ABSTRACT
The development of insulin resistance and its corollary of metabolic derangements is a common early event in the course of schizophrenia and chronic mood disorders. However, a broad spectrum of factors contributes to the association between insulin resistance and mental disorders, ranging from genetics to lifestyle characteristics and drug effects. Insulin resistance is implicated in many of the medical comorbidities commonly associated with these psychiatric disorders, including diabetes and atherosclerotic vascular disease. Lifestyle and behavioral characteristics of patients, such as obesity, poor diet, smoking, and lack of exercise offer an opportunity for early, targeted interventions aimed at reducing the personal and societal burden of these already devastating psychiatric illnesses. Significantly higher fasting glucose levels are observed in drug-naı¨ve schizophrenic patients, suggesting an integral role of insulin resistance in this disorder. Similarly, central insulin resistance has been proposed as a possible contributor to the pathophysiology of depression. Additionally, many atypical antipsychotic medications contribute to the development of obesity and insulin resistance. Finally, the hypothesis has been put forward that insulin resistance shares genetic risk factors with schizophrenia and mood disorders. Pathophysiological mechanisms, including stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis also are hypothesized to contribute to insulin resistance in these psychiatric disorders.
