Pharmacogenetics of leptin in antipsychotic-associated weight gain and obesity-related complications

Amy K. Lee, Jeffrey R. Bishop

Research output: Contribution to journalReview articlepeer-review

29 Scopus citations


Second-generation antipsychotics can greatly improve symptoms of psychosis-spectrum disorders. Unfortunately, these drugs are associated with weight gain, which increases a patient's risk for developing chronic diseases including Type 2 diabetes, cardiovascular diseases or other obesity-related complications. There are interindividual differences in weight gain resulting from antipsychotic drug use that may be explained by pharmacodynamic characteristics of these agents as well as clinical factors. In addition, genetic variations in pathways associated with satiety are increasingly recognized as potential contributors to antipsychotic-associated weight gain. Polymorphisms in the leptin gene, as well as the leptin receptor gene, are potential pharmacogenetic markers associated with these outcomes. This article summarizes evidence for the associations of the leptin gene and the leptin receptor gene polymorphisms with antipsychotic-induced weight gain, potential mechanisms underlying these relationships, and discusses areas for future pharmacogenetic investigation.

Original languageEnglish (US)
Pages (from-to)999-1016
Number of pages18
Issue number7
StatePublished - Jul 2011


  • antipsychotic
  • leptin
  • leptin receptor
  • obesity
  • polymorphism
  • weight gain


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