Crespo-Facorro Benedicto, Prieto Carlos, Sainz Jesus
Department of Psychiatry, School of Medicine, University Hospital Marqués de Valdecilla, IDIVAL, HU Virgen del Rocio-IBIS-Universidad de Sevilla, University of Cantabria, Santander, Spain.
CIBERSAM - Centro Investigación Biomédica en Red Salud Mental, Santander, Spain.
NPJ Schizophr. 2019 Apr 10;5(1):7. doi: 10.1038/s41537-019-0075-y.
Antipsychotic drugs are one of the largest types of prescribed drugs. However, antipsychotic-induced weight gain (AIWG) is a major problem for the patients. AIWG increases cardiovascular and cerebrovascular morbidity and mortality, and reduces quality of life and drug compliance. To characterize changes in gene expression related to AIWG, we sequenced total messenger RNA from the blood samples of two groups of schizophrenia patients before and after 3 months of treatment with antipsychotics. The "weight gain" group was defined by an increase of body mass index (BMI) >1.5 points (18 patients; median BMI increase = 2.69) and the "no weight gain" group was defined by a change of BMI between <1.0 and >-1.0 points (18 patients; median BMI increase = 0.26). We found 115 genes with significant differential expression in the weight gain group before and after medication and 156 in the no weight gain group before and after medication. The weight gain group was significantly enriched with genes related to "obesity" and "BMI" (Fisher; p = 0.0002 and 0.01, respectively) according to the Gene Reference into Function (GeneRIF) database. In the no weight gain group, the enrichment was much smaller (Fisher; p = 0.02 and 0.79). This study is a first step toward detecting genetic factors that cause AIWG and to generating prediction tests in future studies with larger data sets.
抗精神病药物是处方量最大的药物类型之一。然而，抗精神病药物所致体重增加（AIWG）是患者面临的一个主要问题。AIWG会增加心血管和脑血管疾病的发病率及死亡率，并降低生活质量和药物依从性。为了描述与AIWG相关的基因表达变化，我们对两组精神分裂症患者在接受抗精神病药物治疗3个月前后的血液样本中的总信使核糖核酸进行了测序。“体重增加”组的定义为体重指数（BMI）增加>1.5分（18例患者；BMI增加中位数=2.69），“未体重增加”组的定义为BMI变化在<1.0至>-1.0分之间（18例患者；BMI增加中位数=0.26）。我们发现，用药前后体重增加组中有115个基因存在显著差异表达，未体重增加组中有156个基因存在显著差异表达。根据基因功能参考数据库（GeneRIF），体重增加组中与“肥胖”和“BMI”相关的基因显著富集（Fisher检验；p值分别为0.0002和0.01）。在未体重增加组中，富集程度要小得多（Fisher检验；p值分别为0.02和0.79）。本研究是朝着检测导致AIWG的遗传因素以及在未来更大数据集的研究中生成预测测试迈出的第一步。
