Brain-Derived Neurotrophic Factor Levels and Its Val66Met Gene Polymorphism Predict Tardive Dyskinesia Treatment Response to Ginkgo Biloba
Brain-Derived Neurotrophic Factor Levels and Its Val66Met Gene Polymorphism Predict Tardive Dyskinesia Treatment Response to Ginkgo Biloba
复制标题
脑源性神经营养因子水平及其 Val66Met 基因多态性预测银杏叶治疗迟发性运动障碍的反应
DOI：
10.1016/j.biopsych.2012.04.032
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发表时间：
2012-10-15
影响因子：
10.6
通讯作者：
Kosten, Thomas R.
中科院分区：
文献类型：
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作者：
Zhang, Xiang Yang;Zhang, Wu-Fang;Kosten, Thomas R.
背景：迟发性运动障碍(TD)目前尚无公认的治疗方法或已知的病理生理机制，但低脑源性神经营养因子(BDNF)可能在其病理生理机制中起重要作用。银杏叶(Ginkgo biloba，EGB-761)是一种有效的抗氧化剂，通过提高脑源性神经营养因子水平而起到神经保护作用。我们推测银杏叶提取物761可提高血清BDNF水平，降低TD，尤其是具有BDNF valine 66 to Met(Val66Met)基因型(Val66Met)的精神分裂症患者(Val/Val)。方法：对368例有TD和563例无TD的中国精神分裂症患者和546例健康对照组的血清BDNF水平和BDNF基因Val66Met基因多态性进行分析。大约一半的TD患者(n=157)随后参加了为期12周的双盲、随机、安慰剂对照治疗，每天服用240毫克EGb-761。治疗后复查血清BDNF水平。采用异常不自主运动量表(AIMS)评定临床疗效。结果：TD患者脑源性神经营养因子水平低于非TD患者和健康对照组。与安慰剂治疗相比，EGb-761治疗改善了TD的症状并增加了BDNF水平。AIMS总分的改善与脑源性神经营养因子水平的升高呈正相关。此外，携带Val/Val等位基因的患者AIMS评分改善最大，携带Met/Met等位基因的患者AIMS评分改善最小。结论：脑源性神经营养因子系统可能参与TD的病理生理过程及抗氧化治疗的改善。此外，具有更大BDNF释放遗传潜力的患者(Val/Val在66)可能会从EGB-761治疗中获得更大的TD减少。
Background: Tardive dyskinesia (TD) has no well-accepted treatments or known pathophysiology, but low brain-derived neurotrophic factor (BDNF) may play an important role in its pathophysiology. Ginkgo biloba (EGb-761) is a potent antioxidant that has neuroprotective effects mediated through enhancing BDNF levels. We hypothesized that treatment with EGb-761 would increase serum BDNF levels and reduce TD, particularly among schizophrenia patients who have the BDNF valine 66 to methionine (Val66Met) genotype (Val/Val).Methods: Serum BDNF levels and genotyping for the BDNF gene Val66Met polymorphism were assessed in Chinese schizophrenic patients with (n = 368) and without (n = 563) TD as well as healthy control subjects (n = 546). About half of the TD patients (n = 157) then participated in a double-blind, randomized, placebo-control 12-week treatment with 240 mg per day of EGb-761. Serum BDNF levels were measured again at posttreatment. Clinical efficacy was determined using the Abnormal Involuntary Movement Scale (AIMS).Results: TD patients had lower BDNF levels than the non-TD patients and healthy controls. EGb-761 treatment improved symptoms of TD and increased BDNF levels compared with placebo treatment. Moreover, the improvement of AIMS total score correlated with the increase in BDNF levels. Furthermore, improvement in the AIMS score was greatest in those with the Val/Val allele and lowest with the Met/Met allele.Conclusions: The BDNF system may be implicated in the pathophysiology of TD and its improvement with antioxidant treatment. Furthermore, patients with the genetic potential for greater BDNF release (Val/Val at 66) may obtain a greater reduction in TD from EGb-761 treatment.