您好, 访客   登录/注册

帕金森病合并抑郁症的研究进展

来源:用户上传      作者:丁杰 段虹宇 令丽荷 杨旭娟 刘聪发 符庆刚 殷波 王子璇

   【摘要】 帕金森病是最常见、最严重的神经疾病之一,典型的运动症状包括静止性震颤,运动迟缓,肌肉强直,姿势和步态不稳定,在疾病后期导致严重残疾,生活质量下降。与PD相关的最常见的精神疾病是抑郁症,合并性抑郁影响了PD的临床表现和预后,增加了PD的治疗难度,但不幸的是抑郁症经常得不到充分的认识和治疗,随着病情的发展对患者及其照顾者的生活质量产生巨大影响。本文对帕金森病与抑郁症的关系、帕金森合并抑郁症的发病因素、帕金森患者合并抑郁症的发病机制以及帕金森合并抑郁症患者的几种非药物治疗方法进行综述。
   【关键词】 帕金森病 抑郁症 因素 机制 治疗
   Research Advance in Parkinson’s Disease Complicated with Depression/DING Jie, DUAN Hongyu, LING Lihe, YANG Xujuan, LIU Congfa, FU Qinggang, YIN Bo, WANG Zixuan. //Medical Innovation of China, 2020, 17(04): -172
   [Abstract] Parkinson’s disease is one of the most common and serious neurological diseases. Typical motor symptoms include static tremor, motor retardation, muscle stiffness, posture and gait instability, resulting in severe disability and a decline in quality of life at the later stage of the disease. The most common mental illness associated with PD is depression. Concomitant depression affects the clinical manifestation and prognosis of PD and makes the treatment of PD more difficult. Unfortunately, depression is often not fully recognized and treated. With the development of the disease, it has a great impact on the quality of life of patients and their caregivers. This article reviews the relationship between Parkinson’s disease and depression, the pathogenic factors of Parkinson’s disease complicated with depression, the pathogenesis of Parkinson’s disease complicated with depression and several non-drug treatments in patients with Parkinson’s disease complicated with depression.
   [Key words] Parkinson disease Depressive disorder Factor Mechanism treatment
   First-author’s address: Lanzhou University Second Hospital, Lanzhou 730000, China
   doi:10.3969/j.issn.1674-4985.2020.04.042
   帕金森病(Parkinson disease,PD)被认为是除阿尔茨海默病外最常见的神经退行性疾病,也称为低动力性硬性综合征或瘫痪性痉挛,是一种常见的进行性神经退行性疾病,临床表现除了静止性震颤、运动迟缓、肌肉强直、姿势和步态不稳这4种主要的运动症状(motor symptoms,MS)外,还通常伴有许多非运动症状(non-motor symptoms,NMS),如睡眠障碍,神经精神症状、机能失调和感觉障碍等[1-3]。抑郁症(depressive disorder)是帕金森病常见的非运动症状,约35%的PD患者临床上有显著的抑郁症状。PD合并抑郁症严重影响了患者的生活质量,但因抑郁症与PD的非运动症状的区分存在难度,例如疼痛、焦虑等特征;此外大多数患者不能积极主动地向医生交代抑郁相关症状[4-5],这些原因使得PD患者的抑郁症得不到及时有效的治疗。在这里,笔者对帕金森病与抑郁症的关系、帕金森合并抑郁症的发病因素、帕金森患者合并抑郁症的发病机制以及帕金森合并抑郁症患者的几种非药物治疗方法进行综述。
  1 帕金森和抑郁症的关系
   抑郁症和PD之间的关系仍存在爭议,按照文献[6]假说,神经元内α-突触核蛋白沉积物或路易体依次以特定的顺序影响大脑区域:首先是嗅道和下脑干区域受到影响(第1、2阶段),之后向上进入下脑干和中脑(第3、4阶段),最后延伸到基底前脑和大脑皮层(第5、6阶段)。这个模型暗示与情绪症状有关脑干的5-羟色胺中缝核在第2阶段已经受到影响,而与帕金森病的运动症状相关的黑质则在疾病的第3阶段受到影响。根据这一假说,抑郁可以被看作是PD的一种前驱症状,它与后来表现为运动症状的病理生理过程相同。但是抑郁症和PD也可以看作两种独立的疾病,这种观点可以用炎症假说来解释:在大脑的不同区域存在着小胶质细胞,尤其在黑质的致密部更多[7]。PD患者的脑和外周血中可见明显增加的炎症反应。炎症反应时,活化的小胶质细胞可以释放促炎细胞因子、活性氧和补体系统的蛋白质,所有这些介质都会导致神经元损伤,引起神经退化。促炎细胞因子还会引起5-羟色胺、去甲肾上腺素和多巴胺神经传递的改变,这些改变与抑郁症相似。因此抑郁症和帕金森病可以看作由一个共同的病理生理学因素所引起,他们之间没有直接的关系。    此外也有研究认为抑郁是PD的一种前驱症状或是一种危险因素[8]。
   Leentjens[8]在一篇评论中对以上问题进行了详尽的论述,虽然流行病学研究为PD和抑郁症之间的联系提供了有力的证据,但是这种联系的性质尚不清楚。目前的研究主要集中在揭示生物学联系上,但与PD无关的更普遍的抑郁症风险因素也应该得到重视,心理和环境因素也不应被忽视。同时需要扩大研究范围,比较PD和其他抑郁症发病率较高的疾病之间共有的病理生理学因素,以及跨疾病抑郁症病因中心理因素和环境因素之间的相似性。这些方法可以更好地揭示所报道的联系的性质,并为抑郁症与PD的关系提供一个更全面的病因学模型基础。
  2 帕金森合并抑郁症的发病因素
   Neikrug等[9]对86例PD患者进行了快速眼动睡眠行为障碍评估,并对PD患者非运动症状指标进行了评估。研究发现在PD中,快速眼动睡眠行为障碍与更多的非运动症状有关,特别是抑郁症状、睡眠障碍和疲劳的增加。Chagas等[10]在1 451例认知障碍老年人中评估了抑郁与PD之間的关联,在全部样本中,16.1%有抑郁症状,且在PD患者中显著高于对照组,结果表明抑郁与PD的关系随认知功能损害程度的加重而增加。Marinus等[11]综述中将四个研究纳入对抑郁危险因素的Z评分计算中,发现以下因素与抑郁症的未来发展或严重程度相关:抗抑郁药物的使用、认知障碍、病程较长、运动波动、女性、残疾(定义为日常生活活动问题)、左旋多巴剂量较高、低龄。Cui等[12]研究纳入了403例PD患者,这些患者中PD患者抑郁为11.17%,研究发现肿瘤疾病、无伴侣、运动功能障碍、运动障碍、睡眠质量差和焦虑是PD患者发生抑郁的危险因素。秘鲁利马的一项研究纳入了124例患者(平均年龄68.7岁,男性58%),其中60.5%的患者出现抑郁症状,结果显示PD患者抑郁症状的发生与低血症、病情进展快、左旋多巴的使用、MAOIS的使用有关[13]。斯里兰卡的一项对104例特发性帕金森病患者的研究发现,抑郁与PD分期、功能障碍、家庭状况、文化程度、照顾者依赖、伴发糖尿病有显著相关性[14]。一项旨在评估519例非痴呆中国PD患者的患病率并确定导致抑郁症的潜在危险因素的研究发现,非运动症状,睡眠质量差,认知功能障碍和年龄较小是抑郁症的独立预测因素,其中,非运动症状是每个抑郁领域最有力的预测因素[15]。可见,在帕金森氏病患者中,没有关于特定危险因素对未来抑郁发展的相对影响的可靠概念。
   文献[16]研究结果发现6个非PD特异性危险因素(女性、焦虑和/或抑郁病史、日常生活活动能力差、认知状况差)和3个PD特异性危险因素(病程增加、运动症状更严重、左旋多巴的使用)与抑郁有关。但是非PD特异性抑郁危险因素与抑郁的相关性是PD特异性危险因素的3倍,非特异性因素可能比PD特异性因素更容易成为抑郁症的标志。因此,对PD中抑郁的研究不仅应侧重于与PD相关的因素,还应研究范围更广的因素,包括抑郁症的一般危险因素。
  3 帕金森患者合并抑郁症的病理生理机制
   由于抑郁症的解剖和神经化学改变在患者之间是高度不同的,因此还未清楚了解PD合并抑郁症的病理生理学机制[17]。多巴胺能改善情绪障碍,提示多巴胺通路参与PD合并抑郁症的假设[18]。Frosini等[19]一项研究发现PD抑郁和扣带回多巴胺能去神经支配之间有显著的关联,支持了PD抑郁的多巴胺能假说。Lee等[20]在一项大鼠实验中证实多巴胺能系统的破坏会导致5-羟色胺能系统减少,从而导致抑郁行为的表达。文献[21]设计的大鼠PD实验模型提示了外侧缰核可能通过增加中缝核5-羟色胺水平来改善PD大鼠的抑郁样行为,提示外侧缰核可能通过介导黑质多巴胺能神经元对中缝核5-羟色胺能神经元的作用而促进PD大鼠的抑郁样行为。
   然而,PD患者抑郁的机制可能并不局限于多巴胺能系统,因为多巴胺替代只能部分改善PD患者的抑郁症状。PD患者的炎症-免疫反应与抑郁的发生之间存在联系[7],这一假说已在前文进行了介绍。
   有研究显示5-羟色胺系统与情绪变化密切相关,最明显的是抑郁症,同时在帕金森病中5-羟色胺能神经传递存在改变[22-24]。大量研究表明5-HT与多种5-HT受体亚型存在相互作用介导其作用:Liu等[25]研究发现背侧海马5-HT6受体调节单侧6-羟基多巴胺损伤的帕金森病大鼠的抑郁样行为;Zhang等[26]研究发现通过激活和阻断腹侧内侧前额叶皮层(MPFC)边缘前区(PRL)5-HT 7受体诱导的行为效应与腹侧内侧前额叶皮层、腹侧海马、缰核中单胺神经传递的变化有关。同时5-HT7受体激活与抑制与调节了大鼠的抑郁样反应,还有研究发现星形胶质细胞5-HT2B受体基因表达的调控可能与PD所致抑郁症的病理生理演变有关[27]。
   同时,研究发现PD合并抑郁症的患者,其边缘区域较正常组织存在差异。两项研究表明双侧海马和杏仁核体积较小,扣带回前部皮质体积较大与PD患者的抑郁症状有关[28-29]。Lou等[30]一项研究发现抑郁的PD患者右侧扣带皮层的功能连接性增加,左侧背外侧前额叶皮质和右侧上颞叶的功能连接性降低。后扣带皮层的功能连接和抑郁评分之间存在显著负相关,提示脑网络某些节点的功能连接变化可能导致PD患者抑郁。Hu等[31]研究发现PD组右侧小脑、左侧杏仁核与左侧壳核、左侧额下回的功能连接均较正常组明显增强,右侧杏仁核与左侧眶下回、左侧直回、右侧壳核的功能连接较正常组明显减少。边缘区域之间连通性的增加和皮质边缘区域之间连通性的降低可能反映了高阶皮层调节系统对情绪相关边缘区域的影响,这可能导致情绪调节障碍。这些结果证实了PD相关抑郁症状的边缘回路参与的假设。
   此外,Rocha等[32]研究首次证实了PD患者外周血中血管紧张素水平与抑郁症状成正相关,也有研究提出帕金森病的抑郁与hpa轴的失调和Syna所涉及的蛋白质改变有关[33]。   4 帕金森合并抑郁症患者的非药物治疗方法
  4.1 认知行为疗法 认知行为疗法(cognitive behavioral therapy,CBT)能通过心理教育帮助患者,以更现实的、更适应的方式来评估他们的思维,纠正消极的思维。两项研究表明,CBT是治疗PD中抑郁症的有效方法。同时,将患者以小组为单位接受CBT的效率比单独接受CBT要高[34-35]。但在CBT治疗中,一些会对治疗效果产生影响的因素也不能忽视,比如照顾者的参与、运动障碍、婚姻状况[36]。也有学者对远程CBT疗法的效果进行了研究,他们发现通过电话进行的CBT可能是帕金森病抑郁症的一种可行和有益的方法,这将为一些无法在当地获得CBT的患者提供便利[37-38]。但远程CBT治疗中也发现PD患者在联系他们的治疗师和完成任务方面明显不够积极主动,而且对治疗的满意度也较低[39]。此外,为PD抑郁症患者改良并制定个体化的CBT将使得治疗更有效,关于CBT仍需要进行更大规模的随机对照试验[40]。
  4.2 脑深部刺激 脑深部刺激(deep brain stimulation,DBS)涉及一種神经刺激器装置的神经外科植入,该装置将电信号传送到特定的大脑区域[41]。该手术已经成为治疗PD的公认治疗方法,大量研究已经发现单侧或双侧丘脑底核(subthalamic nucleus,STN)和苍白球(globus pallidus,GPI)DBS手术能改善PD患者的抑郁状况[42-43]。同时也有研究指出患者接受单侧GPI DBS手术后的生活质量较STN DBS有更大的改善[44],但是也有患者接受DBS后经历了抑郁、躁狂、冲动、性欲亢进和自我疏离的临床报告,有的患者在接受单侧STN DBS手术后的字母流畅性有所下降而单侧GPI DBS手术没有出现这个问题[45-46]。这些副作用提示PD患者DBS的非运动结局可能取决于主动刺激的位置。为数不多的一项研究支持了DBS结果取决于主动接触位置的概念,研究的结果初步证明,前、中、腹侧STN区的DBS有利于改善PD患者抑郁而不会对运动检查和并发症产生负面影响[46]。因此未来的研究需要使用更复杂的方法,以整合患者的个体神经解剖和刺激参数,更好地了解神经刺激的位置对临床结果的影响,根据患者个体情况量身定制大脑刺激部位[47]。
  4.3 电休克治疗 电休克治疗(electroconvulsive therapy,ECT)也是一项治疗治疗帕金森病抑郁症的有效方法,特别是对于有难治性症状或药物治疗有严重副作用的患者[48]。临床上已经有DBS手术后发生难治性抑郁症的患者经ECT后症状完全逆转的报道[49]。在一项在2002-2013年期间的研究中,
  29例PD病患者被送入神经精神科接受ECT治疗。结果显示ECT有效改善了PD患者的抑郁状况[50]。但不可忽视的是,ECT存在的常见的副作用包括精神错乱、暂时性精神错乱、跌倒、尿潴留等,但很少加剧异常运动和运动症状[51]。
  4.4 重复性经颅磁刺激 重复性经颅磁刺激(repetitive transcranial magnetic stimulation,RTMS)是一种非侵入性脑刺激技术,可根据刺激频率改变大脑对兴奋和抑制的反应。在一项包含10个严重抑郁障碍患者的研究中,接受左侧前额叶背外侧皮质高频RTMS的患者抑郁症状得到了改善[52]。在另一个研究中发现高频双侧初级运动皮质RTMS对PD患者的抑郁和健康相关生活质量有明显的改善作用[53]。一个对RTMS治疗帕金森病抑郁症随机对照临床试验的Meta分析结果表明,RTMS具有与选择性5-羟色胺再摄取抑制剂(serotonin uptake inhibitors,SSRIs)相似的抗抑郁功效,并且可能具有一些改善运动功能的优点[54]。但在有关抑郁症的既定治疗方法之前,还需要更多涉及大样本和采用双盲、假对照设计的多中心研究。
  4.5 其他方法 心身运动采用一种身体-心理-精神的综合方法,通过身体锻炼来实现身心的益处,越来越多人尝试用这一补充的、非药物的方法来控制PD患者的压力和症状,如正念瑜伽[55]、虚拟现实舞蹈[56],这些方法都在改善PD患者抑郁症状方面产生了一定的效果。此外,也有人尝试光照疗法治疗PD患者的抑郁症状,但并没有达到预期结果[57]。
   抑郁症是帕金森患者常见的非运动症状,目前病因及机制不完全明确,需要进一步的研究。帕金森合并抑郁症患者的预后较差,并常常得不到充分的认识,严重影响着患者及照顾者的生活质量,并加重医疗负担。因此,更多的诊断方法以及合理的治疗方案有待制定,以期对帕金森患者的抑郁症状早发现、早治疗、高效治疗,从而改善患者生活质量。
  参考文献
  [1] Khan M A,Quadri S A,Tohid H.A comprehensive overview of the neuropsychiatry of Parkinson’s disease: A review[J].Bull Menninger Clin,2017,81(1):53-105.
  [2] Kalia L V,Lang A E.Parkinson’s disease[J].Lancet,2015,386(9996):896-912.
  [3] Zhang T M,Yu S Y,Guo P,et al.Nonmotor symptoms in patients with Parkinson disease: A cross-sectional observational study[J].Medicine (Baltimore),2016,95(50):e5400.
  [4] Timmer M H M,Van Beek M,Bloem B R,et al.What a neurologist should know about depression in Parkinson’s disease[J].Pract Neurol,2017,17(5):359-368.   [5] Jones J D,Butterfield L C,Song W,et al.Anxiety and Depression Are Better Correlates of Parkinson’s Disease Quality of Life Than Apathy[J].J Neuropsychiatry Clin Neurosci,2015,27(3):213-218.
  [6] Halliday G M,Del Tredici K,Braak H.Critical appraisal of brain pathology staging related to presymptomatic and symptomatic cases of sporadic Parkinson's disease[J].J Neural Transm Suppl,2006(70):99-103.
  [7] Pessoa Rocha N,Reis H J,Vanden Berghe P,et al.
  Depression and cognitive impairment in Parkinson’s disease: a role for inflammation and immunomodulation?[J].Neuroimmunomodulation, 2014, 21(2-3): 88-94.
  [8] Leentjens A F.Parkinson disease: Depression-risk factor or early symptom in Parkinson disease?[J].Nat Rev Neurol,2015,11(8):432-433.
  [9] Neikrug A B,Avanzino J A,Liu L,et al.Parkinson’s disease and REM sleep behavior disorder result in increased non-motor symptoms[J].Sleep Med,2014,15(8):959-966.
  [10] Chagas M H,Moriyama T S,Felicio A C,et al.Depression increases in patients with Parkinson?s disease according to the increasing severity of the cognitive impairment[J].Arq Neuropsiquiatr,2014,72(6):426-429.
  [11] Marinus J,Zhu K,Marras C,et al.Risk factors for non-motor symptoms in Parkinson’s disease[J].Lancet Neurol,2018,17(6):559-568.
  [12] Cui S S,Du J J,Fu R,et al.Prevalence and risk factors for depression and anxiety in Chinese patients with Parkinson disease[J].BMC Geriatr,2017,17(1):270.
  [13] Custodio N,Alva-Diaz C,Moran-Marinos C,et al.Factors associated with depression in patients with Parkinson’s disease A multicenter study in Lima, Peru[J].Dement Neuropsychol,2018,12(3):292-298.
  [14] Ketharanathan T, Hanwella R,Weerasundera R,et al.Major depressive disorder in Parkinson’s disease: a cross-sectional study from Sri Lanka[J].BMC Psychiatry,2014,14:278.
  [15] Zhu J,Lu L,Pan Y,et al.Depression and associated factors in nondemented Chinese patients with Parkinson’s disease[J].Clin Neurol Neurosurg,2017,163:142-148.
  [16] Leentjens A F,Moonen A J,Dujardin K,et al.Modeling depression in Parkinson disease: disease-specific and nonspecific risk factors[J].Neurology,2013,81(12):1036-1043.
  [17] Borgonovo J,Allende-Castro C,Laliena A,et al.Changes in neural circuitry associated with depression at pre-clinical, pre-motor and early motor phases of Parkinson’s disease[J].Parkinsonism Relat Disord,2017,35:17-24.
  [18] Barone P,Poewe W,Albrecht S,et al.Pramipexole for the treatment of depressive symptoms in patients with Parkinson’s disease: a randomised, double-blind, placebo-controlled trial[J].Lancet Neurol,2010,9(6):573-580.   [19] Frosini D,Unti E,Guidoccio F,et al.Mesolimbic dopaminergic dysfunction in Parkinson’s disease depression: evidence from a 123I-FP-CIT SPECT investigation[J].J Neural Transm (Vienna),2015,122(8):1143-1147.
  [20] Lee M,Ryu Y H,Cho W G,et al.Relationship between dopamine deficit and the expression of depressive behavior resulted from alteration of serotonin system[J].Synapse,2015,69(9):453-460.
  [21] Luo X F,Zhang B L,Li J C,et al.Lateral habenula as a link between dopaminergic and serotonergic systems contributes to depressive symptoms in Parkinson’s disease[J].Brain Res Bull,2015,110:40-46.
  [22] Fahn S,Libsch L R,Cutler R W.Monoamines in the human neostriatum: topographic distribution in normals and in Parkinson's disease and their role in akinesia, rigidity, chorea, and tremor[J].J Neurol Sci,1971,14(4):427-455.
  [23] Scatton B,Javoy-Agid F,Rouquier L,et al.Reduction of cortical dopamine, noradrenaline, serotonin and their metabolites in Parkinson’s disease[J].Brain Res,1983,275(2):321-328.
  [24] Shannak K,Rajput A,Rozdilsky B,et al.Noradrenaline, dopamine and serotonin levels and metabolism in the human hypothalamus: observations in Parkinson’s disease and normal subjects[J].Brain Res,1994,639(1):33-41.
  [25] Liu K C,Li J Y,Tan H H,et al.Serotonin(6) receptors in the dorsal hippocampus regulate depressive-like behaviors in unilateral 6-hydroxydopamine-lesioned Parkinson’s rats[J].Neuropharmacology,2015,95:290-298.
  [26] Zhang Q J,Du C X,Tan H H,et al.Activation and blockade of serotonin7 receptors in the prelimbic cortex regulate depressive-like behaviors in a 6-hydroxydopamine-induced Parkinson’s disease rat model[J].Neuroscience,2015,311:45-55.
  [27] Zhang X,Song D,Gu L,et al.Decrease of gene expression of astrocytic 5-HT2B receptors parallels development of depressive phenotype in a mouse model of Parkinson’s disease[J].Front Cell Neurosci,2015,9:388.
  [28] Goto M,Kamagata K,Hatano T,et al.Depressive symptoms in Parkinson’s disease are related to decreased left hippocampal volume: correlation with the 15-item shortened version of the Geriatric Depression Scale[J].Acta Radiol,2018,59(3):341-345.
  [29] Van Mierlo T J,Chung C,Foncke E M,et al.Depressive symptoms in Parkinson’s disease are related to decreased hippocampus and amygdala volume[J].Mov Disord,2015,30(2):245-252.
  [30] Lou Y,Huang P,Li D,et al.Altered brain network centrality in depressed Parkinson’s disease patients[J].Mov Disord,2015,30(13):1777-1784.   [31] Hu X,Song X,Yuan Y,et al.Abnormal functional connectivity of the amygdala is associated with depression in Parkinson’s disease[J].Mov Disord,2015,30(2):238-244.
  [32] Rocha N P,Scalzo P L,Barbosa I G,et al.Peripheral levels of angiotensins are associated with depressive symptoms in Parkinson’s disease[J].J Neurol Sci,2016,368:235-239.
  [33] Caudal D,Alvarsson A,Bjorklund A,et al.Depressive-like phenotype induced by AAV-mediated overexpression of human alpha-synuclein in midbrain dopaminergic neurons[J].Exp Neurol,2015,273:243-252.
  [34] Dobkin R D,Menza M,Allen L A,et al.Cognitive-behavioral therapy for depression in Parkinson's disease: a randomized, controlled trial[J].Am J Psychiatry,2011,168(10):1066-1074.
  [35] Troeung L,Egan S J,Gasson N.A waitlist-controlled trial of group cognitive behavioural therapy for depression and anxiety in Parkinson’s disease[J].BMC Psychiatry,2014,14:19.
  [36] Dobkin R D,Rubino J T,Allen L A,et al.Predictors of treatment response to cognitive-behavioral therapy for depression in Parkinson’s disease[J].J Consult Clin Psychol,2012,80(4):694-699.
  [37] Dobkin R D,Menza M,Allen L A,et al.Telephone-based cognitive-behavioral therapy for depression in Parkinson disease[J].J Geriatr Psychiatry Neurol,2011,24(4):206-14.
  [38] Veazey C,Cook K F,Stanley M,et al.Telephone-administered cognitive behavioral therapy:a case study of anxiety and depression in Parkinson’s disease[J].J Clin Psychol Med Settings,2009,16(3):243-253.
  [39] Koychev I,Okai D.Cognitive-behavioural therapy for non-motor symptoms of Parkinson's disease:a clinical review[J].Evid Based Ment Health,2017,20(1):15-20.
  [40] Dobkin R D,Allen L A,Menza M.Cognitive-behavioral therapy for depression in Parkinson’s disease: a pilot study[J].Mov Disord,2007,22(7):946-952.
  [41] Miocinovic S,Somayajula S,Chitnis S,et al.History, applications, and mechanisms of deep brain stimulation[J].JAMA neurology,2013,70(2):163-171.
  [42] Birchall E L,Walker H C,Cutter G,et al.The effect of unilateral subthalamic nucleus deep brain stimulation on depression in Parkinson’s disease[J].Brain Stimul,2017,10(3):651-656.
  [43] Tao Y,Liang G.Effect of subthalamic nuclei electrical stimulation in the treatment of Parkinson’s disease[J].Cell Biochem Biophys,2015,71(1):113-117.
  [44] Zahodne L B,Okun M S,Foote K D,et al.Greater improvement in quality of life following unilateral deep brain stimulation surgery in the globus pallidus as compared to the subthalamic nucleus[J].J Neurol,2009,256(8):1321-1329.   [45] Gilbert F,Viana J N.A Personal Narrative on Living and Dealing with Psychiatric Symptoms after DBS Surgery[J].Narrat Inq Bioeth,2018,8(1):67-77.
  [46] Dafsari H S,Petry-Schmelzer J N,Ray-Chaudhuri K,et al.
  Non-motor outcomes of subthalamic stimulation in Parkinson’s disease depend on location of active contacts[J].Brain Stimul,2018,11(4):904-912.
  [47] Rughani A,Schwalb J M,Sidiropoulos C,et al.Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on Subthalamic Nucleus and Globus Pallidus Internus Deep Brain Stimulation for the Treatment of Patients With Parkinson’s Disease: Executive Summary[J].Neurosurgery,2018,82(6):753-756.
  [48] Andersen K,Balldin J,Gottfries C G,et al.A double-blind evaluation of electroconvulsive therapy in Parkinson’s disease with “on-off” phenomena[J].Acta neurologica Scandinavica,1987,76(3):191-199.
  [49] Cunningham M G,Yadollahikhales G,Vitaliano G,et al.
  Administration of electroconvulsive therapy for depression associated with deep brain stimulation in a patient with post-traumatic Parkinson’s Disease:a case study[J].BMC Psychiatry,2016,16(1):399.
  [50] Calderon-Fajardo H,Cervantes-Arriaga A,Llorens-Arenas R,et al.Electroconvulsive therapy in Parkinson’s disease[J].Arq Neuropsiquiatr,2015,73(10):856-860.
  [51] Borisovskaya A,Bryson W C,Buchholz J,et al.
  Electroconvulsive therapy for depression in Parkinson’s disease: systematic review of evidence and recommendations[J].Neurodegener Dis Manag,2016,6(2):161-176.
  [52] Shin H W,Youn Y C,Chung S J,et al.Effect of high-frequency repetitive transcranial magnetic stimulation on major depressive disorder in patients with Parkinson’s disease[J].
  J Neurol,2016,263(7):1442-1448.
  [53] Makkos A,Pal E,Aschermann Z,et al.High-Frequency Repetitive Transcranial Magnetic Stimulation Can Improve Depression in Parkinson’s Disease: A Randomized, Double-Blind, Placebo-Controlled Study[J].Neuropsychobiology,2016,73(3):169-177.
  [54] Xie C L,Chen J,Wang X D,et al.Repetitive transcranial magnetic stimulation (rTMS) for the treatment of depression in Parkinson disease: a meta-analysis of randomized controlled clinical trials[J].Neurol Sci,2015,36(10):1751-1761.
  [55] Kwok J Y Y,Kwan J C Y,Auyeung M,et al.Effects of Mindfulness Yoga vs Stretching and Resistance Training Exercises on Anxiety and Depression for People with Parkinson Disease: A Randomized Clinical Trial[J].JAMA Neurol,2019,76(7):755-763.
  [56] Lee N Y,Lee D K,Song H S.Effect of virtual reality dance exercise on the balance, activities of daily living, and depressive disorder status of Parkinson's disease patients[J].J Phys Ther Sci,2015,27(1):145-147.
  [57] Rutten S,Vriend C,Smit J H,et al.Bright light therapy for depression in Parkinson disease: A randomized controlled trial[J].Neurology,2019,92(11):e1145-e1156.
  (收稿日期:2019-08-05) (本文編辑:周亚杰)
转载注明来源:https://www.xzbu.com/6/view-15187211.htm