Schizophrenia is a neuropsychiatric disorder characterized by various symptoms including autonomic imbalance. These disturbances involve almost all autonomic functions and might contribute to poor medication compliance, worsened quality of life and increased mortality. Therefore, it has a great importance to find a potential therapeutic solution to improve the autonomic disturbances. The altered level of kynurenines (e.g., kynurenic acid), as tryptophan metabolites, is almost the most consistently found biochemical abnormality in schizophrenia. Kynurenic acid influences different types of receptors, most of them involved in the pathophysiology of schizophrenia. Only few data suggest that kynurenines might have effects on multiple autonomic functions. Publications so far have discussed the implication of kynurenines and the alteration of the autonomic nervous system in schizophrenia independently from each other. Thus, the coupling between them has not yet been addressed in schizophrenia, although their direct common points, potential interfaces indicate the consideration of their interaction. The present review gathers autonomic disturbances, the impaired kynurenine pathway in schizophrenia, and the effects of kynurenine pathway on autonomic functions. In the last part of the review, the potential interaction between the two systems in schizophrenia, and the possible therapeutic options are discussed.

Recently, morphological impairments have been detected in the brain of a triple-hit rat schizophrenia model (Wisket), and delayed depressive effects of caffeine treatment in both control and Wisket animals have also been shown. The aims of this study were to determine the basal and caffeine-induced acute (30 min) and delayed (24 h) changes in the cerebral ¹⁸fluorodeoxyglucose (¹⁸F-FDG) uptake by positron emission tomography (PET) in control and Wisket rats. No significant differences were identified in the basal whole-brain metabolism between the two groups, and the metabolism was not modified acutely by a single intraperitoneal caffeine (20 mg/kg) injection in either group. However, one day after caffeine administration, significantly enhanced ¹⁸F-FDG uptake was detected in the whole brain and the investigated areas (hippocampus, striatum, thalamus, and hypothalamus) in the control group. Although the Wisket animals showed only moderate enhancements in the ¹⁸F-FDG uptake, significantly lower brain metabolism was observed in this group than in the caffeine-treated control group. This study highlights that the basal brain metabolism of Wisket animals was similar to control rats, and that was not influenced acutely by single caffeine treatment at the whole-brain level. Nevertheless, the distinct delayed responsiveness to this psychostimulant in Wisket model rats suggests impaired control of the cerebral metabolism.