Inflammatory, mitochondrial and serotonergic interrelationships in the pathogenesis of major depression

PROJECT NARRATIVE The proposed project proposes brain positron emission tomography (PET) with [11C]ER176, a novel radiotracer for translocator protein (TSPO), a biomarker of glial activation, [11C]WAY-100635, a selective, high-affinity agonist for serotonin 1A receptors, and near infrared spectroscopy (NIRS) to measure mitochondrial function in brain of unmedicated major depression compared with healthy volunteers. This cross-sectional study looks simultaneously at relationships between neuroinflammation, serotonin and mitochondrial function, with respect to presence of illness and severity of major depression. Results are relevant to the mission of the NIH as they have potential to unify major theories of depression pathophysiology, and findings may guide new treatment approaches that can be individualized.