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Weight Gain, Schizophrenia and Antipsychotics: New Findings from Animal Model and Pharmacogenomic Studies

机译：体重增加，精神分裂症和抗精神病药：动物模型和药物基因组学研究的新发现

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Excess body weight is one of the most common physical health problems among patients with schizophrenia that increases the risk for many medical problems, including type 2 diabetes mellitus, coronary heart disease, osteoarthritis, and hypertension, and accounts in part for 20% shorter life expectancy than in general population. Among patients with severe mental illness, obesity can be attributed to an unhealthy lifestyle, personal genetic profile, as well as the effects of psychotropic medications, above all antipsychotic drugs. Novel “atypical” antipsychotic drugs represent a substantial improvement on older “typical” drugs. However, clinical experience has shown that some, but not all, of these drugs can induce substantial weight gain. Animal models of antipsychotic-related weight gain and animal transgenic models of knockout or overexpressed genes of antipsychotic receptors have been largely evaluated by scientific community for changes in obesity-related gene expression or phenotypes. Moreover, pharmacogenomic approaches have allowed to detect more than 300 possible candidate genes for antipsychotics-induced body weight gain. In this paper, we summarize current thinking on: (1) the role of polymorphisms in several candidate genes, (2) the possible roles of various neurotransmitters and neuropeptides in this adverse drug reaction, and (3) the state of development of animal models in this matter. We also outline major areas for future research.
机译：体重过多是精神分裂症患者中最常见的身体健康问题之一，会增加许多医疗问题的风险，包括2型糖尿病，冠心病，骨关节炎和高血压，部分原因是预期寿命缩短了20％比普通人群要多。在患有严重精神疾病的患者中，肥胖可归因于不健康的生活方式，个人遗传特征以及精神药物的影响，尤其是抗精神病药物。新型“非典型”抗精神病药代表了对较老“典型”药物的重大改进。但是，临床经验表明，这些药物中的一些（但不是全部）可以引起体重的大幅增加。抗精神病相关的体重增加的动物模型和抗精神病受体的基因敲除或过表达的动物转基因模型已被科学界广泛评估为肥胖相关基因表达或表型的变化。此外，药物基因组学方法已允许检测出300多种可能的抗精神病药物引起的体重增加的候选基因。在本文中，我们总结了当前的想法：（1）多态性在几种候选基因中的作用，（2）各种神经递质和神经肽在这种药物不良反应中的可能作用，以及（3）动物模型的发展状态在这件事上。我们还概述了未来研究的主要领域。

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