Pro-inflammatory processes and metabolic syndrome: combined risk of resistance to treatment in patients with schizophrenia from the FACE-SZ cohort

Abstract

Schizophrenia (SZ) is characterized by a variable clinical expression and course peppered/hampered by severe complications. In particular, resistance to treatment (overall-TRS, treatment resistant SZ including UTRS, ultra-TRS) and metabolic syndrome (MetS) are highly prevalent, and both demonstrated to be underpinned, at least partly, by pro-inflammatory processes. Given that such processes also underlie SZ per se, we hypothesized that potential inter-twinning between SZ- and MetS-related inflammatory processes may exert a combined effect on the risk of having overall-TRS/UTRS. A total of 419 outpatients with SZ underwent clinical assessments and blood sample collection. Using the values of circulating levels of eleven cytokines, we built a ratio between pro- and anti-inflammatory components respectively corresponding to the immunoinflammatory response system (IRS) and the compensatory immunoregulatory reflex system (CIRS) which overall reflect the underlying inflammatory status. Such ratios allowed to categorize the patients according to Inflammation and MetS on four categories as follow: Inflammation(+)MetS(+), Inflammation(+)MetS(-), Inflammation(-)MetS(+) and Inflammation(-)MetS(-). Multivariate logistic regression analysis showed that the combination of inflammation and MetS modulate the risk of having the overall-TRS [Inflammation(+)MetS(-): OR=2.28, 95 %CI [1.04-5.00], p = 0.039 and Inflammation(+)MetS(+): OR=4.59, 95 % CI [1.76-11.97], p = 0.002 overall in comparison to Inflammation(-)MetS(-)]. Moreover, we observed that individuals with UTRS are those associated with both inflammation and/or MetS. Our results demonstrated the potential combined effect of MetS and inflammation towards resistance to treatment. Given that overall-TRS/UTRS are unpredictable while both inflammation and MetS can be early detected and managed, our findings shed new light on the possibility to better prevent treatment resistance in SZ.

Keywords: Cytokine; Inflammation; Metabolic syndrome; Resistance to treatment; Schizophrenia.