Pharmacogenetics Laboratory, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia.
Int J Neuropsychopharmacol. 2020 Nov 26;23(8):496-504. doi: 10.1093/ijnp/pyaa028.
The most common psychiatric complications due to dopaminergic treatment in Parkinson's disease are visual hallucinations and impulse control disorders. Their development depends on clinical and genetic factors.
We evaluated the simultaneous effect of 16 clinical and 34 genetic variables on the occurrence of visual hallucinations and impulse control disorders. Altogether, 214 Parkinson's disease patients were enrolled. Their demographic, clinical, and genotype data were obtained. Clinical and clinical-pharmacogenetic models were built by The Least Absolute Shrinkage and Selection Operator penalized logistic regression. The predictive capacity was evaluated with the cross-validated area under the receiver operating characteristic curve (AUC).
The clinical-pharmacogenetic index for prediction of visual hallucinations encompassed age at diagnosis (OR = 0.99), rapid eye movement (REM) sleep behavior disorder (OR = 2.27), depression (OR = 1.0002), IL6 rs1800795 (OR = 0.99), GPX1 s1050450 (OR = 1.07), COMT rs165815 (OR = 0.69), MAOB rs1799836 (OR = 0.97), DRD3 rs6280 (OR = 1.32), and BIRC5 rs8073069 (OR = 0.94). The clinical-pharmacogenetic index for prediction of impulse control disorders encompassed age at diagnosis (OR = 0.95), depression (OR = 1.75), beta-blockers (OR = 0.99), coffee consumption (OR = 0.97), NOS1 rs2682826 (OR = 1.15), SLC6A3 rs393795 (OR = 1.27), SLC22A1 rs628031 (OR = 1.19), DRD2 rs1799732 (OR = 0.88), DRD3 rs6280 (OR = 0.88), and NRG1 rs3924999 (OR = 0.96). The cross-validated AUCs of clinical and clinical-pharmacogenetic models for visual hallucinations were 0.60 and 0.59, respectively. The AUCs of clinical and clinical-pharmacogenetic models for impulse control disorders were 0.72 and 0.71, respectively. The AUCs show that the addition of selected genetic variables to the analysis does not contribute to better prediction of visual hallucinations and impulse control disorders.
Models could be improved by a larger cohort and by addition of other types of Parkinson's disease biomarkers to the analysis.
帕金森病患者因多巴胺能治疗而导致的最常见精神并发症是幻觉和冲动控制障碍。其发展取决于临床和遗传因素。
我们评估了 16 项临床和 34 项遗传变量对视觉幻觉和冲动控制障碍发生的综合影响。共纳入 214 例帕金森病患者。获取他们的人口统计学、临床和基因型数据。采用最小绝对收缩和选择算子惩罚逻辑回归构建临床和临床-遗传药理学模型。通过交叉验证受试者工作特征曲线下的面积（AUC）评估预测能力。
视觉幻觉预测的临床-遗传药理学指数包括诊断时年龄（OR=0.99）、快速眼动（REM）睡眠行为障碍（OR=2.27）、抑郁（OR=1.0002）、IL6 rs1800795（OR=0.99）、GPX1 s1050450（OR=1.07）、COMT rs165815（OR=0.69）、MAOB rs1799836（OR=0.97）、DRD3 rs6280（OR=1.32）和 BIRC5 rs8073069（OR=0.94）。冲动控制障碍预测的临床-遗传药理学指数包括诊断时年龄（OR=0.95）、抑郁（OR=1.75）、β受体阻滞剂（OR=0.99）、咖啡摄入（OR=0.97）、NOS1 rs2682826（OR=1.15）、SLC6A3 rs393795（OR=1.27）、SLC22A1 rs628031（OR=1.19）、DRD2 rs1799732（OR=0.88）、DRD3 rs6280（OR=0.88）和 NRG1 rs3924999（OR=0.96）。视觉幻觉的临床和临床遗传药理学模型的交叉验证 AUC 分别为 0.60 和 0.59。冲动控制障碍的临床和临床遗传药理学模型的 AUC 分别为 0.72 和 0.71。AUC 表明，将选定的遗传变量添加到分析中不会有助于更好地预测视觉幻觉和冲动控制障碍。
通过更大的队列和将其他类型的帕金森病生物标志物添加到分析中，可以改进模型。
