Project 3: Brain Biomarker and Clinical Implication of Kynurenine Pathway Dysfunction
The pathophysiology of schizophrenia has been associated with stress and/or an abnormal immune system, but the etiological paths to the disease remain unclear. The kynurenine pathway of tryptophan degradation may provide a mechanistic link as its metabolism in brain and periphery, while not necessarily identical, is influenced by stress, glucocorticoids and the immune system.
However, the field lacks meaningful translation between pre-clinical and clinical observations. There is a lack of a comprehensive clinical effort to understand the proposed connection between impaired kynurenine pathway metabolism and the core symptoms afflicting schizophrenia patients.
The project is designed to fill this void by 1) examining the impact of stress and cytokine-related mechanisms on kynurenine pathway metabolites in schizophrenia patients and 2) evaluating the relevance of these new findings to clinical and brain abnormalities in schizophrenia using an array of state-of-the-art imaging, electrophysiology, and modeling approaches.
The studies will comprehensively investigate the involvement of the kynurenine pathway in mediating the effects of stress and immune function on core clinical and biological abnormalities in schizophrenia, and define key biomarkers associated with the kynurenine pathway in schizophrenia.