Kynurenine metabolism and metabolic syndrome in patients with schizophrenia.

Accumulating evidence indicates that a dysregulated kynurenine (KYN) pathway (KP) metabolism may play an important role in the pathogenesis of both schizophrenia and metabolic syndrome (MS). However, the underlying mechanisms remain poorly understood. Here, we aimed to evaluate the potential roles of KP in the pathogenesis of MS in schizophrenia. A total of 160 schizophrenia patients and 70 healthy controls were enrolled in this study. KP metabolites were quantified, and MS scores were calculated, for comparisons between patients and controls. Associations among the indices were explored in both groups. Multiple linear regression analyses were performed to investigate the effects of KP metabolites on MS factors. We observed a significantly higher MS score, lower levels of all KP metabolites, and higher nicotinamide adenine dinucleotide (NAD+)/quinolinic acid (QUNA) in patients than in controls (all p < 0.01). Partial correlation analyses revealed that, in the patient group, QUNA and QUNA/KYN correlated positively with MS score (r = 0.24 and 0.27, respectively, both p < 0.025), and NAD+/QUNA correlated negatively with MS score (r = −0.25, p = 0.002). Results of multiple regression analyses showed significant QUNA × group interactions in the model representing QUNA effects on MS score (β = 0.25) and a significant QUNA/KYN × group interaction in the model representing QUNA/KYN effects on MS score (β = 0.23) (both p < 0.001). Among all factors contributing to MS in schizophrenia, an interactive effect of schizophrenia itself and dysregulated KP plays a contributory role. Conceivably, modulation of the KP could theoretically lead to treating schizophrenia and MS simultaneously. • Kynurenine pathway (KP) metabolism is dysregulated in schizophrenia. • Schizophrenia itself and the dysregulated KP metabolism jointly contribute to the susceptibility to MS in this population. • Modulation of the KP could theoretically lead to treating schizophrenia and MS simultaneously. [ABSTRACT FROM AUTHOR]