Metabolic Psychiatry: A Conceptual Framework Targeting Metabolic Dysfunction in Psychiatric Disease
Year: 2024
Type: preprint
Abstract: 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.
Authors: Shebani Sethi, Michael Berk, Ana Cristina Andreazza, Lilianne Rivka Mujica-Parodi, Iain Campbell, Harry Campbell, Calogero Longhitano, Natalie Rasgon, Jeff Volek, Cynthia Victoria Calkin, Judith Ford, Robert McCullumsmith, Stephen Cunnane, Timur Liwinski, Dominic D'Agostino, Mark Frye, Zoltan Sarnyai
Institutions: Stanford Medicine, Stanford University, Deakin University, The University of Melbourne, Florey Institute of Neuroscience and Mental Health, Orygen, University of Toronto, Harvard University, Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical Imaging, Stony Brook University, University of Edinburgh, Townsville Hospital, Australian Institute of Tropical Health and Medicine, James Cook University, The Ohio State University, Dalhousie University, San Francisco VA Medical Center, University of California, San Francisco, ProMedica, University of Toledo, Université de Sherbrooke, Centre de recherche sur le vieillissement, University of Basel, Universitäre Psychiatrische Kliniken Basel, University of South Florida, Mayo Clinic
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4405353631