奎硫平联合抗抑郁剂在双相抑郁中的应用

在双相障碍中,应用抗抑郁剂可能诱发躁狂或轻躁狂发作或使循环频率增加。奎硫平作为一种新型抗精神病药,有些学者将其作为心境稳定剂使用。我们采用随机开放性研究,用奎硫平（商品名：思瑞康）合并帕罗西汀（商品名：赛乐特）治疗双相抑郁发作,观察疗效和不良反应,报告如下。     

双相障碍不同首选用药间处方方式、不良反应、经济负担、依从性比较

目的比较首选心境稳定剂和首选抗精神病药治疗的双相障碍患者处方方式、不良反应、经济负担及药物治疗依从性等。方法对河北省11个地市39家精神卫生机构中接受心境稳定剂或抗精神病药治疗的240例双相障碍患者,采用自制调查问卷、临床总体印象病情严重程度量表(clinical global impressions scale-severity of illness,CGI-SI)、不良反应量表(treatment emergent symptom scale,TESS)、药物依从性评定量表(medication adherence rating scale,MARS)进行社会人口学、疾病临床特征、处方方式(联合用药情况)、精神类药物花费、不良反应及治疗依从性等方面的调查。结果首选抗精神病药治疗者(抗精神病药组)152例(63.3%),首选心境稳定剂治疗者(心境稳定剂组)88例(36.7%)。抗精神病药组与心境稳定剂组相比,住院患者构成比(90.1%vs.76.1%)、伴有精神病性症状患者构成比(27.0%vs.11.4%)、不良反应发生率(46.1%vs.31.8%)、精神类药物日花费(中位数12.00元vs.8.37元)和总花费(中位数344.61元vs.144.64元)均较高(P0.05)。但两组间药物处方方式、不良反应严重程度、MARS总分无统计学差异(P0.05)。结论河北省双相障碍患者以首选抗精神病药治疗为主,但首选抗精神病药并未减少之后的联合用药,且不良反应发生率及药物经济负担均明显高于首选心境稳定剂治疗者,所以心境稳定剂仍应作为双相障碍主要首选用药。     

喹硫平联合碳酸锂或丙戊酸钠治疗双相障碍躁狂发作的对照研究

喹硫平控制阳性精神病性症状、双相情感障碍均取得较满意的疗效,不良反应较典型抗精神病药物轻.在治疗双相障碍方面,目前国内外多采用情感稳定剂加抗精神病药物作为治疗方案,既可以较快地控制躁狂,还有预防复发、防止转相的作用[1].本研究分别将喹硫平、氯氮平联合碳酸锂或丙戊酸钠治疗双相躁狂的疗效和安全性进行对照研究,现报道如下.     

双相障碍的药物治疗

本文以美国2000年版双相障碍药物治疗准则为基础，重点介绍锂盐与抗癫痫药物、非典型抗精神病药物、以及新的心境稳定剂等在双相障碍中的应用。     

非典型抗精神病药物联合双心境稳定剂治疗躁狂发作的比较

目的评价非典型抗精神病药物联合双心境稳定剂（丙戊酸钠缓释剂和碳酸锂）治疗躁狂发作的疗效与安全性。方法将69例躁狂发作患者随机分为研究组（n=34）和对照组（n=35）。研究组应用碳酸锂、丙戊酸钠缓释剂以及非典型抗精神病药物治疗6周,对照组应用丙戊酸钠缓释剂联合非典型抗精神病药物,应用Beck-Rafaelsen躁狂评定量表（BRMS）评估病情严重程度。结果治疗后研究组BRMS分值明显下降（基线为27.7±7.8,第6周6.0±3.4）,对照组BRMS分值也下降（分别为28.5±5.5,7.8±2.1）,但是研究组从第2周末起BRMS分值改善比对照组明显。研究组第6周末痊愈率高于对照组（分别为51.4%、28.5%,χ2=5.0,P=0.03）。不良反应发生率无明显差异。结论非典型抗精神病药物联合双心境稳定剂（丙戊酸钠缓释剂联合碳酸锂）比非典型抗精神病药物联合一种心境稳定剂（丙戊酸钠缓释剂）控制躁狂发作效果好。     

10省市双相情感障碍患者药物治疗的现况调查

目的了解国内双相情感障碍患者精神药物的治疗现状。方法按一定的抽样比例，选择10个省市46家专科医院或综合医院精神科同时进行药物处方方式的调查。结果（1）在558例双相情感障碍患者中，躁狂相472例（84．6％），抑郁相86例（15．4％）；555（99．5％）例患者接受精神药物治疗。（2）主要治疗药物为心境稳定剂（80．7％），404例（72．8％）患者使用了抗精神病药。（3）躁狂相患者以心境稳定剂（84．7％）和抗精神病药（81．4％）单一或联合治疗为主，抑郁相患者单一或联合使用抗抑郁药的频率较高（80．2％）。（4）联合两种及其以上药物治疗者占80．2％。（5）145例（26．1％）患者合并使用了苯二氮Zhuo类药。结论国内双相情感障碍药物处方方式与国内外的指南推荐方案基本相符；双相障碍抑郁相抗抑郁药使用频率较高，有待于将来的临床实践论证。     

碳酸锂与丙戊酸钠联合应用的药理和临床研究进展

在临床实践过程中，心境稳定剂联合抗精神病药是针对大多数躁狂发作治疗的即定方案，即便如此联合治疗，也难以使一定比例的患者达到令人满意的效果。因此，在很多国家的双相障碍的治疗指南中，都提到了双心境稳定剂联合应用的问题，其中碳酸锂与丙戊酸钠的联合最为常见。这样的联合在临床效应、不良反应及药物间的相互影响如何，已引起专科医生的关注，故十分有必要对此加以分析及评价。     

2006年我国十省市双相障碍患者药物使用的横断面调查

目的 调查2006年我国10省市双相障碍患者药物治疗现况.方法 根据经济发展水平,按照方便取样原则,在我国10省市41所精神疾病专科医院或综合医院精神科,选择760例年龄16～65岁,符合国际疾病分类第10版精神和行为障碍分类双相情感障碍诊断标准,接受精神药物治疗的双相障碍门诊和住院患者,于2006年5月22-28日使用自制修订的调查问卷调查双相障碍患者药物治疗的处方方式.结果 (1)760例患者中,门诊患者为329例(43.3％);住院患者为431例(56.7％);男436例(57.4％),女318例(41.8％),缺失6例(0.8％)数据.(2) ＞2/3的患者表现为情感高涨(481例,63.3％)、活动增多(513例,67.5％)及思维奔逸(436例,57.4％),162例(21.3％)患者以抑郁表现为主,60例(7.9％)患者伴有精神病性症状,48例(6.3％)患者有自杀观念或行为.住院患者处于急性治疗期、伴精神病性症状的患者比例显著高于门诊患者,并且功能损害更严重.(3)671例(88.3％)患者接受心境稳定剂治疗,主要是碳酸锂和丙戊酸盐;593例(78.0％)患者接受了抗精神病药治疗,按照使用频率高低前5种药物分别是:氯氮平、利培酮、氯丙嗪、奎硫平和氟哌啶醇;142例(18.7％)患者接受了抗抑郁药治疗,其中78例(63.4％)选择新型抗抑郁药选择性5-羟色胺再摄取抑制剂.(4)住院患者使用抗精神病药的比例明显高于门诊患者(87.0％vs 66.3％,x2=46.835,P=0.000),门诊患者接受抗抑郁药治疗的比例显著高于住院患者(22.5％ vs 15.8％,x2=5.538,P=0.019).(5)606例(79.8％)的患者联合2种或3种药物治疗,主要治疗方案是心境稳定剂联合抗精神病药,双相抑郁发作以心境稳定剂联合抗抑郁药治疗为主.(6)患者对治疗药物(抗精神病药、心境稳定剂或抗抑郁药)的选择受不同临床症状的影响(P＜0.05).结论 临床实践中,双相障碍以联合治疗为主,心境稳定剂联合抗精神病药及联合抗抑郁药分别是双相躁狂和双相抑郁患者的主要治疗方案,治疗药物选择主要受患者临床症状的影响.     

有精神病性症状的躁狂发作患者近期疗效比较

目的比较单一经典抗精神病药物（奋乃静）或心境稳定剂（碳酸锂）合并小剂量经典抗精神病药物（奋乃静）治疗有精神病性症状的躁狂发作患者的疗效和安全性;探讨影响患者近期疗效的主要因素。方法（1）将符合入组标准的精神病性症状的躁狂发作患者70例随机分为甲组34例和乙组36例两组进行为期6周治疗。甲组为单一中至大剂量经典抗精神病药物（奋乃静）治疗;乙组为心境稳定剂（碳酸锂）合并中至小剂量经典抗精神病药物（奋乃静）治疗。以Bech—Rafaelsen躁狂量表（BRMs）和临床总体印象量表（CGI）评定患者的疗效,以不良反应症状量表（TESS）评定患者的副反应;（2）采用临床流行病学方法,探讨影响有精神病性症状的躁狂发作患者近期疗效的主要因素。结果（1）在治疗第6周末,甲组患者的临床治愈率38．2％,有效率94．1％（33／34）;乙组的临床治愈率63．9％,有效率100％（36／36）,乙组在临床疗效及药物不良反应上均显著性优于甲组（P〈0．05）;（2）有精神病性症状的躁狂发作患者的近期疗效好,影响有精神病性症状的躁狂发作患者近期疗效的主要因素为患者的起病年龄、病前社会功能、病程特点及患者的精神病性症状与心境的协调性,以急性起病、病前社会功能良好、间歇性病程及患者的精神病性症状与患者心境相协调者的近期疗效为佳。结论（1）心境稳定剂合并小剂量经典抗精神病药物在治疗有精神病性症状的躁狂发作时,临床疗效优于单一经典抗精神病药物治疗且副反应相对少;（2）有精神病性症状的躁狂发作患者的近期疗效好,患者的近期疗效受多种因素的影响。     

典型和非典型抗精神病药合并碳酸锂治疗双相情感障碍躁狂发作的对照研究

目的探讨典型和非典型抗精神病药物合并碳酸锂治疗双相情感障碍躁狂发作患者的疗效。方法将94例双相情感障碍躁狂发作患者分为典型抗精神病药物组（43例）和非典型抗精神病药物组（51例）,进行为期8周的疗效比较。采用Bech-Rafaelsen躁狂量表（BRMS）、临床大体印象量表（CGI）、副反应量表（TESS）以及药物依从性量表分别于入组前和入组第1、2、4、6和8周末时进行评定。结果治疗结束时,两组BRMS评分较入组时均显著减低（P〈0．01）;临床总有效率：典型抗精神病药物组83．7％,非典型抗精神病药物组82．3％;两组疗效差异无显著性。非典型药物组的不良反应较典型组少,药物依从性较典型组高。结论非典型抗精神病药物治疗双相情感障碍躁狂发作的疗效肯定,不良反应较少,安全性高,依从性好,适合临床应用。     

Environmental factors in the development and progression of late-onset Alzheimer＇s disease

Late-onset Alzheimer＇s disease （LOAD） is an age-related neurodegenerative disorder characterized by gradual loss of synapses and neurons, but its pathogenesis remains to be clarified. Neurons live in an environment constituted by neurons themselves and glial cells. In this review, we propose that the neuronal degeneration in the AD brain is partially caused by diverse environmental factors. We first discuss various environmental stresses and the corresponding responses at different levels. Then we propose some mechanisms underlying the specific pathological changes, in particular, hypothalamic-pituitary adrenal axis dysfunction at the systemic level; cerebrovascular dysfunction, metal toxicity, glial activation, and Aβ toxicity at the intercellular level; and kinase-phosphatase imbalance and epigenetic modification at the intracellular level. Finally, we discuss the possibility of developing new strategies for the prevention and treatment of LOAD from the perspective of environmental stress. We conclude that environmental factors play a significant role in the development of LOAD through multiple pathological mechanisms.     

新升格师专生学习倦怠量表的编制

目的编制新升格师专生学习倦怠量表。方法在开放式问卷和访谈的基础上编制量表,施测534例学生,计算量表的信度与效度。结果量表的题目区分度均达到显著性水平;量表由行为回避、情绪低落、成就感低三个维度组成,其结构效度比较理想;量表的α系数为0.905,各因子的α系数也在0.7以上,符合心理测量学的要求。结论新升格师专生的学习倦怠量表具有良好的信度和效度,可以应用于该类学生的检测。     

高血压脑出血的显微外科治疗进展

高血压脑出血（Hypertensive intrac-rebral hemorrhage,HICH）是具有高发病率、高病死率、高致残率的急性脑血管疾病,占所有脑卒中患者的10%-20%,早期病死率可高达49.4%。随着人口老龄化,其发病率逐年提高;而外科手术的干预,使其病死率有所下降,但致残率居高不下。如何提高手术疗效和患者生存质量,一直是神经外科医师努力的方向。微侵袭血肿清除术因其手术创伤小,恢复快,是目前国内治疗高血压脑出血的重要手段。     

神经内镜联合亚低温治疗高血压基底节区脑出血

目的 探讨神经内镜联合亚低温在治疗高血压基底节区脑出血中的临床应用价值.方法 回顾性分析我院神经内镜治疗高血压基底节区脑出血患者40例的临床资料,并对治疗结果进行分析.结果 神经内镜治疗组22例(甲组),神经内镜联合亚低温治疗组18例(乙组),术后3个月根据GCS评分,甲组恢复良好1例,中残4例,重残6例,植物生存6例,死亡5例;乙组恢复良好4例,中残8例,重残3例,植物生存1例,死亡2例,两组比较差异有统计学意义(P＜0.05).两组颅内压比较第1天两者差异不明显,但第2、3天亚低温组颅内压明显降低.结论 神经内镜是治疗高血压基底节区脑出血较为有效的手术方式,联合亚低温治疗能有效降低颅内压,改善术后神经功能恢复,具有较好的临床应用价值.     

阿尔茨海默病治疗的研究进展

阿尔茨海默病（AD）是一种隐匿性起病,进行性恶化的神经退行性疾病,临床最初表现为认知功能障碍,并有可能在5～10年内完全衰退。患者往往伴随严重的记忆力丧失、精神行为异常、人格改变、言语功能障碍,无法独立生活,最终近乎于植物状态。Ferri等采用DISMOD软件在全球60岁以上人群中估计,全球的痴呆患者人数到2040年将达到8llO万左右。     

Effects of p75 neurotrophin receptor knockout on axonal regeneration in a mouse model of facial nerve injury

BACKGROUND： Previous studies have shown that p75 neurotrophin receptor plays an important role in peripheral nerve injury. However, the role of p75 neurotrophin receptor in the regeneration of peripheral nerves remains poorly understood. OBJECTIVE： To study the effect of p75 neurotrophin receptor on facial nerve regeneration. DESIGN, TIME AND SETTING： A randomized controlled experiment was performed in the Regeneration Laboratory of Flinders University, Australia and the Biomedical Laboratory of Dentistry School, Shandong University from March 2005 to February 2006. MATERIALS： Cholera toxin B subunit, fast blue, and biotin rabbit-anti goat IgG were provided by Sigma, USA; goat-anti choleratoxin B subunit ant/body was provided by List Biologicals, USA. METHODS： In p75 neurotrophin receptor knockout and wild type 129/sv mice, the facial nerves on one side were crushed. At days 2 and 4 following injury, regenerating motor neurons in the facial nuclei were labeled by fast blue, and the regenerating axon was labeled by the anterograde tracer choleratoxin B subunit. MAIN OUTCOME MEASURES： Axonal regenerative velocity and number were detected by immunohistochemical staining of choleratoxin B subunit, growth-associated protein, protein gene product 9.5, and calcitonin-gene-related peptide; survival of motor neurons in the facial nuclei was detected by retrograde fast blue. RESULTS： Axonal growth in the facial nerve of p75 neurotrophin receptor knockout mice was significantly less than in wild type mice. At day 7 after injury, the number of regenerating motor neurons in p75 neurotrophin receptor knockout mice remained significantly less than in wild type mice （P 〈 0.05）. The number of positively stained fibers for growth-associated protein-43, protein gene product 9.5, and calcitonin-gene-related peptide in p75 neurotrophin receptor knockout mice was significantly less than in wild type mice （P 〈 0.01）. CONCLUSION： p75 neurotrophin receptor promoted axonal regeneration and enhanced the survival rate of motor neurons following facial nerve injury.     

Edema and neuronal apoptosis in the hippocampus and cortex of elderly rats following transient cerebral ischemia/reperfusion injury

BACKGROUND： Previous studies of cerebral ischemia have used young animals, with an ischemic time greater than 5 minutes （safe time limit）. Despite an increased understanding of neuronal apoptosis, it remains uncertain whether brief cerebral ischemic events of 5 minutes or less damage brain tissue in elderly rodents. OBJECTIVE： To investigate the effects of transient cerebral ischemia （5 minutes）/reperfusion injury on brain cortical and hippocampal edema, aquaporin-4 （AQP-4） expression, and neuronal apoptosis in aged rats, and to compare ischemic sensitivity between cortex and hippocampus. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Institute of Cerebrovascular Disease, Qingdao University Medical School from April 2008 to March 2009. MATERIALS： Rabbit anti-AQP-4 polyclonal antibody, TUNEL kit, and SABC immunohistochemistry kit were purchased from Wuhan Boster Bioengineering, China. METHODS： A total of 160 healthy, male, aged 19-21 months, Wistar rats were randomly assigned to 4 groups： sham-surgery, and ischemia 1-, 3-, and 5-minute groups, with 40 rats in each group. The global cerebral ischemia model was established using the Pusinelli four-vessel occlusion, and the three cerebral ischemia groups were subdivided into reperfusion 12-hour, 1-, 2-, 3-, and 7-day subgroups, with 8 rats in each subgroup. The sham-surgery group was subjected to exposure of the first cervical bilateral alar foramina and bilateral common carotid arteries. MAIN OUTCOME MEASURES： The dry-wet weight assay was used to measure brain water content and histopathology of the cortex and hippocampus was observed following hematoxylin-eosin staining. In addition, cortical and hippocampal AQP-4 expression was detected by streptavidin-biotin complex immunohistochemistry, and neuronal apoptosis was detected by the TUNEL method. RESULTS： There was no significant difference in brain water content or AQP-4 expression in the cortex and hippocampus between ischemia 1- and 3-minute groups and the sham-surgery group or brain water content or AQP-4 expression in the cortex between ischemia 5-minute group and sham-surgery group （P 〉 0.05）. However, brain water content and AQP-4 expression in the hippocampus after 5 minutes of cerebral ischemia were significantly increased compared with the sham-surgery group （P 〈 0.05 or P 〈 0.01）. Several TUNEL-positive cells were observed in the cortex and hippocampus of the sham-surgery group and ischemia 1-minute group, as well as in the cortex of the ischemia 3-minute group. In addition, the number of apoptotic neurons in the hippocampus of ischemia 3-minute group and in the cortex and hippocampus of ischemia 5-minute group was significantly increased （P 〈 0.05 or P 〈 0.01 ）. Neuronal apoptosis was increased after 12 hours of ischemia/reperfusion, and it reached a peak by 2 days （P 〈 0.01）. CONCLUSION： Transient cerebral ischemia （5 minutes） resulted in increased hippocampal edema, AQP-4 expression, and neuronal apoptosis. Moreover, cerebral ischemia had a greater effect on neuronal apoptosis than brain edema or AQP-4 expression, and the hippocampus was more sensitive than the cortex.     

Dysfunctional autophagy in Alzheimer＇s disease： pathogenic roles and therapeutic implications

Neuronal autophagy is essential for neuronal survival and the maintenance of neuronal homeostasis. Increasing evidence has implicated autophagic dysfunction in the pathogenesis of Alzheimer＇s disease （AD）. The mechanisms underlying autophagic failure in AD involve several steps, from autophagosome formation to degradation. The effect of modulating autophagy is context-dependent. Stimulation of autophagy is not always beneficial. During the implementation of therapies that modulate autophagy, the nature of the autophagic defect, the timing of intervention, and the optimal level and duration of modulation should be fully considered.     

Oxidative stress in Alzheimer＇s disease

Oxidative stress plays a significant role in the pathogenesis of Alzheimer＇s disease （AD）, a devastating disease of the elderly. The brain is more vulnerable than other organs to oxidative stress, and most of the components of neurons （lipids, proteins, and nucleic acids） can be oxidized in AD due to mitochondrial dysfunction, increased metal levels, inflammation, and β-amyloid （Aβ） peptides. Oxidative stress participates in the development of AD by promoting Aβ deposition, tau hyperphosphorylation, and the subsequent loss of synapses and neurons. The relationship between oxidative stress and AD suggests that oxidative stress is an essential part of the pathological process, and antioxidants may be useful for AD treatment.