophrenia (D-SCZ) characterized by primary and enduring negative symptoms. Therefore, in the present study we aimed to compare the levels of zonulin (the marker of gut permeability) and immune-inflammatory markers in patients with D-SCZ, those with non-deficit schizophrenia (ND-SCZ) and healthy controls (HCs). A total of 119 outpatients with schizophrenia and 120 HCs were enrolled. The levels of 26 immune-inflammatory markers and zonulin were determined in serum samples. The following between-group differences were significant after adjustment for multiple testing and the effects of potential confounding factors: 1) higher levels of interleukin(IL)- 1β and C-reactive protein (CRP) in patients with D-SCZ compared to those with ND-SCZ and HCs; 2) higher levels of tumor necrosis factor-α and RANTES in both groups of patients with schizophrenia compared to HCs and 3) higher levels of IL-17 in patients with D-SCZ compared to HCs. No significant between-group differences in zonulin levels were found. Higher levels of IL-1β and CRP were associated with worse performance of attention after adjustment for age, education and chlorpromazine equivalents. Also, higher levels of IL-1β were correlated with greater severity of negative symptoms after adjustment for potential confounding factors. In conclusion, individuals with D-SCZ are more likely to show subclinical inflammation. However, findings from the present study do not support the hypothesis that this phenomenon is secondary to increased gut permeability.