Metabolic Psychiatry: A Conceptual Framework Targeting Metabolic Dysfunction in Psychiatric Disease

An intricate link exists between metabolic dysfunction and psychiatric disease. Documented deficits in systemic and brain metabolism are seen in several major mental illnesses: schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). We apply lessons from neurology on metabolic signaling between the central nervous system and periphery, metabolic plasticity, and the impact of targeting bioenergetic dysfunction on disease. Targeting this energetic dysfunction may lead to wide-ranging treatment strategies. The epidemics of obesity, metabolic syndrome, and insulin resistance, coupled with the global impact of mental illness, represent an unmet need and gap in psychiatric care. While life saving, some common psychiatric medications can impart undesirable metabolic side effects on an already vulnerable metabolic system. The increased prevalence of metabolic abnormalities among patients with major mental illness and evidence of shared environmental and genetic risk factors have led to a growing interest in understanding underlying biological mechanisms. These factors suggest that addressing metabolic dysfunction, centrally or peripherally, is critical to managing psychiatric illness. Therefore, we propose the incorporation of a metabolic framework into standard clinical psychiatric assessment. The emerging field of metabolic psychiatry explores the physiologic and molecular changes underpinning metabolic dysfunction and psychiatric disease with an aim to identify potential therapeutic and prevention targets. This perspective piece provides a conceptual framework for metabolic psychiatry, linking cerebral glucose hypometabolism, insulin resistance, oxidative stress, mitochondrial dysfunction, and neural network instability in mental illness. We provide a synopsis of the current state of knowledge, where our gaps in understanding lie, and the future directions of incorporating metabolic mechanisms into psychiatric treatment strategies.