Pharmacogenetics of Leptin in Antipsychotic-Associated Weight Gain and Obesity-Related Complications

Abstract

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.

KEYWORDS::

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

Financial & competing interests disclosure

Jeffrey Bishop has received research grant support from Ortho-McNeil Janssen and an honoraria from Eli Lilly and Ortho-McNeil Janssen for CME presentations. These activities were unrelated to the information presented in this manuscript. NIH funding was also received by Jeffrey Bishop: K08MH083888. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

Jeffrey Bishop has received research grant support from Ortho-McNeil Janssen and an honoraria from Eli Lilly and Ortho-McNeil Janssen for CME presentations. These activities were unrelated to the information presented in this manuscript. NIH funding was also received by Jeffrey Bishop: K08MH083888. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.