Pharmacogenetics of antipsychotic-induced weight gain: review and clinical implications

被引:184
|
作者
Lett, T. A. P. [1 ]
Wallace, T. J. M. [1 ]
Chowdhury, N. I. [1 ]
Tiwari, A. K. [1 ]
Kennedy, J. L. [1 ]
Mueller, D. J. [1 ]
机构
[1] Ctr Addict & Mental Hlth, Pharmacogenet Res Clin, Neurogenet Sect, Toronto, ON M5T 1R8, Canada
关键词
antipsychotics; genetics; personalized medicine; pharmacogenetics; schizophrenia; weight gain; BODY-MASS INDEX; 5-HT2C RECEPTOR GENE; MELANIN-CONCENTRATING HORMONE; GENOME-WIDE ASSOCIATION; SUBUNIT 825T ALLELE; DOUBLE-BLIND PET; ATYPICAL ANTIPSYCHOTICS; PROMOTER REGION; SCHIZOPHRENIA-PATIENTS; HTR2C GENE;
D O I
10.1038/mp.2011.109
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Second-generation antipsychotics (SGAs), such as risperidone, clozapine and olanzapine, are the most common drug treatments for schizophrenia. SGAs presented an advantage over first-generation antipsychotics (FGAs), particularly regarding avoidance of extrapyramidal symptoms. However, most SGAs, and to a lesser degree FGAs, are linked to substantial weight gain. This substantial weight gain is a leading factor in patient non-compliance and poses significant risk of diabetes, lipid abnormalities (that is, metabolic syndrome) and cardiovascular events including sudden death. The purpose of this article is to review the advances made in the field of pharmacogenetics of antipsychotic-induced weight gain (AIWG). We included all published association studies in AIWG from December 2006 to date using the Medline and ISI web of knowledge databases. There has been considerable progress reaffirming previous findings and discovery of novel genetic factors. The HTR2C and leptin genes are among the most promising, and new evidence suggests that the DRD2, TNF, SNAP-25 and MC4R genes are also prominent risk factors. Further promising findings have been reported in novel susceptibility genes, such as CNR1, MDR1, ADRA1A and INSIG2. More research is required before genetically informed, personalized medicine can be applied to antipsychotic treatment; nevertheless, inroads have been made towards assessing genetic liability and plausible clinical application. Molecular Psychiatry (2012) 17, 242-266; doi: 10.1038/mp.2011.109; published online 6 September 2011
引用
收藏
页码:242 / 266
页数:25
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