The Interplay Between Inflammation and Kynurenines on Symptoms of Schizophrenia 公开
Li, Linda (Spring 2019)
Abstract
Schizophrenia is a chronic, debilitating psychiatric disorder characterized by positive symptoms, negative symptoms, and cognitive impairment. Although antipsychotics are effective against positive symptoms, few clinical treatment options are available for negative and cognitive symptoms, which contribute more to poor functional outcome. Several studies have investigated possible biological mechanisms that underlie this pathophysiology. The NMDA receptor hypothesis suggests that hypofunction of this glutamate receptor may contribute to symptoms. Increased inflammation has also been repeatedly linked to abnormal brain circuitry in schizophrenia patients. In particular, inflammation may affect brain circuitry through its stimulation of the peripheral kynurenine pathway, to increase neuroactive compounds called kynurenine metabolites, some of which act as agonists or antagonists of the NMDA receptor. We hypothesized that inflammatory markers and kynurenine metabolites would be higher in concentration for patients relative to controls, and would be positively correlated with each other, as well as with symptom severity and poor cognitive test performance.
After recruiting participants, we assessed the symptom severity of those diagnosed with schizophrenia and assessed cognition in all participants using ten neuropsychological tests. Concentrations of kynurenine metabolites (tryptophan, kynurenine, kynurenic acid, anthranilic acid, and 3-hydroxyanthranilic acid) and of inflammatory markers (cytokines, receptor factors, chemokine MCP1, and acute phase reactant CRP) were measured from blood collected from participants. We compared patients and controls via descriptive statistics for all characteristics and plasma concentrations. Before and after grouping kynurenine metabolites and inflammatory markers into factor groups for simplified analysis, we calculated Pearson correlation coefficients and conducted linear regression analyses to evaluate the relationship between symptoms, kynurenine metabolites, and inflammatory markers.
We found that inflammatory markers were not only highly correlated with but also highly predictive of kynurenine metabolites in schizophrenia patients. However, the relationship between kynurenine metabolites and symptoms was less clear, suggesting that much research has yet to be done to illuminate the complex relationship between kynurenine metabolites and schizophrenia symptoms. Our findings suggest that the interaction of inflammation and kynurenine metabolites may indeed affect symptoms of schizophrenia and may lead to a promising solution to treating negative and cognitive symptoms for schizophrenia patients.
Table of Contents
Introduction……………………………………………………………………………………………………………………..1
Methods…………………………………………………………………………………………………………………………..9
Results……………………………………………………………………………………………………………………………15
Discussion……………………………………………………………………………………………………………………….31
About this Honors Thesis
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