title: Molecular pathophysiology of metabolic effects of antipsychotic medications.
abstract: Antipsychotic medications are associated with major metabolic changes that contribute to medical morbidity and a significantly shortened life span. The mechanisms for these changes provide us with a broader understanding of central nervous and peripheral organ-mediated metabolic regulation. This paper reviews an extensive literature regarding putative mechanisms for effects of antipsychotic medications on weight regulation and glucose homeostasis as well as potential inherent metabolic risks of schizophrenia itself. We present a model suggesting that peripheral antipsychotic targets play a critical role in drug-induced weight gain and diabetes. We propose that a better understanding of these mechanisms will be crucial to developing improved treatments for serious mental illnesses as well as providing potentially novel therapeutic targets of metabolic disorders including diabetes.
authors.affiliation: Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA; Division of Experimental Therapeutics, New York State Psychiatric Institute, New York, NY 10032, USA.
authors.forename: Jacob S
authors.initials: JS
authors.lastname: Ballon
authors.affiliation: Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA; Naomi Berrie Diabetes Institute, New York, NY 10032, USA.
authors.forename: Utpal
authors.initials: U
authors.lastname: Pajvani
authors.affiliation: Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA; Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY 10032, USA.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Freyberg
authors.affiliation: Naomi Berrie Diabetes Institute, New York, NY 10032, USA; Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: Rudolph L
authors.initials: RL
authors.lastname: Leibel
authors.affiliation: Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA; Division of Experimental Therapeutics, New York State Psychiatric Institute, New York, NY 10032, USA. Electronic address: jlieberman@nyspi.columbia.edu.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Lieberman
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D002149:Energy Intake / Q000187:drug effects / Q000235:genetics; D004734:Energy Metabolism / Q000187:drug effects* / Q000235:genetics*; D018149:Glucose Intolerance / Q000139:chemically induced / Q000378:metabolism; D006801:Humans; D008659:Metabolic Diseases / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects / Q000235:genetics
chemical_list: D014150:Antipsychotic Agents
keywords: antipsychotic drugs; diabetes; insulin resistance; schizophrenia; weight regulation