Impact of atypical antipsychotic therapy on leptin, ghrelin, and adiponectin.
BACKGROUND
Many adverse effects of atypical antipsychotic treatment are associated with antagonism of monoamine receptors; however, data indicate that important metabolic effects, such as hypertriglyceridemia and impairment in glucose/insulin homeostasis, may not be related to these mechanisms, leading investigators to explore alternative hypotheses. Promising candidates include a possible impact of antipsychotics on peptide hormonal regulators of metabolic control such as leptin, ghrelin, and adiponectin. The purpose of this review is to summarize recent data on changes in these hormones during atypical antipsychotic treatment.


METHODS
A Medline search was performed for papers published from January 1999 to January 2007 using key words antipsychotic, atypical antipsychotic, and individual atypical antipsychotic drug names cross-referenced with leptin, ghrelin, and adiponectin.


RESULTS
The bulk of the published work focused on changes in body weight and serum leptin, with far less data on ghrelin, and adiponectin, and nonweight metabolic changes. Leptin changes were directly related to a medication's weight gain liability, with no added antipsychotic effects on leptin signaling. Conflicting results emerged for the other markers, but all three long-term studies on ghrelin showed increased levels in patients on atypical antipsychotics with weight gain liabilities.


CONCLUSIONS
Leptin increases during antipsychotic treatment are a result of weight gain rather than a direct impact of atypical antipsychotics on leptin physiology. Preliminary long-term data show increased ghrelin levels, but this finding must be replicated. The association with antipsychotic effects on glucose and lipid metabolism and these hormones remains virtually unstudied. Future research should indicate whether ghrelin and other peptide hormones may be useful predictors of weight gain or metabolic changes in patients on antipsychotics.
Jin
Hua
H
Department of Psychiatry, University of California at San Diego, USA. hjin@ucsd.edu
Meyer
Jonathan M
JM
Mudaliar
Sunder
S
Jeste
Dilip V
DV
D052242:Adiponectin / Q000097:blood*; D000328:Adult; D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000494:pharmacology* / Q000627:therapeutic use; D015992:Body Mass Index; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D003430:Cross-Sectional Studies; D005260:Female; D054439:Ghrelin / Q000097:blood*; D006801:Humans; D066298:In Vitro Techniques; D020738:Leptin / Q000097:blood* / Q000235:genetics; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000139:chemically induced*; D009765:Obesity / Q000097:blood / Q000139:chemically induced*; D010597:Pharmacogenetics; D011446:Prospective Studies; D051381:Rats; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy
D052242:Adiponectin; D014150:Antipsychotic Agents; D054439:Ghrelin; D020738:Leptin