齐拉西酮对精神分裂症患者执行功能障碍的影响

认知功能损害是精神分裂症的核心症状之一，其中执行功能障碍是最主要的认知损害。研究显示齐拉西酮对精神分裂症的认知功能有改善作用。本文探讨齐拉西酮对精神分裂症执行功能障碍的疗效，并与氯氮平治疗精神分裂症患者进行对照研究。     

老年慢性精神分裂症与Alzheimer病的认知功能筛查结果比较

应用认知功能筛查量表（ＣＡＳＩ）评定４１名正常老人、８５名老年慢性精神分裂症与３５名Ａｌｚｈｅｉｍｅｒ病患者，结果显示老年慢性精神分裂症患者中约一半有认知功能缺损。认知相对保存的分裂症患者的ＣＡＳＩ总分、因子分较正常老人明显减低；认知损害的分裂症患者的认知损害模式与Ａｌｚｈｅｉｍｅｒ病的损害不同。结论：老年慢性精神分裂症患者的认知损害可能具有独特的模式，不同认知结局的精神分裂症可能存在异源性病因。     

精神分裂症患者认知功能评估方法的研究进展

认知功能损害是精神分裂患者三大核心症状之一,并且在精神分裂症患者中长期、广泛存在。精神分裂症患者认知损害主要体现在注意、记忆和执行功能等方面。改善精神分裂症患者认知功能与其社会功能恢复和生活质量的提高密切相关。然而精神分裂症患者认知功能的评估难度大、耗时长,且方法不尽相同。为了能更好地认识、评估精神分裂症患者认知功能,本文通过检索国内外文献,综述了评估精神分裂症患者认知功能几种常用方法,为更好地认识、评估精神分裂症患者的认知功能提供参考。     

阴性精神分裂症患者局部脑血流与威斯康星卡片分类测验的相关分析

目的：为探讨阴性精神分裂症患者脑结构与认知功能缺陷的关系。方法：运用单光子发射计算机断层扫描（ＳＰＥＣＴ），测定了１２例阴性精神分裂症患者在安静状态与威斯康星卡片分类测验的负荷状态下的局部脑血流。结果：在安静状态下阴性精神分裂症病人的脑局部放射性分布是对称的，但在威斯康星卡片分类测验的刺激状态下左、右侧额叶的局部脑放射性计数是不对称的。结论：提示精神分裂症的阴性症状与左侧额叶的功能状态有关。     

精神分裂症患者杏仁核的结构及功能磁共振成像研究(综述)

杏仁核作为边缘系统中参与情绪处理的重要脑区,其功能的异常与精神分裂症的情绪认知及加工功能缺损相关。本文回顾了精神分裂症患者杏仁核结构与功能磁共振成像的研究,分析了二者的变化与精神分裂症患者临床症状的关联性,并进一步探讨了杏仁核相关脑网络的功能异常与精神分裂症患者情绪认知异常的关系。未来的研究可以基于统一的实验范式,分析精神分裂症患者治疗前后杏仁核结构及功能磁共振成像的动态变化,将有助于寻找与疾病诊断和疗效评价、预测有关的影像学指标。     

认知负载状态下的精神分裂症患者脑电图特异性研究

认知功能损害是精神分裂症的三大原发症状之一,在疾病早期发现和高危人群风险预警等方面具有重要价值。为了研究精神分裂症患者在认知负载状态下的脑电图特异性,本试验收集17例精神分裂症患者和19例健康受试者的脑电信号作为对照,基于小波变换提取各频段信号,计算非线性动力学及脑功能网络属性等特征,并利用机器学习算法将两类人群进行自动分类分析。试验结果表明,两组受试者在认知负载状态下,Fp1和Fp2导联在α、β、θ、γ这4个频带的关联维数和样本熵的差异均具有统计学意义,提示大脑额叶功能损伤是精神分裂症认知功能损害的重要原因。进一步基于机器学习的自动分类分析结果表明,将非线性动力学与脑功能网络属性相结合作为分类器的输入特征,所得分类效果最优,其结果显示准确率为76.77%、敏感度为72.09%、特异性为80.36%。本研究结果表明,脑电信号的非线性动力学和脑功能网络属性等特征,或可作为精神分裂症早期筛查和辅助诊断的潜在生物标记物。     

阴性精神分裂症患者局部脑血流与威斯康星卡片分类测验的…

目的：为探讨阴性精神分裂症患者脑结构与认知功能缺争的关系，方法，运用单光子发射计算机断层扫描（ＳＰＥＣＴ）测定了１２例阴性精神分裂症患者有在安静状态下与威斯康星卡片分类测验的负荷状态下的局部血流，结果，在安静状态下阴性精神分裂症病人的脑局部放射性分布是对称的，但在威斯星卡片分类测验的刺激状态下左，右侧额叶的局部放射性计数是不对称的。结论：提示精神分裂症的阴性症状与左侧额叶的功能状态有关。     

精神分裂症病因新探

基于分裂症神经认知功能损害的诸多事实，提出精神分裂症的海马应激损害学说，为分裂症病因研究提出新的思路，即主要以海马等脑损害为突破口，探讨分裂症的可能原因。     

精神分裂症患者认知功能损伤的神经生物学基础和电生理表现

精神分裂症患者存在严重的认知功能损伤，认知功能损伤的重要神经生物学基础是患者脑内神经递质水平异常，这会导致患者出现异常神经元电活动，脑电图指标可以客观、定量反映神经递质导致的异常神经元电活动。本文主要对国内外精神分裂症患者认知功能损伤的神经生物学和电生理学等研究情况进行综述，回顾了认知功能损伤相关神经递质的生物学机制，梳理了与之相关的异常神经生物电指标，为精神分裂症的发病原理和辅助诊断提供相应参考。未来的研究应更多关注疾病的致病基因、神经影像学等生物学标记物，建立精神分裂症辅助诊断的指标体系。     

女性精神分裂症患者认知功能损害危险因素

目的探讨女性精神分裂症患者认知功能损害的危险因素,提供治疗认知功能损害的依据。方法采用自编调查表、阳性与阴性症状量表(PANSS)、简易智能精神状态量表(MMSE)对100例女性精神分裂症患者调查,认知功能损害危险因素采用Logistic回归分析。结果认知功能损害发生率为72%,阴性症状是认知功能损害的危险因素(B=0.151,Exp(B)=1.163),文化水平是认知功能损害的保护因素(B=-0.282,Exp(B)=0.754)。结论阴性症状越重认知功能损害危险度越高,文化水平越高认知功能损害危险度越低。     

The spectrum of structural brain changes in schizophrenia: age of onset as a predictor of cognitive and clinical impairments and their cerebral correlates

A range of cerebral structures was assessed in a series of 172 CT scans of groups of psychiatric patients (including 101 in-patients with chronic schizophrenia) and related to assessments of clinical state and psychological function. Ventricular indices were increased in patients with schizophrenia by comparison with patients with other psychiatric disorders: brain area, which is modestly positively correlated with ventricular indices, was significantly (P less than 0.01) reduced in patients with schizophrenia. Among in-patients with chronic schizophrenia, measures of increased ventricular size were significantly associated with impaired social behaviour and with movement disorder. Memory for famous names in the distant past (a test of remote memory) was the only psychological test which showed significant associations with indices of ventricular size; this suggests that ventricular enlargement and its psychological sequelae occur relatively early in the disease process. Dichotomization of the sample of schizophrenic patients around the mean age of onset revealed that a range of clinical and psychological functions are significantly more abnormal in those with an early age of onset than in those in whom the onset was later. Early onset cases also perform less well academically and occupationally before illness onset. Within the early onset group some significant correlations between cognitive function and brain area were seen. The findings suggest that: (i) some at least of the structural changes in schizophrenia arise at a time when the brain is still developing; and (ii) age of onset is an important determinant of social and intellectual impairment and is relevant to the relationship between brain structure and cognitive deficits.     

Gyrification and neural connectivity in schizophrenia

There is emerging evidence for a connection between the surface morphology of the brain and its underlying connectivity. The foundation for this relationship is thought to be established during brain development through the shaping influences of tension exerted by viscoelastic nerve fibers. The tension-based morphogenesis results in compact wiring that enhances efficient neural processing. Individuals with schizophrenia present with multiple symptoms that can include impaired thought, action, perception, and cognition. The global nature of these symptoms has led researchers to explore a more global disruption of neuronal connectivity as a theory to explain the vast array of clinical and cognitive symptoms in schizophrenia. If cerebral function and form are linked through the organization of neural connectivity, then a disruption in neural connectivity may also alter the surface morphology of the brain. This paper reviews developmental theories of gyrification and the potential interaction between gyrification and neuronal connectivity. Studies of gyrification abnormalities in children, adolescents, and adults with schizophrenia demonstrate a relationship between disrupted function and altered morphology in the surface patterns of the cerebral cortex. This altered form may provide helpful clues in understanding the neurobiological abnormalities associated with schizophrenia.     

6R-l-erythro-5,6,7,8-tetrahydrobiopterin (BH4): A potential treatment for all symptom domains of schizophrenia

Current psychopharmacological treatment of schizophrenia is suboptimal and the available antipsychotic medications have little or no effect on negative and cognitive symptom domains of the disorder. 6R-l-erythro-5,6,7,8-tetrahydrobiopterin (BH4) is a cofactor involved in the synthesis of dopamine, serotonin and nitric oxide which have all been implicated in the pathophysiology of schizophrenia. BH4 may potentiate dopaminergic neurotransmission via mechanisms independent of dopamine biosynthesis. BH4 may also potentiate NMDA neurotransmission through its cofactor effect on nitric oxide synthase (NOS). The hypothesis being advanced is that BH4 will be effective in treating all symptom domains of schizophrenia. The hypothesis is based on the findings of: (1) reduced BH4 levels in schizophrenia patients; (2) negative and cognitive symptoms of schizophrenia are related to reduced dopamine neurotransmission in some parts of the brain and BH4 may correct this abnormality by potentiating dopaminergic neurotransmission in these brain regions; (3) there is reduced cellular expression of neuronal NOS in certain brain regions of schizophrenia patients relative to healthy controls, an abnormality which may be corrected via BH4 cofactor effect on NOS; (4) there is increased neuroinflammation in schizophrenia, and BH4 may be anti-inflammatory; (5) schizophrenia is associated with hyperphenyalaninemia (which maybe neurotoxic) and BH4 has clinical utility in normalizing phenylalanine levels. Confirming this hypothesis would advance the knowledge of the pathophysiology of schizophrenia and also meet a significant treatment need in the overall management of this severe and chronic illness.     

Loss of function of glial gap junctions may cause severe cognitive impairments in schizophrenia

A generalized cognitive deficit is at the core of schizophrenia. It is hypothesized that a loss of function of glial gap junctions may cause severe cognitive impairment in schizophrenia. Glial gap junctions are electrical channels that may register the neuronal activation frequencies of glial–neuronal compartments by generating gap junction plaques. The various proteins (connexins) of gap junctions may be capable to differentiate between the operation qualities of the cognate synapses defined by the neurotransmitter types. Thus, the brain is capable of distinguishing between different cognitive qualities (domains or categories). If the function of glial gap junction proteins is lost, the brain is incapable to distinguish between same and different qualities of information processing. Dependent on the brain regions affected, this disorder may be responsible for severe cognitive impairment in schizophrenia. Finally, general approaches for testing the hypothesis are outlined.     

Brain maturational processes and delayed onset in schizophrenia.

The central feature of schizophrenia is its onset in adolescence. Although this clinical observation is consistent with the view that schizophrenia may be a neurodevelopmental disorder, debate has focused on when the proposed brain maturational deviations may begin and what might be the nature of such defective development. Conflicting models of this illness (e.g., the early and late neurodevelopmental models) have been proposed. In this paper, we will first review concepts from basic developmental neurobiology pertinent to these issues; we then summarize aspects of the neurobiology of schizophrenia that have a particular bearing on the adolescent onset of this illness. We propose that the schizophrenic syndrome may result from early brain adversity and late maturational processes of brain development interacting with adverse humoral, biochemical, and psychosocial factors during adolescence and early adulthood. The onset of schizophrenia in adolescence may be related to the "plasticity switch" secondary to the peripubertal brain maturational changes, perhaps involving an alteration in glutamate receptor function. This loss of plasticity could result in social and nonsocial cognitive deficits that are central to the pathophysiology of schizophrenia; the vulnerable person may therefore utilize prepubertal processing styles that are insufficient to the adaptive and "gistful" abstraction requirements of adult cognition. Schizophrenia onset might occur in the context of psychosocial developmental challenges to a delayed social cognitive capacity among neurodevelopmentally compromised individuals. We review therapeutic implications as well as testable predictions generated by this model, and discuss research strategies that might further our understanding of the brain maturational abnormalities in schizophrenia.     

动态因果模型在脑网络研究中的应用进展

大脑各功能区之间的有效连接是脑科学研究领域的一个重要内容.研究在不同情形下相关脑区之间有效连接所构成的大脑网络,对于全面理解大脑的功能机制,治疗各种与大脑相关疾病,开发脑功能具有重要意义.动态因果模型是一种分析大脑有效连接的优势方法.结合功能性磁共振成像、脑电、近红外脑功能成像等3种检测技术,综述动态因果模型的相关研究...     

认知控制任务下精神分裂症患者健康亲属大脑激活模式的元分析

目的:探究认知控制任务下,精神分裂症患者健康亲属的大脑激活模式。方法:首先对近年来利用认知控制任务探究精神分裂症患者激活模式的文献进行整理;而后对各项研究的激活坐标进行提取和空间转换;最后利用似然估计的方法对提取的坐标进行系统的定量分析。结果:研究发现,与正常对照组相比,精神分裂症患者的健康亲属的左侧脑岛(似然估计值ALE=0.012,峰值坐标:x=-40,y=18,z=0)和左侧扣带回(似然估计值ALE=0.011,峰值坐标:x=-2,y=10,z=38)激活水平显著降低,左侧额上回(似然估计值ALE=0.013,峰值坐标:x=0,y=8,z=50)和左侧中央前回(似然估计值ALE=0.001,峰值坐标:x=-38,y=2,z=36)激活水平显著地增高(P0.05)。结论:与认知控制有关的大脑激活模式可能可以作为精神分裂症研究的一个内观遗传表型。     

Glucagon-like peptide-1 analogues against antipsychotic-induced weight gain: potential physiological benefits

ABSTRACT: BACKGROUND: Antipsychotic-induced weight gain constitutes a major unresolved clinical problem which may ultimately be associated with reducing life expectancy by 25 years. Overweight is associated with brain deterioration, cognitive decline and poor quality of life, factors which are already compromised in normal weight patients with schizophrenia. Here we outline the current strategies against antipsychotic-induced weight gain, and we describe peripheral and cerebral effects of the gut hormone glucagon-like peptide-1 (GLP-1). Moreover, we account for similarities in brain changes between schizophrenia and overweight patients. DISCUSSION: Current interventions against antipsychotic-induced weight gain do not facilitate a substantial and lasting weight loss. GLP-1 analogues used in the treatment of type 2 diabetes are associated with significant and sustained weight loss in overweight patients. Potential effects of treating schizophrenia patients with antipsychotic-induced weight gain with GLP-1 analogues are discussed. CONCLUSIONS: We propose that adjunctive treatment with GLP-1 analogues may constitute a new avenue to treat and prevent metabolic and cerebral deficiencies in schizophrenia patients with antipsychotic-induced weight gain. Clinical research to support this idea is highly warranted.     

Alpha7 nicotinic cholinergic neuromodulation may reconcile multiple neurotransmitter hypotheses of schizophrenia

The long prevailing hypothesis of schizophrenia pathogenesis implicates dopaminergic systems in the mesolimbic pathways as responsible for the positive symptoms of schizophrenia (hallucinations and delusions) and those in the mesocortical pathway as contributing to the negative symptoms (e.g., social disconnection, flattened affect and anhedonia). Several challenges to the dopamine hypothesis and the proposal of an alternative hypothesis implicating glutamate have provided additional support for the development of non-dopaminergic drugs for the management of schizophrenia symptomatology. Furthermore, preclinical and clinical evidence of alpha7 neuronal nicotinic acetylcholine receptor-mediated benefits in the triad of positive symptoms, negative symptoms and cognitive dysfunction in schizophrenia, as well as the genetic linkage of this receptor to the disease, have added another level of complexity. Thus schizophrenia is increasingly believed to involve multi-neurotransmitter deficits, all of which may contribute to altered dopaminergic tone in the mesolimbic, mesocortical and other areas of the brain. In this paper we provide a model that reconciles the dopamine, glutamate and alpha7 cholinergic etiopathogenesis and is consistent with the clinical benefit derived from therapies targeted to these individual pathways.     

Optogenetic neuronal control in schizophrenia

Schizophrenia is a serious mental disorder characterized by a heterogeneous spectrum of clinical manifestations. Schizophrenia is basically incurable. The discovery of antipsychotic medications in the late 1940s has helped control some of the symptoms but has not reversed the course of the disorder and has had limited effect on the debilitating symptoms of the illness. In recent years brain stimulation technologies have emerged in the bio-scientific scenery. Deep brain stimulation now plays an important role in the treatment of many neurological disorders, and seems promising in treating depression. Optogenetics is a new technology that offers control over neuronal activity by turning on and off distinct neuronal populations. It has a great advantage over previous brain stimulation technologies in that it is accurate and specific to the neurons intended for activation and control. There is no evidence that brain stimulation has been investigated in schizophrenia patients. This possibility was discussed in a single commentary that proposed the hippocampus and nucleus accumbence as targets for DBS in schizophrenia, however it was emphasized that the neurophysiology and neuroanatomy of schizophrenia have not been elucidated to the extent that brain stimulation can be planned. In light of new optogenetic technology time is ripe to seriously consider optional targets of intervention in the brain of schizophrenia patients. Any such target should involve neuronal circuits (1) known to be relevant for schizophrenia, (2) involved in cognitive and brain functions that are disturbed in schizophrenia, and (3) relevant to alleged neuronal network mechanisms that are presumably damaged or malfunctioning in schizophrenia. This paper reviews the relevant literature and proposes that optogenetic interventions in schizophrenia should begin in the prefrontal cortex and the Globus-Pallidus Subthalamic nuclei systems. In the protocol for the prefrontal cortex, wide-arbore and chandelier inhibitory interneurons should be targets for optogenetic intervention and in the Globus-Pallidus Subthalamic nuclei the fast spiking neurons should be targets for optogenetic intervention. These subsystems are critical modulators of neural complexity which is directly relevant to connectivity organization in the brain. Schizophrenia is described as a disturbance of connectivity organization in the brain treatable by the relevant optogenetic interventions promoted in this paper.