重复经颅磁刺激辅助治疗对精神分裂症患者探索性眼球运动和阴性症状的影响:随机、双盲、伪刺激对照研究(英文)

Effect of adjunctive treatment with repetitive transcranial magnetic stimulation on exploratory eye movements and negative symptoms in schizophrenic patients:a randomized,double-blind,sham-controlled study

背景左侧前额叶背外侧区(dorsolateral prefrontal cortex,DLPFC)是调控眼球运动的关键区域,很可能与精神分裂症的异常探索性眼球运动(exploratory eye movement,EEM)有关。重复经颅磁刺激(repetitive transcranial magneticstimulation,rTMS)刺激大脑的这个区域有可能辅助治疗精神分裂症阴性症状。目的评估rTMS干预对精神分裂症者EEM异常的影响,以及EEM变化与精神分裂症阳性和阴性症状变化之间关系。方法 在上海市精神卫生中心住院的46位精神分裂症患者于2009年6月至2010年2月参加本研究。患者被随机分为rTMS真刺激组(研究组,24例)和rTMS伪刺激组(对照组,22例)。两组均接受标准抗精神病药治疗。rTMS真刺激组每周接受5次rTMS干预,持续4周,应用θ短阵快速脉冲刺激(intermittent theta burst stimulation,iTBS)模式刺激左侧DLPFC。于治疗前及治疗4周末应用阳性与阴性症状量表(Positive and Negative Syndrome Scale,PANSS)盲法评定患者的精神症状和进行EEM检查,EEM检查指标包含凝视点数(number of eye fixations score,NEF)、反应探索分(the responsive search score,RSS)和判别值(differentiation score,D)。结果研究组23例和对照组19例完成研究。经rTMS干预4周后,两组的症状均有明显减轻,但是,接受rTMS辅助治疗患者组的PANSS总分及PANSS阴性症状因子分明显低于对照组。4周后,rTMS真刺激组的NEF分较治疗前有明显升高(改善),而rTMS伪刺激组的NEF分未见明显升高;两组治疗前后RSS及D值的变化均不明显。但是,rTMS真刺激组的NEF中位数变化的百分数(+10%),并没有显著性高于rTMS伪刺激组的NEF中位数变化的百分数(-19%)。结论与标准药物治疗相比,接受4周rTMS刺激左侧前额叶背外侧区辅助治疗的精神分裂症患者的阴性症状更轻,异常探索性眼球运动EEM有一成份也有提高。EEM指标对于治疗的反应方面存在高度个体化变异,这表明需要相对较大的样本来判断特殊治疗是否有效。

Background： The left dorsolateral prefrontal cortex （DLPFC） is one of the crucial areas in ocular control that may be involved in the abnormal Exploratory Eye Movements （EEM） seen in schizophrenia. Repetitive Transcranial Magnetic Stimulation （rTMS） to this same region of the brain is a promising adjunctive therapy for the negative symptoms of schizophrenia.Objective： Assess the effects of rTMS stimulation on EEM abnormalities in schizophrenia and the relationship of changes in EEM to changes in the positive and negative symptoms of schizophrenia.Methods： 46 inpatients with schizophrenia at the Shanghai Mental Health Center between June 2009 and February 2010 were randomly divided into an rTMS group （n =24） and a sham rTMS group （n =22）. Both groups received standard antipsychotic medication. The rTMS group received five adjunctive rTMS treatments per week for four weeks using intermittent theta burst stimulation to the left dorsolateral prefrontal cortex. Patients were evaluated using blinded assessments of the Positive and Negative Syndrome Scale （PANSS） and tests of EEM [ including number of eye fixations score （NEF）, responsive search score （RSS）, and the differentiation score （D） ] before and after the course of treatment.Results： 23 patients in the intervention group and 19 patients in the control group finished the study. Both groups had significant decreases in symptoms after four weeks of treatment but at the end of the treatment period both the total PANSS score and the PANSS negative symptom score were significantly lower in the group that received ad- junctive rTMS. The NEF score increased significantly （ i. e., improved） in the real rTMS group after four weeks of treatment but not in the sham rTMS group; neither group had significant changes in the RSS or D scores. However, the median percent change in the NEF score for the real rTMS group （＋ 10%） was not significantly greater than the median percent change in the sham rTMS group （-19%）.Conclusion： Compared to standard antipsychotic therapy, a four-week course of antipsychotic medication with ad- junctive rTMS was more effective in improving both the negative symptoms of schizophrenia and one component of the abnormal EEM seen in schizophrenia. High individual variability in responsiveness of EEM measures to treat- ment will necessitate relatively large samples to determine whether or not particular treatments are effective.