Institute of Psychiatry, University of Bologna, Bologna, Italy.
PLoS One. 2012;7(10):e44853. doi: 10.1371/journal.pone.0044853. Epub 2012 Oct 15.
We previously investigated a sample of patients during an active phase of psychosis in the search for genetic predictors of haloperidol induced side effects. In the present work we extend the genetic association analysis to a wider panel of genetic variations, including 508 variations located in 96 genes. The original sample included 96 patients. An independent group of 357 patients from the CATIE study served as a replication sample. Outcomes in the investigation sample were the variation through time of: 1) the ESRS and UKU total scores 2) ESRS and UKU subscales (neurologic and psychic were included) related to tremors and 3) ESRS and UKU subscales that do not relate to tremors. Outcome in the replication sample was the presence vs absence of motoric side effects from baseline to visit 1 (~ one month of treatment) as assessed by the AIMS scale test. Rs2242480 located in the CYP3A4 was associated with a different distribution of the UKU neurologic scores through time (permutated p = 0.047) along with a trend for a different haloperidol plasma levels (lower in CC subjects). This finding was not replicated in the CATIE sample. In conclusion, we did not find conclusive evidence for a major association between the investigated variations and haloperidol induced motoric side effects.
我们之前在精神分裂症的活跃期对一组患者进行了研究，旨在寻找预测氟哌啶醇引起的副作用的遗传预测因子。在目前的工作中，我们将遗传关联分析扩展到更广泛的基因变异面板，包括位于 96 个基因中的 508 个变异。原始样本包括 96 名患者。一项来自 CATIE 研究的 357 名患者的独立样本作为复制样本。在研究样本中，通过时间变化的结果为：1）ESRS 和 UKU 总分；2）与震颤相关的 ESRS 和 UKU 亚量表（包括神经和精神方面）；3）与震颤无关的 ESRS 和 UKU 亚量表。在复制样本中，使用 AIMS 量表测试，从基线到第 1 次就诊（约一个月的治疗）评估电机副作用的存在或缺失。位于 CYP3A4 中的 Rs2242480 与 UKU 神经评分的时间分布不同相关（置换检验的 p = 0.047），同时氟哌啶醇的血浆水平也有趋势不同（CC 受试者的水平较低）。这一发现未在 CATIE 样本中得到复制。总之，我们没有发现研究变异与氟哌啶醇引起的运动副作用之间存在主要关联的确凿证据。
