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Table of Contents Brain Insulin Resistance and Refractory Major Depressive Disorder Cellular Mechanisms of Impaired Brain Glucose Transport Clinical Outcomes from Insulin-Sensitizing Therapies Research Gap and Primary Study Limitations Closing Thoughts Brain Insulin Resistance and Refractory Major Depressive Disorder Psychiatric researchers increasingly identify brain insulin resistance, a metabolic condition where brain cells respond poorly to insulin signals, as a driver of severe mood disorders [1]