Proinflammatory Cytokines Predict Brain Metabolite Concentrations in the Anterior Cingulate Cortex of Patients With Bipolar Disorder

Bipolar disorder (BD) is a severe psychiatric illness characterized by abnormalities in the immune/inflammatory function and in brain metabolism. Evidences suggest that inflammation may affect the levels of brain metabolites as measured by single-proton magnetic resonance spectroscopy ( H-MRS). The aim of the study was to investigate whether a wide panel of inflammatory markers (i.e., cytokines, chemokines, and growth factors) can predict brain metabolite concentrations of glutamate, -inositol, -acetylaspartate, and glutathione in a sample of 63 bipolar patients and 49 healthy controls. Three cytokines influenced brain metabolite concentrations: IL-9 positively predicts glutamate, IL-1β positively predicts -inositol, and CCL5 positively predicts -acetylaspartate concentrations. Furthermore, patients showed higher concentrations of glutamate, -inositol, and glutathione and lower concentrations of -acetylaspartate in respect to healthy controls. Our results confirm that inflammation in BD alters brain metabolism, through mechanisms possibly including the production of reactive oxygen species and glia activation.