The role of genetic polymorphisms in antipsychotic-induced metabolic disorders

Metabolic disorders are particularly common in patients treated with antipsychotic agents. Their incidence in this group is almost 50%. The presence of these disorders significantly reduces the life-span of patients taking these drugs. Treatment-induced body weight gain and abdominal obesity play a key role in the development of these disorders. Various mechanisms participate in this phenomenon and genetic factors are crucial for this process. The objective of this paper is to present the current state of knowledge on the role of genetic polymorphism of genes regulating energy homeostasis in treatment-induced weight gain. The results of genome-wide association studies (GWAS), as well as studies of serotonin 2C receptor, leptin and its receptor, H1, a1 and D2 receptors and other genes involved in the regulation of metabolism and body weight are reviewed and discussed. Current data indicate a multigenic character of this phenomenon. Moreover, the role of particular polymorphisms seems to be specific for individual antipsychotics. In the future this would enable custom tailored drug treatment programmes, in which therapy would be customized according to the patient's genetic profile. This will allow unnecessary adverse complications to be avoided in the form of obesity, metabolic syndrome and preterm death due to cardiovascular disorders. However, so far attempts have not established unambiguously which polymorphisms are responsible for treatment-induced weight gain. Numerous studies have significant methodological limitations, thus restricting the possibility to generalize their results. Further, appropriately designed studies are required.