Brain glutamine metabolism in schizophrenia

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Project Summary/Abstract Schizophrenia is a disabling psychiatric disorder that affects approximately 1% of the population, and which places an enormous burden on society. While antipsychotic medications are usually effective at controlling the positive symptoms of schizophrenia, persistent negative symptoms and deficits in cognition contribute to significant morbidity and functional impairment. There is increasing evidence that multiple factors may be associated with cognitive deficits in patients with schizophrenia, including both those intrinsic to the brain, behavioral comorbidities, long-term antipsychotic use, as well as systemic factors. Prior studies using magnetic resonance spectroscopy (MRS) have indicated that brain glutamine (Gln) levels are elevated in patients with chronic schizophrenia, and which are negatively correlated with cognitive performance. The underlying mechanism of Gln elevation is unknown, however; it may be related to altered Gln metabolism and/or subclinical increases in blood ammonia levels. The goal of this pilot study is to probe the relationship between brain Gln and blood ammonia levels, both in patients with schizophrenia and control subjects. The relationship between these factors and cognitive function will be evaluated using detailed neuropsychological testing. High-field (7T) MRS will be used, since it provides more accurate estimation of brain Gln compared to MRS performed at lower field strengths. Improved understanding of the relationship between altered Gln and cognitive deficits in schizophrenia may inform future mechanistic studies using back-translational approaches in animal models, and ultimately guide novel therapeutic interventions in schizophrenia.