首发精神分裂症患者倒背数字作业的fMEI研究

目的利用功能磁共振成像(fMRI)探讨首发精神分裂症患者倒背数字作业激发图像的特点.方法 36例符合ICD-10诊断标准的(首发)精神分裂症患者及18名健康志愿者进行以倒背数字作业(backward digit span task, BDST)作为刺激模式、采用组块(block)设计的fMRI检查,经工作站处理后获功能图像.用阳性和阴性症状量表(PANSS)评价精神分裂症患者精神症状的严重程度. 结果 (1)健康志愿者与精神分裂症患者激活脑区的范围均较广泛,健康志愿者的左侧额上回、双侧额中回、左侧额下回、左侧中央前回、左侧顶上小叶、左侧缘上回、左侧颞下回及左侧枕颞外侧回等脑区均有明显激活.两组激活的脑区在额叶、颞叶、顶叶、枕叶及扣带回的分布,以及各脑区内部分布的差异均没有显著性(P>0.05).(2)健康志愿者与精神分裂症患者激活计数左侧额上回分别为16和11,左侧额下回分别为15和12,左侧中央前回分别为16和17,左侧颞下回分别为14和12,左侧顶上小叶分别为14和14,左侧缘上回分别为14和7,左侧枕颞外侧回分别为14和7,右侧中央前回分别为13和7,右侧枕颞外侧回分别为11和8,两组上述部位激活计数的差异均有显著性(P均＜0.05).(3)健康志愿者与精神分裂症患者左侧额叶背外侧的激活平均体积分别为(362±296)个体素和(79±101)个体素,差异有非常显著性(P=0.001);右侧顶叶后下部的激活平均体积分别为(448±273)个体素和(193±236)个体素,差异有显著性(P=0.039). 结论早期精神分裂症患者可能存在工作记忆缺陷,包括激活信息的保持及执行控制过程,激活信息的保持缺陷可能与左侧额叶腹外侧及顶叶后下部的功能低下有关,而执行控制缺陷可能与左侧额叶背外侧的功能低下有关.     

偏执型精神分裂症患者Stroop操作的功能磁共振研究

目的利用功能磁共振显像(fMRI)技术探讨精神分裂症患者注意障碍的脑功能基础。方法对14例精神分裂症患者(患者组)和16名正常人(对照组)检测Stroop测验刺激下的fMRI。结果(1)激活脑区计数(个)：Stroopl刺激下,患者组左侧额下回(11/3)、左侧颞上回(6/8)、左侧颞下回(6/8)脑区激活计数均多于对照组(分别为6/10、1/15、1/15),差异有统计学意义(P＜0.05)；Stroop2刺激下,患者组左侧前扣带皮质(ACC,4/10)、右侧额中回脑区激活计数(4/10)均少于对照组(分别为12/4、14/2),差异有统计学意义(P＜0.05),患者组左额上回激活计数(9/5)多于对照组(3/ 13),差异有统计学意义(P＜0.05)。(2)激活脑区体积(体素)：Stroop1刺激下,患者组右侧前额叶背外侧区(DLPFC,256±579)、左侧ACC(18±59)激活体积小于对照组(分别为298±597、67±87),差异有统计学意义(P＜0.05)；Stroop2刺激下,患者组两侧DLPFC(分别为73±190、80±245)、左侧ACC(17±28)激活体积小于对照组(分别为425±800、414±703、76±98),差异有统计学意义(P＜0.05)。结论精神分裂症患者的注意障碍可能与前额叶、ACC、颞叶神经回路功能障碍密切相关。     

正常人词语流畅性作业的脑功能磁共振成像研究

目的 利用功能磁共振成像(fMRI)技术探讨词语流畅性作业的脑功能定位。方法对18名健康志愿者进行词语流畅性作业的fMRI检查,fMRI用梯度回波-平面回波成像序列采集数据,经工作站处理后获功能图像。结果 经Fisher精确检验法,健康志愿者的双侧额上回、双侧额中回、右侧额下回及右侧扣带回的激活脑区计数,与理想激活脑区计数的差异均无显著性(P>0.05),其余脑区激活计数的差异均有显著性(P<0.05)。结论 双侧额叶背外侧及右侧额叶腹外侧可能参与长时记忆的提取过程,其中额叶背外侧可能参与核查及管理工作,而额叶腹外侧可能参与搜寻特异目标的过程。     

戒断期海洛因依赖者额叶认知功能的功能磁共振成像研究

目的 研究戒断期海洛因依赖者(AHD)的脑认知功能.方法 采用3.0 T磁共振成像系统,对30例AHD(AHD组)和18名健康对照者(对照组)在完成Go/NoGo任务时行全脑功能磁共振成像(fMRI)扫描,记录反应时间(RT).结果 (1)RT:AHD组在完成Go/NoGo任务时的RT[(394±34)ms]长于对照组[(374±26)ms;P<0.05].(2)fMRI:对照组在完成Go/NoGo任务时,诱发激活双侧前额叶内侧回、前扣带回以及双侧额下回等脑区;AHD组全脑活动普遍低,仅有双侧额上回和左侧额中回激活.两组间比较,AHD组激活显著低于对照组的区域主要位于在双侧额内侧回、前扣带回、额下回及双侧颞叶等脑区(P<0.005).结论 戒断期海洛因依赖者反应抑制功能障碍仍然存在,促进其认知功能的恢复可能成为戒毒、抗复吸的有效策略.     

首发精神分裂症患者治疗前后脑功能磁共振成像的研究

目的 利用功能磁共振成像(fMRI)探讨首发精神分裂症患者利培酮治疗前后认知功能激发图像的特点。方法 18例首发精神分裂症患者治疗前进行倒背数字作业的fMRI检查,经利培酮[(3.8±0.9)mg/d]治疗(57±9)d后复查fMRI(16例)。用阳性和阴性症状量表(PANSS)及治疗中需处理的不良反应症状量表评价精神症状的严重程度及不良反应。结果 (1)利培酮治疗后的PANSS减分率为(50±22)％,有效率为72％。(2)治疗前倒背数字作业激活范围较广泛,包括额叶、顶叶及颞叶等脑区。(3)左侧额上回治疗前激活脑区计数为4,治疗后计数为12,治疗前后激活脑区计数的差异有非常显著性(P=0.009);左侧额叶腹外侧面治疗前激活平均体积为(15±38)个体素,治疗后激活平均体积为(67±76)个体素,治疗前后的差异有显著性(P=0.046)。结论 首发精神分裂症患者在发病初期就存在工作记忆缺陷,这种缺陷可能与左侧额上回及额下回激活低下有关,利培酮治疗可改善患者的工作记忆缺陷。     

矿难后急性重性创伤后应激障碍症状激发和创伤有关短期记忆提取的功能性磁共振成像研究

目的 探讨急性重性创伤后应激障碍(post traumatic stress disorder,PTSD)患者的脑功能及执行记忆功能时的脑反应.方法 采用功能磁共振成像技术,对经历矿难的10例急性重性PTSD患者(PTSD组)和7例非PTSD对照(非PTSD组)执行症状激发任务,并首次采用1项创伤有关的短期记忆提取任务进行记忆功能的测定.结果 症状激发试验中,PTSD组负性图片相比中性图片,左侧后扣带回、双侧尾状核和右侧丘脑等脑区激活增强,右侧扣带回和双侧额中回激活下降;PTSD组相比非PTSD组,右侧前扣带回、左侧额下回、双侧额中回及双侧颞中回等脑区激活下降,左侧海马旁回激活增高.短期记忆提取任务中,PTSD组负性图片相比中性图片,右侧后扣带回和双侧海马存在明显激活;PTSD组相比非PTSD组,右侧额下回、右侧额中回、左侧枕中回等脑区激活下降.记忆提取任务相比症状激发任务,PTSD组右侧海马旁回激活下降.结论 急性重性PTSD患者在急性期已存在部分脑区激活的下降以及记忆功能的减退.     

首发未用药精神分裂症与精神分裂症患者健康子女静息态脑功能低频振幅研究

目的探讨首发未用药精神分裂症患者和精神分裂症患者健康子女脑功能磁共振低频振幅(amplitude of low frequency fluctuation,ALFF)的共性与差异。方法应用静息态功能磁共振ALFF的方法对年龄30岁的23例首发未用药精神分裂症患者、25名精神分裂症患者健康子女以及29名健康对照进行大脑范围内ALFF值比较。结果与对照组相比,患者组和患者子女组在左侧颞下回后部、左侧海马旁回、左侧海马、右侧中央后回、双侧楔前叶的ALFF值有统计学差异(P0.05),而患者组和患者子女组间在以上脑区的ALFF值无统计学差异(P0.05);与患者子女组和对照组相比,患者组在左侧颞下回前部、左侧颞上极、双侧距状裂周围皮层的ALFF值有统计学差异(P0.05),患者子女组和对照组间在以上脑区的ALFF值无统计学差异(P0.05)。结论首发未用药精神分裂症患者以及精神分裂症患者健康子女都存在脑功能异常;左侧颞下回后部、左侧海马旁回、左侧海马、右侧中央后回、双侧楔前叶可能是与精神分裂症遗传素质性相关的脑区;左侧颞下回前部、左侧颞上极、双侧距状裂周围皮层可能是与疾病状态性相关的脑区。     

男性精神分裂症患者Stroop效应的脑功能磁共振成像研究

目的采用功能磁共振成像(fMRI)技术,探讨男性精神分裂症患者Stroop效应的行为学及脑区激活的特点。方法采用慢速事件-相关设计的Stroop-like任务,任务范式包括一致状态(CC)和不一致状态(IC)两种试验,对26例精神分裂症男性患者(患者组)和17名与患者组的年龄、受教育年限相匹配的正常人(对照组)进行fMRI检查。使用统计参数激活图(SPM2)及功能影像分析(AFNI)软件对图像进行分析。结果(1)在CC下,对照组的反应时间[(610.9±69.1)ms]短于患者组[(665.0±85.5)ms;P<0.05];在IC下,对照组的反应时间[(711.5±84.8)ms]虽短于患者组[(757.7±130.9)ms],但差异无统计学意义(P>0.05);两组IC的反应时间均长于CC(P<0.01)。两组脑激活图均未观察到IC较CC增加激活的脑区。(2)患者组表现为多个脑区的局部一致性下降,主要分布于右侧岛叶、额下回、颞下回,以及左侧扣带回前部、山顶(小脑)和额中回。结论男性精神分裂症患者的行为学存在明显的Stroop效应,而脑区激活却未见Stroop效应。     

空间记忆广度的脑功能磁共振研究

目的本实验拟通过功能磁共振研究参与正常人空间记忆广度任务的脑功能区和特点。方法10名右利手健康志愿者进行一项空间记忆广度任务作业的同时进行脑功能磁共振扫描,实验采用组块设计,实验任务与对照任务交替进行,数据采用SPM99软件进行数据分析和脑功能区定位。结果当统计阈值设定为P(0.0001时,被试者的双侧Brodmann区(Brodmann area,BA)6区(额中下回)、右BA9区(额中下回)、左额下回BA47区、双侧顶叶BA7区(楔前叶、顶上小叶)、双侧顶叶BA40区(缘上回),右枕叶BA18、19区、右海马回BA30区、左枕颞交界处BA37区、双侧顶叶中央后回BA3区、左顶叶中央后回BA2区、右中央前回BA4区及左中脑黑质、右小脑均有激活,以顶叶的激活最为显著,其次为额叶、枕叶,其中额叶的BA9区和枕叶的BA18、19区及海马回、小脑的激活有极其明显的右侧半球优势;当统计阈值设定为P(0.001时,脑激活区增加了右前扣带回BA25区,右侧额下回BA47区、左额叶BA9区,左侧枕叶BA17、18、19区及右屏状核,左丘脑侧后核。结论与空间记忆广度有关的主要脑区有BA9、6、7、40、19区和海马回、小脑。它们在进行短时空间记忆任务时所起的作用不同。通过fMRI的研究,揭示了大脑进行空间信息的处理过程。     

首发精神分裂症患者的功能磁共振初步研究

目的 利用血氧水平依赖性(blood oxygenation level-dependent,BOLD)功能磁共振成像(functional magnetic resonance imaging,fMRI)技术探讨首发精神分裂症患者治疗前后认知功能激发图像的特点。方法 13例首发精神分裂症患者入组,用利培酮或氯丙嗪治疗后9例患者复查fMRI。以词语流畅性作业(verbal fluency task,VF)作为任务,采用Block设计,用梯度回波-平面回波成像(GRE-EPI)序列采集数据,经工作站处理后获功能图像。结果 (1)VF激活受试者的额叶(前额叶)、顶叶及颞叶皮层;(2)复查的9例受试者中,7例激活增强,2例激活减弱;(3)治疗后激活增强的7例受试者的双侧额上、中、下回激活有增加趋势,而双侧颞上、中、下回激活有减少趋势(P>0.05);但左额叶背外侧面治疗后的激活明显强于治疗前(P=0.032)。结论 BOLD-fMRI可用于研究人脑的高级认知功能。首发精神分裂症患者治疗前后脑功能图像有明显变化,提示认知缺陷症状是可以治疗的。     

Treatment Considerations in Anticonvulsant Monotherapy

Summary: The long-standing practice of polypharmacy in treating epilepsy is giving way to use of monotherapy. Monotherapy can improve seizure control as well as reduce the risk of serious idiosyncratic reactions, dose-related side effects, and complex drug interactions. Monotherapy also offers improved compliance and cost-effectiveness. The basis of monotherapy is accurate diagnosis and assessment of the patient's seizure type(s), followed by selection of a single appropriate anticonvulsant drug. Many patients currently treated with multiple anticonvulsants can be successfully converted to monotherapy with a carefully monitored program in which troublesome and redundant drugs are gradually withdrawn from the therapeutic regimen.     

Dextromethorphan: Cellular Effects Reducing Neuronal Hyperactivity

Summary: Dextromethorphan is a dextrorotary morphinan without affinity for opioid receptors, commonly used as an antitussive medication. During the past 5 years, interest in the compound and its demethylated derivative, dextrorphan, has been revived because additional neuroprotective and an-tiepileptic properties were found in in vitro studies, animal experiments, and a few clinical cases. Both morphinans are able to inhibit N -methyl-D-aspartate (NMDA) receptor channels and voltage-operated calcium and sodium channels with different potencies. The inhibition of the NMDA receptor is believed to be the predominant mechanism of action responsible for the anticonvulsant and neuroprotective properties of the compounds.     

Pediatric Epilepsy Surgery

Summary: The use of implantable arrays of epidural electrodes has made it possible to carry out extraoperative electrocorticography (ECoG) and functional localization in the awake child. This has permitted cortical excisions that are determined by criteria similar to those obtained during surgical procedures performed under local anesthesia in adults. In addition, the method also permits simultaneous ECoG and video monitoring during the child's symptomatic seizures, providing additional important localizing information that is impractical to obtain in operations under local anesthesia. We report our experience with 75 children, ages 5 months to 15 years, whom we have managed with epidural electrode arrays. The method of extraoperative ECoG is described and illustrative cases are presented to demonstrate its feasibility and utility in children. In addition, we call attention to gliomas as a common cause of chronic focal seizures in children. Of 49 children undergoing resection and followed for from 1 to 14 years (mean of 5.8 years), 32 (65%) are either seizure free or have had a significant reduction in seizure frequency that has unambiguously improved their quality of life. The results are analyzed further by relating the surgical outcome to each of the pathologic entities that caused the seizures. This analysis reveals the variety of neurological conditions that commonly cause intractable focal seizure disorder in children and distinguishes those pathologic entities in which the seizure disorder is apt to respond to surgical intervention from those that will not.     

Un nouveau cadre conceptuel de travail pour une psychiatrie revisitée ? Introduction à deux articles de E. Kandel

In two articles which appeared in the American Journal of Psychiatry and that were subsequently translated for Évolution Psychiatrique, E. Kandel examines the bases for a reinterpreted psychiatry that is prepared to confront the major challenge of the 3rd millenium: that of insight into the mind and brain. This requires a major reorganization of the discipline, which involves a reinvestment of the scientific approach and a critical  assessment of the data provided by psychoanalytical psychiatry and cognitive neurosciences. Seven concepts have therefore been proposed for interactive re-examination: consciousness, the unconscious, memory, emotion, development, desire, impulse. The dynamic relations existing between genetics and the environment allow one to see how evolutions are possible from actions at different levels, both psychotherapeutic and pharmacological. Imaging and other techniques provide additional objective information to the process of human interaction which remains the basis of psychiatry. A common framework for psychiatry and the neurosciences, a reconsideration and renewal of the psychoanalytical approach are both possible and necessary.     

Opioids and the developing organism: A comprehensive bibliography, 1984–1988

A comprehensive bibliography of the literature concerned with opioids and the developing organism for 1984-1988 is presented. Utilized with companion papers (Neurosci. Biobehav. Rev. 6:439-479; 1982; 8:387-403; 1984), these articles cover the clinical and laboratory references beginning in 1875. For the years 1984, 1985, 1986, 1987, and 1988, a total of 877 citations were recorded. A series of indexes accompanies the citations in order to make the literature more accessible. These indexes are divided into clinical and laboratory topics, and subdivided into such topics as the type of opioid explored and the general area of biological interest (e.g., physiology).     

La biologie et le futur de la psychanalyse : un nouveau cadre conceptuel de travail pour une psychiatrie revisitée

The American Journal of Psychiatry has received a number of letters in response to my earlier “Framework” article (1). Some of these are reprinted elsewhere in this issue, and I have answered them briefly there. However, one issue raised by some letters deserves a more detailed answer, and that relates to whether biology is at all relevant to psychoanalysis. To my mind, this issue is so central to the future of psychoanalysis that it cannot be addressed with a brief comment. I therefore have written this article in an attempt to outline the importance of biology for the future of psychoanalysis.     

Facteurs de risque environnementaux à la schizophrénie

Schizophrenia is currently a major concern, its prevalence being estimated at around 1% and its social consequences being severe. The elucidation of the pathophysiology of the disease is difficult due to the great variability of clinical expressions, the instability of the clinical symptoms during the evolution and the absence of reliable biological markers. The existence of a familial aggregation in schizophrenia is well known, the risk of presenting the disease for first-degree relatives of patients being 5 to 10 times higher than the risk observed in the general population. The genetic component was further confirmed by twin and adoption studies. Although the concordance for the disease is higher (40 to 70%) among monozygotic twins as compared with dizygotic twins (15%) it does not reach 100%, which implies that environmental factors modulate the effects of the genotype. However, the role of these factors and especially their interaction with genetic factors remain unclear but the implications of some specific environmental factors are well documented by recent research data. The current literature on sex differences in schizophrenia is consistent. Several studies have suggested that male and female patients may differ in age at the onset and expression of clinical symptoms. Complications during pregnancy or birth-giving may increase the risk of developing schizophrenia later in life. The major complications are oxygen deprivation during pregnancy, bleeding, maternal malnutrition or infection (exposure to influenza, for example). A low birth weight is associated with an increased risk of schizophrenia. Psychoses are more common among people living in an urban environment and among those born during winter months. Schizophrenia is probably more prevalent in people who are living promiscuously, are subject to toxic abuse, poor nutrition and stress but here more precise data are needed. Moreover, immigrants have a higher risk of developing psychotic disorders. In addition, head traumas are associated with an increased risk of schizophrenia. Though they are contentious, some studies suggest that substance abuse (cannabis use in European countries) is related to the development of schizophrenia, especially in people with genetic vulnerability. Moreover, substance misuse may worsen the symptoms. If the environment is sufficiently stressful, people with a high genetic vulnerability will develop some degree of mental illness, including schizophrenia. Conversely, a less stressful or a protective environment may decrease the risk of its onset in persons with a predisposition to schizophrenia.     

Introduction: Goals

Summary: Epilepsy is characterized by recurrent seizures. Many epilepsies with focal seizures as well as convulsive generalized seizures respond satisfactorily to antiepileptic drugs (AEDs) that reduce repetitive firing (e.g., phenytoin, carbamazepine, and valproate) or that augment GABA_A-mediated inhibition (e.g., phenobarbital and benzodiazepines). A number of drugs presently under development, such as NMDA receptor antagonists, loreclezole, losigamone, meth-ysticine, and dextromethorphan, are promising in acute animal models of otherwise drug-resistant convulsant activity. As a result of recent studies in both experimental models and surgically resected human epileptic brain, the prospects for development of AEDs have significantly improved. Several new AEDs recently have reached the commercial market or are in experimental or clinical trials. A comparative presentation of the standing of the new AEDs with respect to their efficacy and side effects is necessary, but still very difficult. Because initial experience with new AEDs is restricted to populations with severe drug-resistant epilepsy, the crucial question whether potential new AEDs can alter prognosis is not yet definitively answered. There is a clear need to compare the effects of standard AEDs and new AEDs in naive patients and over longer follow-up periods. Moreover, because of the strong desire to develop antiepileptic therapy that directly treats the primary etiology of a given epileptic syndrome , or modifies the neurobiological processes that cause recurrent seizures, better experimental epilepsy models for chronic epilepsy and further clinical studies are necessary to increase the knowledge on the pathophysiology of distinct epileptic syndromes. In this respect, studies on the differences between responders and nonresponders to a given AED treatment are extremely valuable.