精神分裂症静息状态下的功能磁共振成像研究

目的：利用功能磁共振成像（fMRI）和局部一致性（regional homogeneity，ReHo）方法探测精神分裂症患者在静息状态下是否存在脑功能异常。方法：对18例精神分裂症患者和18例正常对照进行静息状态的fMRI检查，应用ReHo方法处理fMRI数据。结果：与正常人相比，精神分裂症患者静息状态下脑的BOLD信号的ReHo普遍降低（P〈0．05）。ReHo降低的脑区有双侧额叶内侧回、颞上回、颞下回、枕中回、枕下回和小脑后叶；左侧扣带回前部、海马回、颞中回、中央后回和脑桥；右侧额上回、顶上小叶、楔前叶、中央旁小叶、中央前回和小脑蚓部。结论：精神分裂症患者在静息状态下即可能存在脑功能异常，ReHo可能有助于精神分裂症静息状态的理解。     

海洛因成瘾者前额叶内侧皮质的静息状态功能连接

目的:探讨海洛因成瘾者脑默认网络静息状态功能连接的异常。方法:对正在接受美沙酮维持治疗的15例海洛因依赖者和15例健康对照进行静息状态脑功能磁共振扫描,以独立成分分析法获取每一个体的默认网络,并比较两组默认网络的功能连接差异。结果:与健康对照相比,海洛因成瘾者双侧前额叶内侧皮质、左侧颞中回和颞下回、小脑的功能连接升高。结论:前额叶内侧皮质可能是物质成瘾的关键脑区,可为成瘾的生物学诊断和靶向治疗提供线索。     

以阳性症状为主精神分裂症患者的静息态脑功能网络特征

目的:探索以阳性症状为主的精神分裂症患者的静息态脑功能网络特征。方法:纳入符合DSM-IV精神分裂症诊断标准的以阳性症状为主患者100例和70例健康成人,采用阳性和阴性症状量表(PANSS)评估患者的临床症状,并完成静息态磁共振成像扫描。通过独立成分分析(ICA)方法比较两组听觉网络、执行网络和凸显网络间的功能连接及网络内功能连接,并对两组间存在差异的脑功能连接指标与精神病性症状和认知功能得分进行相关性分析。结果:与对照组相比,患者组听觉网络与凸显网络间的功能连接增加[(0.49±0.27)vs.(0.38±0.23)],同时听觉网络与执行网络[左侧:(-0.10±0.22 vs.(0.002±0.21);右侧:(-0.05±0.24)vs.(0.05±0.21)]及凸显网络与执行网络间功能连接[(0.001±0.28)vs.(0.11±0.24)]降低。网络内功能连接分析显示,患者组听觉网络的左侧颞上回功能连接降低,以及执行网络的脑岛和顶下小叶脑区功能连接降低。相关分析发现,前凸显网络和右执行网络间的功能连接与冲动性行为呈负相关(r=-0.24,P<0.05),听觉网络和右执行...     

精神分裂症及其健康同胞额颞环路功能异常的研究

目的:研究精神分裂症(schizophrenia patients,SCZ)及其健康同胞(Healthy siblings,SIB)静息态下额颞环路的功能连接异常,为阐明额叶和颞叶在精神分裂症遗传易感性方面的重要作用提供新的证据。方法:研究入组SCZ、SIB,以及健康对照各27例。以既往研究所发现的静息态下SCZ及其SIB均有的局部脑功能活动异常的颞环路上的两个脑区为功能连接分析的感兴趣区,计算并比较各组的感兴趣区与全脑的脑区的功能连接强度的差异。结果:SCZ与其SIB都存在左侧颞中回与对侧额叶亚区(右侧眶额回和右侧额上回)、同侧颞叶其他亚区(左侧颞下回)的功能连接下降;以及左侧眶额回与对侧颞叶亚区(右侧颞中回)的功能连接下降。结论:本研究结果表明精神分裂症的遗传易感性可能不仅与额颞环路上的局部脑区功能活动异常有关,而且还与其对侧额颞通路的脑区间功能整合障碍有关。     

精神分裂症患者吸烟的静息态功能磁共振研究

目的:精神分裂症患者高吸烟率的原因尚不明确,静息态功能磁共振是一个比较好的工具来探索该现象的神经影像学机制。方法:采用局部一致性(Regional homogeneity,ReHo)的方法比较吸烟精神分裂症患者和不吸烟精神分裂症患者,以及不吸烟精神分裂症患者和正常不吸烟对照者之间的静息态功能磁共振(fMRI)图像。结果:设P0.001,与不吸烟精神分裂症患者相比,吸烟精神分裂症患者在左内侧额回ReHo值下降,左侧小脑后叶与左侧舌回ReHo值升高,且吸烟精神分裂症患者左侧小脑后叶的ReHo值与患者每日吸烟支数显著相关(r=0.635,P=0.027);与正常不吸烟对照组相比,不吸烟精神分裂症患者双侧内侧额回、右侧颞叶、左侧楔叶ReHo值升高,右侧前扣带回、双侧中央后回、双侧丘脑ReHo值下降。结论:吸烟精神分裂症患者存在左侧小脑后叶,左内侧额回与左侧舌回的局部一致性异常,此发现可能有助于我们探索精神分裂症患者人群吸烟的脑影像学机制。     

精神分裂症患者异常脑网络的fMRI研究

目的:比较正常组和精神分裂症患者组执行工作记忆任务时的脑激活差别,探讨精神分裂症患者执行功能障碍的脑机制.方法:对16例正常对照和16例精神分裂症患者进行数字3-back工作记忆任务的fMRI检查和数据分析处理.结果:患者组出现两个激活方向相反的脑区网络,与正常组相比激活降低脑区为双侧DLPFC、VLPFC、LPMA、PPC、PFC嘴侧部和额极及左侧SMA;激活增加脑区为MPFC、双侧颞叶和双侧扣带回.结论:精神分裂症患者执行功能损害有相应的病理生理学基础,是多个脑区功能受损、脑网络连接障碍而非单一脑区受损,前额叶与海马/颞叶-边缘皮层间功能连接破坏可能是其中的一个原因.     

首发精神分裂症幻听静息态脑功能连接的研究

目的:对首发精神分裂症幻听患者、非幻听患者以及正常对照的静息态功能核磁共振数据进行研究,探索首发精神分裂症幻听患者功能连接的异常模式。方法:本研究根据DSM-Ⅳ精神分裂症诊断标准,入组首发精神分裂症持续性幻听患者37例、首发精神分裂症非幻听患者59例及健康对照64例。对所有被试进行临床评估和静息态功能磁共振扫描,以初级听觉皮层和次级听觉皮层脑区为种子点构建全脑功能连接图,比较分析三组的连接差异。结果:首发精神分裂症幻听患者相对正常对照在左侧颞上回与对侧的岛叶、同侧内侧前额叶功能连接下降,左侧Heschl回(Heschl’s gyrus,HG)与对侧颞下回、同侧内侧前额叶功能连接下降,右侧HG与左侧的颞中回功能连接下降。首发精神分裂症非幻听患者虽与幻听患者并未发现功能连接显著差异,但相对于幻听组,非幻听患者组在更广泛的脑区出现了功能连接下降。结论:精神分裂症在疾病的早期阶段就出现了大脑不同脑区内的连接异常,尤其是双侧大脑间的"失连接"异常模式,进一步揭示了精神分裂症大脑整合功能的异常。     

基于局部一致性方法的广泛性焦虑障碍患者静息态功能磁共振成像

目的:探讨广泛性焦虑障碍(GAD)患者静息态局部脑功能的改变。方法:对17例GAD患者和19例性别、年龄相匹配的健康对照组进行静息态功能磁共振数据对比,运用局部一致性(Re Ho)分析方法,获得GAD患者局部一致性异常的脑区。结果:GAD患者静息态下Re Ho值升高的脑区有左侧颞中回、左侧额下回眶部、左侧背外侧额上回、右侧额中回、右侧顶下缘角回、右侧额下回三角部;Re Ho值降低的脑区有左侧楔叶、右侧舌回、右侧中央前回。以上升高或降低的Re Ho值与健康对照组相比有显著性差异(P0.05)。结论:GAD患者静息态下多个脑区Re Ho值存在异常。     

首发精神分裂症患者杏仁核静息态功能连接与情绪调节的相关性

目的:探讨首发精神分裂症患者静息状态下杏仁核的功能连接特点,及其与情绪调节的关系。方法:纳入符合ICD-10精神分裂症诊断标准的38例首发患者及年龄、性别、受教育程度匹配的45例正常对照。采用中文版精神分裂症认知功能成套测验(MCCB)中的情绪管理分测验评估被试的社会认知功能。被试均进行静息态功能磁共振成像扫描,以杏仁核为种子点进行功能连接分析,比较患者组和正常对照组之间的差异,并分析功能连接强度与情绪管理的相关性。结果:与正常对照组相比,患者组左侧杏仁核与左侧前扣带回的正性功能连接降低,与左侧枕中回和右侧颞中回正性功能连接增强,与右内侧额上回负性功能连接增强(均P 0. 005,Alpha Sim校正,体素值 25);右侧杏仁核与右侧楔前叶负性功能连接减弱(P 0. 005,Alpha Sim校正,体素值 25)。偏相关分析结果显示,患者组右侧杏仁核与右侧楔前叶的功能连接与情绪管理分测验呈负相关(r=-0. 56,P 0. 01)。结论:本研究显示静息态下首发精神分裂症患者杏仁核功能连接网络模式存在异常,其中右侧杏仁核与右侧楔前叶的负连接减弱可能与患者的情绪调节功能异常有关。     

癫痫患者默认网络的静息态功能磁共振成像研究

目的:分析癫痫患者静息态fMRI下默认网络及其潜在结构的变化.方法:对15名临床诊断为原发全身强直痉挛癫痫患者和20名正常志愿者静息态时的fMRI数据进行独立成分分析,依据空间最佳匹配原则挑选独立成分,研究正常被试和癫痫患者的默认网络差异,并选定默认网络中11个脑区构建功能连接网络,运用图论和聚类方法探讨其潜在结构的改变.结果:与正常对照组相比,患者组默认网络的脑区激活普遍下降,功能连接网络发生明显变化,且整个网络呈现出混乱的层次化结构.结论:静息态下癫痫患者的默认网络及潜在的层次化结构发生异常.     

Analysis of the polymorphic (GT)(n) repeat at the dopamine beta-hydroxylase gene in Spanish patients affected by schizophrenia

The presence of a polymorphic (GT)(n) repeat, a microsatellite repeat, at the human dopamine beta-hydroxylase (DBH) gene had been previously investigated in healthy people and in schizophrenic patients. The different DBH genotypes had been found to be associated to different DBH biochemical function, but no differences were found in the allelic and genotype frequencies between schizophrenic and control groups. To further clarify the potential involvement of the variation at the DBH gene in schizophrenia we have studied the DBH (GT)(n) repeat in a sample of 47 Spanish schizophrenic patients, in their healthy relatives (n = 72), and in a control population (n = 74). We have been able to identify five different variants of the DBH gene (A1, A2, A3, A4, A5) in the different groups. Subsequent statistical analysis revealed that the genotypes as well as the allele frequencies did not differ significantly among schizophrenic patients and the control population. Interestingly, the allelic variant A2 and the genotype A4/A2 were significantly more frequent in schizophrenic patients as compared with their healthy relatives. However, the association of the A2 allele with schizophrenia was not supported by the haplotype relative risk analysis of transmitted versus nontransmitted alleles. Therefore, although it will be important to extend the present analysis in a larger sample of schizophrenic patients and controls, our results suggest that the (GT)(n) does not seem to play a major role in the genetics of schizophrenia at least in this group of Spanish schizophrenic patients. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:88-92, 2000.     

Idiopathic congenital central hypoventilation syndrome: the next generation

In the present study, we sought to identify genetic variation in the metabotropic glutamate receptor 3 (GRM3) gene, which has been mapped to chromosome 7q21.1-q21.2 [Scherer et al., 1996] and might contribute to genetic predisposition to schizophrenia and/or bipolar affective disorder. Using single-strand conformation analysis (SSCA), we screened the complete coding sequence as well as adjacent splice sites of the GRM3 gene in a sample of 46 bipolar affective and 46 schizophrenic patients. We detected three sequence variants: a rare C/T substitution at nucleotide position +885 (T209T), a C/T substitution at nucleotide position +2130 (Y624Y), and a more common C/T substitution at nucleotide position +1131 (A291A). The occurrence of the +1131C/T variant was investigated in a sample of bipolar affective patients (n=283), schizophrenic patients (n=265), and ethnically matched controls (n=227). We observed a significant overrepresentation of the +1131T allele in schizophrenic patients when compared to controls (P=0.0022). This finding was followed up in an independent sample of schizophrenic patients (n=288) and controls (n=162) and 128 schizophrenic trios but could not be confirmed. It is therefore unlikely that this variant plays a major role in predisposing to schizophrenia and/or bipolar affective disorder at least in the German population.     

Subjective and physiological responses to emotion-eliciting pictures in male schizophrenic patients.

Several studies have shown that schizophrenic patients have difficulties in their ability to recognize emotional facial expressions, whereas other research indicated that they subjectively report the same emotional experience as healthy controls. The purpose of this study was to investigate whether the physiological responses that accompany emotions differ between schizophrenic patients and controls, which would suggest a different basic emotional processing mechanism in these patients. We presented 40 emotion-eliciting pictures to male patients (n=26) and controls (n=21), while measuring heart rate (HR), breathing rate (BR), skin conductance response (SCR) and systolic blood pressure (SBP). Each subject rated each picture for its degree of valence and arousal. Mixed-effects regression models were used to investigate the relationships between the subjective ratings and the physiological responses. In both groups, BR and SCR increased with increasing arousal ratings, suggesting sympathetic activation. The SBP of both groups increased with increases in both the valence and the arousal ratings. However, whereas the patients' HR first decreased with decreasing pleasure ratings and subsequently increased with higher arousal and valence ratings, the HR in the control group was influenced by a complex interaction between valence and arousal ratings. Thus, the schizophrenic patients showed similar relationships between subjective ratings and SCR, BR, and SBP, but a different relationship between subjective ratings and HR compared with the healthy controls.     

The T393C polymorphism of the GNAS1 gene is associated with deficit schizophrenia in an Italian population sample

Programmed cell death and alterations in intracellular G-protein signaling may be involved in the pathophysiology of schizophrenia. The Galphas subunit of heterotrimeric G-proteins, encoded by the gene GNAS1, may play a role in both of these processes. Additionally, transgenic mice expressing a constitutively active form of Galphas provide a reliable model of certain endophenotypes of schizophrenia. To investigate whether the functional single nucleotide polymorphism T393C in GNAS1 gene could affect risk of schizophrenia, we examined its distribution in Italian subjects with (n=383) and without (n=400) schizophrenia. We also evaluated whether a specific association could exist between the deficit (n=108) and nondeficit (n=275) forms of the disorder. The alleles and genotypes frequency in the entire cohort of schizophrenic patients did not differ from that of controls. However, the frequency of the homozygous 393TT genotype was significantly higher in deficit schizophrenic patients (37.1%) compared to both nondeficit schizophrenic (22.5%, p=0.011) and controls (22.8%, p=0.015). This association with deficit schizophrenia persisted even after allowance for potential confounders [adjusted odds ratio (OR) for deficit schizophrenia: 2.06 (95% confidence interval (CI): 1.21-3.47), p=0.007]. Altogether, our data suggest that the GNAS1 T393C status could influence susceptibility for deficit schizophrenia in Italian subjects.     

重症肌无力患者外周血中CD4~+CD25~+调节性T细胞的变化及意义

研究CD4 + CD2 5 + 调节性T细胞在重症肌无力 (MG )发病中的作用。本文采用三色流式细胞术对 2 9例MG患者和 2 3例健康对照者外周血中CD4 + CD2 5 + T细胞 (CD3+ CD4 + CD2 5 + )的百分率进行测定。结果显示病情未能很好控制的MG患者外周血CD4 + CD2 5 + T细胞比率略低于健康对照组 (分别为 3 79%± 1 4 0 %、 4 5 3%± 0 96 % ,P =0 12 ) ,病情稳定或缓解的MG患者CD4 + CD2 5 + T细胞比率 (8 4 5 %± 1 96 % )显著高于健康对照组 (P =0 0 0 0 1) ;胸腺切除的MG患者CD4 + CD2 5 + T细胞比率 (8 4 4 %± 2 39% )显著高于非胸腺切除的MG患者 (5 88%± 2 89% ,P =0 0 38)和健康对照组 (4 5 3%± 0 96 % ,P =0 0 0 3)。提示MG患者外周血中存在异常比例的CD4 + CD2 5 + 调节性T细胞 ,可能参与疾病的发生与发展。     

正常人和精神分裂症患者脑灰质体积分析的性别效应

目的:通过比较男性和女性正常人、男性和女性精神分裂症患者之间的脑灰质体积差异,探讨脑结构分析中的性别效应。方法:采集60例正常人(30例男性)和96例精神分裂症患者(48例男性)的高分辨率三维脑结构磁共振图像,运用基于体素的形态测量法(VBM)进行分析,获得每一个体的脑灰质体积图像。采用两样本t检验分别比较男性和女性正常人,男性和女性精神分裂症患者之间的脑灰质体积差异。结果:与女性正常人相比,男性正常人左侧的颞中回和额中回、右侧的边缘叶和颞中回的灰质体积较大(P<0.001),而左侧尾状核和右侧海马的灰质体积较小(P<0.001)。与女性精神分裂症患者相比,男性患者双侧的颞下回和海马、左侧的颞上回和颞中回的灰质体积较大(P<0.001),而未发现灰质体积较小的脑区。结论:性别效应是影响正常人或精神分裂症患者脑结构分析的重要因素。     

Dissociation between visual line bisection and mental number line bisection in schizophrenia

Many studies of hemispatial neglect patients have indicated that spatial attention processes operate similarly in visual space and number space. However, some studies have indicated a dissociation of processing between visual line bisection and mental number bisection. A number of investigations have suggested that schizophrenic patients show a mild right pseudo-neglect on visual line bisection tasks. The present study was designed to determine if a functional link exists between performance of visual line and number line bisection in schizophrenic patients. Groups of 40 schizophrenic patients and 40 controls performed each bisection task. In the visual line bisection task, schizophrenic patients showed a significant leftward bias relative to the healthy controls for 9 different line lengths. No significant difference in bias was found between the 2 groups on the mental line bisection task. These results indicated that schizophrenic patients may exhibit attention deficit with respect to visual space but not number space, suggestive of the dissociation of processing between visual line bisection and mental number line bisection. These results provide more insight into the correlation between the visual line and number bisection tasks in schizophrenic patients.     

偏执型精神分裂症外周血IL-1β、TNF-α和酪氨酸羟化酶的mRNA表达水平

目的检测偏执型精神分裂症患者白介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)和酪氨酸羟化酶(TH)的基因表达水平,探讨偏执型精神分裂症的外周神经免疫机制.方法采用RT-PCR和半定量技术,分别检测39例偏执型精神分裂症患者和30例正常对照外周血单个核细胞IL-1β、TNF-α和TH的基因表达水平.结果显示病例组的IL-1β、TNF-α、TH基因表达水平均显著高于正常对照组(P＜0.01).且对照组IL-1β和TNF-α基因表达水平显著相关(r=0.847,P＜0.01);IL-1β和TH基因表达水平相关性较为显著(r=0.666,P＜0.01).病例组只有IL-1β和TNF-α基因表达水平表现为显著的相关(r=0.942,P＜0.01).结论偏执型精神分裂症患者可能存在致炎性细胞因子和儿茶酚胺类神经递质的过度表达;儿茶酚胺类神经递质和致炎性细胞因子的基因表达之间可能具有一种交互机制,而偏执型精神分裂症患者的这种交互机制发生了紊乱.     

13C-methionine breath test detects distinct hepatic mitochondrial dysfunction in HIV-infected patients with normal serum lactate

OBJECTIVE: To assess mitochondrial respiratory chain dysfunction in different treatment groups of HIV-infected patients with normal serum lactate by measuring hepatic mitochondrial decarboxylation capacity by the C-methionine breath test (MeBT) and to correlate MeBT results with mitochondrial DNA (mtDNA) content in peripheral blood mononuclear cells (PBMCs). METHODS: Four groups were studied: HIV-negative controls (n = 10), treatment-naive patients (n = 15), antiretroviral therapy (ART)-treated patients with asymptomatic disease (n = 15), and patients with long-term treatment and clinical evidence of lipoatrophy (n = 15). After oral administration of C-methionine, CO2 exhalation was determined by infrared spectroscopy. MtDNA content in PBMCs was assessed by real-time polymerase chain reaction quantification. RESULTS: CO2 exhalation in lipoatrophic patients and therapy-naive patients was distinctly decreased when compared with that in healthy controls and asymptomatic patients (P < 0.001). The functional mitochondrial impairment in lipoatrophic patients was associated with a 47% decline in mtDNA content. MeBT results and mtDNA were significantly correlated in ART-treated patients (r = 0.77, P < 0.0001). CONCLUSIONS: MeBT is a simple noninvasive method to detect mitochondrial dysfunction in HIV-infected patients that correlates with mtDNA depletion in PBMCs of ART-treated individuals. Decreased hepatic methionine metabolism in therapy-naive patients may reflect the functional relevance of viral-mediated mitochondrial toxicity.     

Aberrant brain activation following motor skill learning in schizophrenic patients as shown by functional magnetic resonance imaging

BACKGROUND: Motor skill learning may be impaired in schizophrenia. While functional brain imaging studies have shown reduced activation during motor task performance in schizophrenic patients, brain activity changes with motor skill learning in these patients have not been studied by functional imaging. METHODS: A sequential complex motor task involving the right hand was performed by nine medicated schizophrenic patients and 10 age-matched healthy controls. Functional magnetic resonance images were obtained using a gradient echo, echoplanar imaging (EPI) pulse sequence before and after 1 week of training in performing the task. RESULTS: Bilaterally, patients showed significantly less blood oxygenation level-dependent (BOLD) signal response in the premotor area (PMA) before beginning motor training than controls. BOLD signal response increased in the left PMA of schizophrenic patients after 1 week of motor training; in contrast, the signal decreased in the left PMA of control subjects. Training effects concerning the number of finger movement sequences achieved did not differ between groups. Daily neuroleptic dose did not significantly affect changes with training in BOLD signal response in the PMA. CONCLUSIONS: These preliminary results suggest that schizophrenic patients have dysfunction of neural networks in areas including the PMA that are involved in executing a complex motor task. In terms of brain activity, motor learning may be less efficient or slower in the patients than in healthy subjects.