Neuroinflammation in Schizophrenia: The Key Role of the WNT/β-Catenin Pathway

Schizophrenia is a very complex syndrome involving widespread brain multi-dysconnectivity. Schizophrenia is marked by cognitive, behavioral, and emotional dysregulations. Recent studies suggest that inflammation in the central nervous system (CNS) and immune dysfunction could have a role in the pathogenesis of schizophrenia. This hypothesis is supported by immunogenetic evidence, and a higher incidence rate of autoimmune diseases in patients with schizophrenia. The dysregulation of the WNT/beta-catenin pathway is associated with the involvement of neuroinflammation in schizophrenia. Several studies have shown that there is a vicious and positive interplay operating between neuroinflammation and oxidative stress. This interplay is modulated by WNT/beta-catenin, which interacts with the NF-kB pathway; inflammatory factors (including IL-6, IL-8, TNF-alpha); factors of oxidative stress such as glutamate; and dopamine. Neuroinflammation is associated with increased levels of PPAR gamma. In schizophrenia, the expression of PPAR-gamma is increased, whereas the WNT/beta-catenin pathway and PPAR alpha are downregulated. This suggests that a metabolic-inflammatory imbalance occurs in this disorder. Thus, this research's triptych could be a novel therapeutic approach to counteract both neuroinflammation and oxidative stress in schizophrenia.

Automated summary

Schizophrenia is a complex syndrome characterized by widespread brain multi-dysconnectivity. Recent studies suggest that inflammation and immune dysfunction in the central nervous system (CNS) may play a role in the development of schizophrenia. The dysregulation of the WNT/beta-catenin pathway is associated with neuroinflammation in schizophrenia, and there is a positive interaction between neuroinflammation and oxidative stress. These findings suggest a metabolic-inflammatory imbalance in this disorder.