Deficit schizophrenia: an update

The criteria for deficit schizophrenia were designed to define a group of patients with enduring, primary (or idiopathic) negative symptoms. In 2001, a review of the literature suggested that deficit schizophrenia constitutes a disease separate from nondeficit forms of schizophrenia. Here we provide a review of new studies, not included in that paper, in which patients with deficit schizophrenia and those with nondeficit schizophrenia were compared on dimensions typically used to distinguish diseases: signs and symptoms, course of illness, pathophysiological correlates, risk and etiological factors, and treatment response. Replicated findings and new evidence of double dissociation supporting the separate disease hypothesis are highlighted. Weaknesses in research and treatment options for these patients are also emphasized.     

帕金森病单纯淡漠的临床特征及发生机制

帕金森病(Parkinson disease,PD)是常见的神经变性疾病,除静止性震颤、运动迟缓、肌强直、步态和姿势障碍等运动症状外,近年研究发现其还存在神经精神、睡眠、感觉及自主神经障碍等多种非运动症状。PD单纯淡漠是不伴痴呆和抑郁的淡漠,其与运动症状及多种非运动症状相关,严重影响患者的日常生活能力及生活质量。PD单纯淡漠的发生涉及神经解剖、神经病理、神经生化及神经免疫炎症等机制。本文将对PD单纯淡漠的临床特征及发生机制进行阐述。     

Dopamine Modulates Option Generation for Behavior

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帕金森病研究进展

帕金森病(Parkinson’s disease,PD)是一种多发于中老年期的,以黑质多巴胺能神经元选择性变性为主要病理改变的神经系统退行性疾病。目前,对该病的病因和发病机制还不清楚,尚未建立特异的、灵敏的预警和早期诊断体系以及确切有效的神经保护和治疗的方法。PD的发病与人口老龄化密切相关,随着我国老龄化社会的到来,PD发病率不断增加,给社会和经济都带来严重的危害,因此,越来越受到国家和政府的关注。本世纪以来,科技部先后设立"神经变性病的机制和防治的基础研究"以及"帕金森病发病机制及防治策略的研究"两个973计划项目,以求系统、深入研究PD的病因,神经元选择性、进行性变性死亡的关键机制以及寻找能延缓或阻断疾病的药物等防治新策略,期望推动我国的PD研究,为建立PD防治的新理论、新策略和新技术等奠定扎实的基础。对这两个973项目PD研究团队的主要原创性工作进行综述。     

Behavioural and psychological symptoms of dementia in primary care: a survey of general practitioners in Ireland

Background Management of neuropsychiatric symptoms is a challenging task in primary care. Aims To assess self-reported confidence and knowledge of general practitioners (GPs) regarding the identification and management of behavioural and psychological symptoms of dementia (BPSD).Methods A self-designed two-page paper questionnaire was sent to a random sample of 160 GPs practising in north Dublin. They were asked to evaluate their confidence and knowledge on several aspects of diagnosis and management of BPSD.Results Completed questionnaires were returned from 109 GPs (response rate = 68%), of which 106 were usable. In general, GPs were somewhat critical of their self-reported skills in diagnosing (76.4%) and managing (77.4%) BPSD, as well as in discriminating BPSD from other behavioural disturbances (71.7%). Many of them (67.9%) also encountered difficulty accessing specialist services. There was no correlation between demographic characteristics of GPs or patient caseload with respect to their responses to questionnaire items. Although many GPs (92.5%) highly valued the important role of non-pharmacological interventions in BPSD, none of them reported recommending these in their daily practice.Conclusions Despite the fact that GPs have a wealth of knowledge about BPSD, they are largely critical of their knowledge and management skills of these symptoms. Efforts should be focused on supporting GPs by means of educational interventions that consider all aspects of dementia, but additionally highlight the more challenging neuropsychiatric components of the illness. Health services need to be structured in a way that promotes collaboration between GPs and mental health professionals for a seamless delivery of care.     

丘脑底核-深部脑刺激术术后淡漠的研究进展

帕金森病(Parkinson's disease,PD)是一种由于中脑黑质以及其他核团结构的多巴胺能神经元变性所致的以进行性运动功能障碍为主要表现的疾病。近年来,双侧高频刺激的丘脑底核-深部脑刺激术(STN-DBS)治疗PD效果确切,疗效较好,但其出现了术后淡漠等类似副作用,严重影响了PD治疗效果和患者的生活质量,引起了临床医生的高度重视。本文对STN-DBS术后淡漠发病情况、表现及治疗进行综述,为临床诊治提供思路。     

Impact of limiting visual input on gait: Individuals with Parkinson disease,age-matched controls,and healthy young participants

Normal and limited vision gait was investigated in individuals with Parkinson disease (PD), healthy older and healthy young individuals. Participants walked a GAITRite mat with normal vision or vision of lower limbs occluded. Results indicate individuals with PD walked more slowly, with shorter and wider steps, and spent more time in double support with limited vision as compared to full vision. Healthy young and old individuals took shorter steps but were otherwise unchanged between conditions.     

帕金森病的研究进展

帕金森病是一种中老年人常见的运动障碍性疾病,年龄是最主要的危险因素,已经显示出遗传倾向性的一些易感基因包括α-突触核蛋白、LRRK-2、GBA等也是重要的发病因素。多巴胺的替代治疗是帕金森病最重要的治疗办法,可以显著减轻病人的运动障碍,胚胎干细胞移植及基因治疗都是在探索中及具广阔前景的治疗办法。     

Adult neurogenesis in the mammalian brain

New neurons are generated throughout life in distinct areas of the mammalian brain. This process, called adult neurogenesis, has challenged previously held concepts about adult brain plasticity and opened novel therapeutic avenues to treat certain neuro-psychiatric diseases. Here, we review the current knowledge regarding the fate and potency of neural stem cells (NSCs), as well as the mechanisms underlying neuronal differentiation and subsequent integration. Furthermore, we discuss the functional significance of adult neurogenesis in health and disease, and offer brief insight into the future directions of the adult neurogenesis field.     

Residue Glu83 plays a major role in negatively regulating α-synuclein amyloid formation

α-Synuclein (α-syn) amyloid filaments are the major ultrastructural component of pathological inclusions that define several neurodegenerative disorders, including Parkinson disease and other disorders that are collectively termed synucleinopathies. Since the aggregation of α-syn is associated with the etiology of these diseases, defining the molecular elements that influence this process may have important therapeutics implication. The deletions of major portions of the hydrophobic region of α-syn (Δ74-79 and Δ71-82) impair the ability to form amyloid. However, mutating residue E83 to an A restored the ability of these proteins to form amyloid. Additionally supporting an inhibitory role of residue E83 on amyloid formation, mutating this residue to an A enhanced amyloid formation in the presence of small molecule inhibitors, such as dopamine and EGCG. Our data, therefore, suggest that the presence and placement of the highly charged E83 residue plays a significant inhibitory role in α-syn amyloid formation and these findings provide important insights in the planning of therapeutic agents that may be capable of preventing α-syn amyloid formation.     

帕金森病衣架样疼痛及治疗策略

目的:衣架样疼痛(coat-hanger ache,CHA)是帕金森病(Parkinson disease,PD)疼痛的一个少见类型,本文研究帕金森病合并衣架样疼痛的血压状况及治疗策略。方法:本文以15例伴有CHA的PD患者为研究对象,以不伴有CHA年龄、性别大致匹配的PD病人为对照,观察两组病人卧立位血压的变化及CHA组直立后出现疼痛的时间和评分,找到相应的治疗措施。结果:CHA组伴有体位性低血压(orthostatic hypotension,OH)的比例为80%,明显高于对照组(33%),站立后出现疼痛的时间为7.2±1.2,疼痛评分为3.5±2.1,给予改善OH的物理及药物治疗,大部分DHA病人有效。结论:PD病人伴有CHA可能与OH有关,改善血压状况后部分有效。     

运动调控铁死亡改善帕金森病的潜在机制

帕金森病 （Parkinson’s disease, PD） 是一种以肌强直、静止性震颤及姿势障碍为主要症状的神经退行性疾病。研究表明,铁负荷增加、氧化应激和脂质过氧化在PD的发病机制中起关键作用,而铁死亡作为一种铁依赖性、脂质过氧化驱动的细胞死亡模式,可能是治疗PD的重要突破口。运动作为一种非药物干预手段,能够通过调控铁代谢相关蛋白（如铁调素、铁蛋白、铁转运蛋白）、增强抗氧化防御系统（如谷胱甘肽、谷胱甘肽过氧化物酶4、超氧化物歧化酶）、减少α突触核蛋白（α-synuclein）聚集及调节谷氨酸水平,从而抑制铁死亡的发生,保护神经元,预防和延缓PD的进展。具体而言,运动干预可通过下调二价金属离子转运体1（divalent metal transporter 1,DMT1）和上调膜铁转运蛋白l（ferroportin 1,FPN1）表达,减少细胞内铁积聚,通过增强抗氧化酶活性,降低脂质过氧化水平,通过减少α-synuclein的异常聚集,减轻其引发的氧化应激损伤,通过调节谷氨酸代谢,减轻兴奋性毒性。本文综述了铁死亡在PD中的作用机制及其与运动干预的关系,旨在为PD的预防和治疗提供新的思路和策略。     

nhe regulation and deregulation of Wnt signaling by PARK genes in health and disease

Wingless/Int （Wnt） signaling pathways are signal transduction mechanisms that have been widely studied In the field of embryogen- esis. Recent work has established a critical role for these pathways in brain development, especially of midbrain dopaminergic neu- rones, However, the fundamental importance of Wnt signaling for the normal function of mature neurones in the adult central nervous system has also lately been demonstrated by an increasing number of studies. Parkinson＇s disease （PD） is the second most prevalent neurodegenerative disease worldwide and is currently incurable. This debilitating disease is characterized by the progres- sive loss of a subset of midbrain dopaminergic neurones in the substontla nigm leadingto typical extrapyramidal motor symptoms. The aetiology of PD is poorly understood but work performed over the Last two decades has identified a growing number of genetic defects that underlie this condition. Herewe review a growing body of data connecting genes implicated in PD--most notablythe PARKgenes-- with Wnt signaling. These observations provide clues to the normal function of these proteins in healthy neurones and suggest that deregulated Wnt signaling might be a frequent pathomechanlsm leading to PD. These observations have implications for the patho- genesis and treatment of neurodegenerative diseases in general.     

PET: A biological imaging technique

Like in vivo autoradiography, PET provides a means to image and measure rates of biological processes throughout the distributed and interrelated systems of the entire living brain. In addition, both techniques can track and image the functional interactions of the brain with other systems throughout the entire body. Technological advances are yielding higher image spatial resolution and Electronic generators for automated synthesis of positron labeled compounds. The expanding number of labeled compounds (>500) is providing a growing number of biological assays (i.e., substrate metabolism, pre and post synaptic processes, enzyme activity, interaction of medical and illicit drugs with biological systems of the brain, immune system, membrane processes). Studies of normal cerebral function focus on mapping evoked responses of various components of motor, visual, somatosensory, memory and cognitive functions. Cerebral development, neuronal plasticity, and compensatory reorganization to lesions or surgery are active areas of investigation. Various types of assays have been used to identify specific biological alterations, map progression and determine therapeutic responses in a wide variety of neuropsychiatric disorders and drug abuse.Special issue dedicated to Dr. Louis Sokoloff.