西酞普兰与氯米帕明治疗强迫症对照研究

目的：比较西酞普兰与氯米帕明治疗强迫症的疗效和不良反应。方法：以西酞普兰和氯米帕明治疗强迫症各30例,疗程8周。应用Yale—Brown强迫症量表（Y—BOCS）、汉密尔顿抑郁量表（HAUD）及汉密尔顿焦虑量表（HAMA）评定疗效。结果：西酞普兰组与氯米帕明组治疗后Y-BOCS、HAMD、HAMA分值均显著下降,两组间差异无显著性。西酞普兰组不良反应明显少于氯米帕明组。结论：西酞普兰治疗强迫症疗效与氯米帕明相仿,不良反应较轻,值得推广。     

Brain structural abnormalities in psychotropic drug-naive pediatric patients with obsessive-compulsive disorder

OBJECTIVE: The authors investigated structural abnormalities in brain regions comprising cortical-striatal-thalamic-cortical loops in pediatric patients with obsessive-compulsive disorder (OCD). METHOD: Volumes of the caudate nucleus, putamen, and globus pallidus and gray and white matter volumes of the anterior cingulate gyrus and superior frontal gyrus were computed from contiguous 1.5-mm magnetic resonance images from 23 psychotropic drug-naive pediatric patients with OCD (seven male patients and 16 female patients) and 27 healthy volunteers (12 male subjects and 15 female subjects). RESULTS: Patients had smaller globus pallidus volumes than healthy volunteers, but the two groups did not differ in volumes of the caudate nucleus, putamen, or frontal white matter regions. Compared to healthy volunteers, patients had more total gray matter in the anterior cingulate gyrus but not the superior frontal gyrus. Total anterior cingulate gyrus volume correlated significantly and positively with globus pallidus volume in the healthy volunteers but not in patients. CONCLUSIONS: These findings provide evidence of smaller globus pallidus volume in patients with OCD without the potentially confounding effects of prior psychotropic drug exposure. Volumetric abnormalities in the anterior cingulate gyrus appear specific to the gray matter in OCD, at least at the gross anatomic level, and are consistent with findings of functional neuroimaging studies that have reported anterior cingulate hypermetabolism in the disorder.     

Diffuse metabolic changes in the brain of patients with familial amyloid polyneuropathy. A proton MRSI study

OBJECTIVES: To assess brain metabolic abnormalities in patients with familial amyloid polyneuropathy (FAP) due to the transthyretin (TTR) gene mutations. BACKGROUND: The TTR-FAP has variable phenotypic expression, which includes abnormalities of the central nervous system (CNS). Several conventional MRI studies have shown brain abnormalities, probably secondary to amyloid accumulation in leptomeningeal and subarachnoid vessels. However, TTR-related amyloid deposits do not seem to significantly affect the brain parenchyma and a prominent CNS impairment is considered to be rare in TTR amyloidosis. METHODS: We performed proton MR spectroscopic imaging (1H-MRSI) in the central brain of four unrelated TTR-FAP patients with either minimal or no signs of neurological involvement and eight age- and sex-matched normal controls (NC). Metabolic changes were assessed in the entire volume of interest (VOI) and in the frontal, periventricular and posterior white matter (WM). RESULTS: Conventional MRI was normal in 2 patients and showed minimal WM lesions in the remaining 2 patients. 1H-MRSI showed N-acetylaspartate to creatine ratio (NAA/Cr) decreases in the central brain VOI in all TTR-FAP patients (p < 0.005). These NAA/Cr decreases were homogeneous in all WM regions (p < 0.05 for all). CONCLUSIONS: 1H-MRSI findings suggest that diffuse metabolic changes, probably related to axonal damage, are present in brains of TTR-FAP patients even when they have no or minimal clinical and MRI signs of CNS involvement. The mechanism leading to sub-clinical metabolic brain changes needs to be identified.     

Functional MRI study of brain activation alterations in patients with obsessive-compulsive disorder after symptom improvement

Dysfunction of the frontal-subcortical circuits has been the most common finding in the pathophysiology of obsessive-compulsive disorder (OCD), and recent neuropsychological studies have shown cognitive impairments in OCD. To clarify the pathophysiology of OCD without the confounding effects of medication, we investigated the alterations of brain function in OCD patients and changes after clinical improvement due solely to behavior therapy. The participants were 11 outpatients with OCD and 19 normal controls. The patients received 12 weeks of behavior therapy. We investigated the differences in the behavioral performance and functional magnetic resonance imaging results during the Stroop test in the patients and normal controls, and their changes after treatment in the patients. The patients showed less activation in the anterior cingulate gyrus and cerebellum than control subjects. Following significant improvement in OC symptoms, the cerebellum and parietal lobe showed increased activation, and the orbitofrontal cortex, middle frontal gyrus, and temporal regions showed decreased activation during the Stroop task, and performance of the task itself improved. Our findings suggest that dysfunction of the posterior brain regions, especially the cerebellum, is involved in the pathogenesis of OCD, and that normalization in function can occur with improvement of OC symptoms.     

未服药强迫症患者双侧杏仁核静息态功能连接的初步观察

目的探讨静息状态下未服药强迫症患者双侧杏仁核功能连接的模式。方法纳入符合ICD-10中强迫症诊断标准的40例未服药强迫症患者(强迫症组),38名在性别、年龄和受教育程度与之相匹配的健康对照者(对照组)。采用Y-BOCS、HAMD17、HAMA评估强迫思维、强迫行为以及抑郁、焦虑症状。所有被试者进行全脑静息态fMRI,以左右杏仁核为种子点,采用基于体素的全脑功能连接方法分析强迫症患者静息状态下双侧杏仁核的功能连接模式;采用皮尔逊相关分析方法探讨强迫症患者异常功能连接与临床症状之间的关系。结果与对照组相比,强迫症组左侧杏仁核与右背侧前脑岛(0.16±0.13与0.27±0.13,t=-2.75,P<0.05,高斯随机场理论校正)、左侧杏仁核与左腹侧前扣带回(0.09±0.12与0.19±0.13,t=-3.40,P<0.05,高斯随机场理论校正)功能连接降低;强迫症组左侧杏仁核与右背侧前脑岛之间功能连接Z值与HAMA总分呈正相关(r=0.377,P=0.016,未校正)。结论静息状态下未服药强迫症患者情绪调节网络功能连接降低;左侧杏仁核与右背侧前脑岛之间降低的功能连接可能与强迫症患者的焦虑症状相关。     

西酞普兰与氯米帕明治疗强迫症Meta分析

目的:探讨西酞普兰与氯米帕明治疗强迫症的疗效及不良反应的差异. 方法:用Meta分析对9项西酞普兰与氯米帕明治疗强迫症对照研究进行再分析. 结果:西酞普兰治疗前后的自身对照表明治疗强迫症疗效显著(χ2=135.02,P<0.01).西酞普兰与氯米帕明在治疗2周和治疗结束时的组间疗效比较,分别为d=-0.83,95%CI(-1.34,-0.31),χ2=9.99,P<0.01;YX<合并>=-0.08,95%C/(-0.27,0.10),综合显著性检验差异无显著性(χ2=0.81,P>0.05).提示西酞普兰起效较快,两组疗效相仿.西酞普兰的不良反应显著少于氯米帕明. 结论:西酞普兰治疗强迫症疗效与氯米帕明相仿,但起效快,不良反应少.     

未经治疗的强迫症患者脑白质体积变化的初步研究

目的 探讨未经治疗的强迫症患者大脑白质的体积变化.方法 收集强迫症患者23例和年龄、性别与之相匹配的正常对照23名.采用GE Signa TwinSpeed 1.5T 超导型磁共振成像系统获取3D脑结构图像,然后使用基于体素的形态学分析法(VBM)分析影像数据.采用t检验比较两组间脑白质体积的差异,P＜0.005和体素>200的差异区域行小体积校正(small volume correction,SVC)后仍P＜0.05则差异有统计学意义.结果 患者组下列脑区的白质体积较正常对照组增加:右侧中央前回(t=3.58)、右侧中央后回(t=3.60)、左侧楔前叶(t=3.99)、左侧楔前叶(t=3.24)、右侧楔前叶(t=3.55)和左侧枕中回(t=3.55),差异均有统计学意义(小体积校正后P值均小于0.05);而下列脑区的白质体积减少:右侧额上回(t=3.66)、左侧额上回(t=3.31)、左侧中央后回(t=3.44)、左侧海马旁回/胼胝体(t=3.37)和右侧顶下小叶(t=3.18),差异均有统计学意义(小体积校正后P值均小于0.05).结论 未经治疗的强迫症患者存在多个脑区局部白质体积的增加或降低.     

A cytokine study of adult patients with obsessive-compulsive disorder

ObjectivesWe aimed to determine the plasma levels of cytokines in patients with obsessive-compulsive disorder (OCD) as compared with healthy controls and to investigate whether there is any association between their concentrations and OCD clinical and therapeutic features.MethodsForty patients with OCD and 40 healthy controls had their plasmas assessed for a range of cytokines (tumor necrosis factor-α, or TNF-α), chemokines (CCL2, CCL3, CCL11, CCL24, CXCL8, CXCL9, CXCL10), and other mediators (TNF soluble receptors sTNFR1 and sTNFR2 and interleukin-1 receptor antagonist) by enzyme-linked immunosorbent assay. Patients with OCD were further examined with the Mini-International Neuropsychiatric Interview, the Obsessive-Compulsive Inventory–Revised, and the Beck Depression Inventory.ResultsCompared with healthy controls, patients with OCD exhibited significantly increased plasma levels of CCL3, CXCL8, sTNFR1, and sTNFR2. Among patients with OCD, there was a positive correlation between relative antidepressant dose and sTNFr2 levels. Furthermore, although the levels of sTNFR1 correlated positively with the severity of washing symptoms, CCL24 levels correlated negatively with the severity of hoarding.ConclusionsThe levels of certain immune markers are increased in adult patients with OCD and seem to vary according to predominant symptoms dimensions. Other studies are required to establish whether our findings truly reflect immunologic dysfunction in OCD or are the result of other hidden confounding factors.     

Response acceleration with mirtazapine augmentation of citalopram in obsessive-compulsive disorder patients without comorbid depression: a pilot study

BACKGROUND: Therapeutic action of selective serotonin reuptake inhibitors (SSRIs) is delayed from 8 to 12 weeks in patients with obsessive-compulsive disorder (OCD). Several different agents have been tested to reduce the SSRI therapeutic latency time. Mirtazapine, an antagonist at alpha2-adrenoceptors, does not enhance serotonin (5-HT) neurotransmission directly but disinhibits the norepinephrine activation of 5-HT neurons and thereby increases 5-HT neurotransmission by a mechanism that may not require a time-dependent desensitization of receptors. The present study was undertaken to determine whether the mirtazapine-citalopram combination could induce an earlier and/or greater effect on the 5-HT system in OCD subjects than citalopram alone. METHOD: Forty-nine patients with OCD (DSM-IV) without comorbid depression were randomly assigned to a 2-tailed, single-blind, 12-week clinical trial with citalopram (20-80 mg/day) plus placebo or citalopram plus mirtazapine (15-30 mg/day). Assessments were performed weekly with the Yale-Brown Obsessive Compulsive Scale (YBOCS), the Hamilton Rating Scale for Depression, and the Clinical Global Impressions scale. Data were collected from November 2001 to July 2003. RESULTS: The citalopram plus mirtazapine group achieved a reduction of at least 35% in YBOCS score and a "much improved" or "very much improved" rating on the Clinical Global Impressions-Improvement scale from the fourth week, while the citalopram plus placebo group obtained these results only from the eighth week. The number of responders was higher in the citalopram plus mirtazapine group at the fourth week of treatment, while no difference between groups in the response rate was noted at the eighth and twelfth weeks of treatment. CONCLUSIONS: We found an earlier onset of response action in OCD symptoms and reduced undesired side effects when mirtazapine was added to citalopram. This augmentation strategy deserves clinical and research consideration through further double-blind, placebo-controlled studies.     

有无遗传史的强迫症患者前额叶磁共振质子波谱对照研究

目的 探讨有无遗传史强迫症患者前额叶神经代谢物的变化.方法 采用磁共振质子波谱技术对有遗传史强迫症组(10例)、无遗传史强迫症组(14例)和对照组(12例)的内侧前额叶皮质N-乙酰天冬氨酸(NAA)、肌酸(Cr)和胆碱复合物(Cho)的代谢物含量进行对照研究.结果 有遗传史强迫症组的NAA值(46±8)和NAA/Cr值(1.59±0.24)分别高于对照组的NAA值(37±7)(方差分析LSD法校正,P=0.024)和NAA/Cr值(1.31±0. 21)(方差分析LSD法校正,P=0.006);有遗传史强迫症组的NAA值也高于无遗传史强迫症组的NAA值(37±10)(方差分析LSD法校正,P=0.021);无遗传史强迫症组与对照组相比,NAA/Cr值可见增加趋势(方差分析LSD法校正,P=0.066).结论 有遗传史强迫症患者的神经代谢物NAA与对照组和无遗传史强迫症患者相比在内侧前额叶皮质明显升高.     

西酞普兰合并氯丙咪嗪治疗难治性强迫症

目的探讨西酞普兰以及西酞普兰合并氯丙咪嗪治疗难治性强迫症的疗效和不良反应。方法将16例难治性强迫症患者随机分为2组(n=8)，分别给予西酞普兰，西酞普兰合并氯丙咪嗪治疗。采用耶鲁布朗强迫症量表(YBOCS)和副反应量表(TESS)评定疗效和副反应。结果西酞普兰合并氯丙咪嗪组的所有病人的YBOCS减分率均大于35％，有6例出现副反应。西酞普兰组仅有一例患者的YBOCS减分率大于35％，有3例出现副反应。结论西酞普兰合并氯丙咪嗪治疗难治性强迫症的疗效优于单用西酞普兰，但副反应明显多于西酞普兰组。     

Increased error-related brain activity in pediatric obsessive-compulsive disorder before and after treatment

OBJECTIVE: The error-related negativity is a negative deflection in the event-related potential maximal approximately 50 msec after the commission of errors. The error-related negativity is generated in the anterior cingulate cortex, and both anterior cingulate cortex hyperactivity and increased error-related brain activity have been reported in adults with obsessive-compulsive disorder (OCD). However, no study to date, to the authors' knowledge, has examined error-related brain activity in pediatric patients with OCD, and no study has examined error-related brain activity in OCD both before and after treatment. METHOD: The error-related negativity was measured in 18 treatment-seeking pediatric patients with OCD and 18 age-matched comparison subjects. Of these patients, 10 returned for a second testing session after cognitive behavior therapy; 13 comparison children participated a second time after a comparable interval. RESULTS: In the pretreatment group, the error-related negativity was reliably larger in pediatric patients with OCD in relation to comparison subjects. This difference was also evident after treatment. There was no relationship between error-related negativity and symptom severity or changes in symptom severity. CONCLUSIONS: Consistent with studies in adult patients, increased error-related brain activity is evident in pediatric patients with OCD. Furthermore, increased error-related brain activity does not appear to change as a function of symptom reduction after therapy. These results suggest that an increased error-related negativity may be a trait-like marker for psychopathology and might be a useful endophenotype.     

强迫症、抑郁症及焦虑症患者血小板5-羟色胺浓度的对照研究

目的　研究 5 羟色胺 ( 5 HT)在强迫症发病中的作用及强迫思维与强迫动作亚组、抑郁症及焦虑症患者间血小板 5 HT含量的差异。方法　采用高效液相色谱法 ,分别测定 2 9例强迫症患者 [(强迫症组 ,根据Y BOCS强迫量表因子得分将其分为强迫思维 ( 16例 )、强迫动作 ( 7例 )和混合性( 6例 ) 3组 ]、2 0例抑郁障碍患者 (抑郁症组 )、17例焦虑障碍患者 (焦虑症组 )和 2 8名正常人 (正常人组 )的血小板 5 HT含量。结果　强迫症组血小板 5 HT水平 [( 139± 172 ) μg/L]低于正常人组 [( 2 4 8±2 15 ) μg/L]及焦虑症组 [( 397± 4 0 1) μg/L],差异具有显著性 (P =0 0 39;P =0 0 2 0 ) ;与抑郁症组 [( 2 0 2± 16 2 ) μg/L]的差异无显著性 ( P >0 0 5 ) ;强迫思维 [( 85± 6 6 ) μg/L]与强迫动作组 [( 16 9± 10 0 ) μg/L]间血小板 5 HT含量的差异有显著性 (P =0 0 2 5 )。结论　强迫症患者 5 HT浓度变化与抑郁障碍患者趋同 ,与焦虑障碍患者的差异有显著性 ;单纯强迫思维者的 5 HT浓度与单纯强迫动作患者的差异有显著性     

首诊强迫症患者的认知功能特点研究

目的探讨首诊强迫症患者的认知功能特点。方法选取我院符合ICD-10的首诊强迫症住院患者24人为病例组;从医护人员中选取年龄、性别及受教育程度类似的被试24人作为对照组。分别对两组人员进行划销测验和《临床记忆量表》检查,应用SPSS13.0进行统计分析。结果在划销测验中,强迫症组与对照组相比反应时延长,正确数减少,漏划数增加,且差异显著（P〈0．05）;在《临床记忆量表》测验中两组的记忆商、联想学习、图像自由回忆、人像特点回忆得分均有显著差异（P〈0．05）,强迫症组较差,指向学习、无意义图形再认得分两组差异不显著（P〈0．05）。结论强迫症患者存在明显的认知功能障碍,认知功能损害是使其症状不易缓解的原因之一。     

全病程病案管理模式对首诊强迫症患者24周疗效随访研究

目的比较全病程病案管理模式和门诊治疗模式干预首诊强迫症急性期和巩固期的疗效。方法前瞻性平行对照研究。在符合ICD-10强迫症诊断标准的100例患者中,随机分配48例接受全病程病案管理,另52例仅接受门诊治疗,对所有病例跟踪随访24周。在治疗前基线、第2周、第4周、第8周、第24周随访评定病情严重程度。结果（1）全病程管理组48例随访24周没有病例脱落;对照组52例,随访24周脱落14例（26．92％）。（2）全病程管理组治疗第8周和第24周的Yale-Brown强迫症量表（Y-Brown）总分和汉密顿抑郁量表（HAMD17）、汉密顿焦虑量表（HAMA）总分的均值显著低于对照组（P〈0．05）。（3）全病程管理组第8周和第24周疗效显著高于对照组（P〈0．01）。全病程管理组第24周的显效率显著高于对照组（P〈0．01）。（4）急性期随访全病程管理组治疗终止治疗率显著低于对照组（P〈0．05）。结论全病程管理模式干预首诊强迫症急性期和巩固期的疗效和依从性优于单纯门诊治疗模式。     

强迫症患者的Quisi睡眠监测研究

目的 探讨强迫症患者Quisi睡眠参数的变化特征.方法 应用德国Quisi仪对27例强迫症(OCD)患者的Quisi进行全夜监测,并与33名正常受试者(NC)对照.结果 与正常成人组比较,OCD组Quisi主要表现为REM睡眠潜伏期前移,REM活动度,REM强度,REM密度和第1阶段睡眠均增加以及睡眠潜伏期延迟和睡眠效率降低.结论 在缺乏相关设备的基层医院,Quisi技术可用于对强迫症的检测.     

强迫症患者局部脑血流灌注研究

目的　探讨强迫症(OCD)患者局部脑血流灌注(rCBF)特点及临床症状与rCBF的关系。方法　对2 8例符合国际疾病分类第1 0版(ICD 1 0 )强迫障碍诊断标准患者和1 5名正常人进行单光子发射计算机断层扫描(SPECT)脑显像分析。用耶鲁 布朗强迫评定量表(YBOCS)、Hamilton焦虑量表(HAMA)和Hamilton抑郁量表(HAMD)对患者临床症状进行评定。结果　OCD患者两侧丘脑、顶叶和基底神经节的平均放射性计数百分数(PMRC)显著高于正常组;右颞PMRC明显低于正常组;且正常组两侧颞叶和顶叶PMRC值差异非常显著。在强迫恐惧/洗涤、回避组,YBOCS强迫行为分量表评分与右基底PMRC显著正相关(r =0 .70 1 )。结论　OCD患者两侧丘脑、顶叶和基底神经节的血流灌注增加和功能亢进;右颞血流灌注减少和功能低下,两侧颞叶和顶叶血流灌注的不对称性与正常人显著不同,后者的不对称性非常显著;在强迫恐惧/洗涤、回避组,强迫行为与右基底节功能增强有关。