Lane Hsien-Yuan, Liu Yi-Ching, Huang Chieh-Liang, Chang Yue-Cune, Wu Po-Lun, Lu Chung-Ta, Chang Wen-Ho
Department of Psychiatry and Institute of Medical Sciences, China Medical University, Taichung, Taiwan.
J Clin Psychopharmacol. 2006 Apr;26(2):128-34. doi: 10.1097/01.jcp.0000203196.65710.2b.
A serious side effect of atypical antipsychotics is increased body weight, which leads to further morbidity and nonadherence to medication. It has been suggested that both genetic and nongenetic variables may influence antipsychotics-related weight gain. This study aimed to simultaneously explore the effects of multiple candidate genes and environment factors on body weight of schizophrenia patients who received risperidone, a commonly used atypical antipsychotic agent.
One hundred twenty-three ethnically Han Chinese inpatients with acutely exacerbated schizophrenia were given risperidone monotherapy for up to 42 days. Body weight and clinical manifestations were assessed biweekly. Drug efficacy was measured by the Positive and Negative Syndrome Scale (PANSS), and safety was evaluated by the Extrapyramidal Symptom Rating Scale (ESRS) and the UKU Side Effect Rating Scale. We collected body weight as the response value. Potential prognostic factors were baseline body weight, age, sex, diagnosis subtypes, risperidone dosage, PANSS total scores, treatment duration (weeks 0-6), and 15 genetic variants [across 10 candidate genes: 5-HT1A, 5-HT2A, 5-HT2C, 5-HT6, D1, D2, D3, and alpha1-adrenergic receptors, brain-derived neurotrophic factor (BDNF), and cytochrome P450 2D6 (CYP2D6)]. Because there were repeated assessments, multiple linear regression with the generalized estimating equation (GEE) method was used to adjust the within-subject dependence.
Of 15 genetic polymorphisms examined, 5-HT2A 102-T/C, 5-HT2C -759-C/T, 5-HT6 267-C/T, BDNF 66-Val/Met, and CYP2D6 188-C/T significantly influenced body weight, and so did baseline body weight, age, gender, schizophrenia subtype, and treatment duration and efficacy.
These results suggest that numerous genetic and nongenetic factors affect antipsychotics-related weight gain.
非典型抗精神病药物的一种严重副作用是体重增加，这会导致更多发病情况以及服药依从性降低。有研究表明，遗传和非遗传变量可能都会影响与抗精神病药物相关的体重增加。本研究旨在同时探究多个候选基因和环境因素对接受利培酮（一种常用的非典型抗精神病药物）治疗的精神分裂症患者体重的影响。
123名汉族急性加重期精神分裂症住院患者接受利培酮单药治疗，为期42天。每两周评估一次体重和临床表现。采用阳性与阴性症状量表（PANSS）测量药物疗效，采用锥体外系症状评定量表（ESRS）和UKU副作用评定量表评估安全性。我们收集体重作为反应值。潜在的预后因素包括基线体重、年龄、性别、诊断亚型、利培酮剂量、PANSS总分、治疗时长（第0 - 6周）以及15个基因变异位点[分布于10个候选基因：5 - HT1A、5 - HT2A、5 - HT2C、5 - HT6、D1、D2、D3、α1 - 肾上腺素能受体、脑源性神经营养因子（BDNF）以及细胞色素P450 2D6（CYP2D6）]。由于存在重复测量，故采用广义估计方程（GEE）法进行多重线性回归以调整受试者内相关性。
在所检测的15个基因多态性位点中，5 - HT2A 102 - T/C、5 - HT2C - 759 - C/T、5 - HT6 267 - C/T、BDNF 66 - Val/Met以及CYP2D6 188 - C/T对体重有显著影响，基线体重、年龄、性别、精神分裂症亚型、治疗时长及疗效也有显著影响。
这些结果表明，众多遗传和非遗传因素会影响与抗精神病药物相关的体重增加。
