首发抑郁症患者局部脑葡萄糖代谢的PET初步研究

目的　探讨首发抑郁症脑葡萄糖代谢特点及与临床症状、神经心理的相关性。方法　对14例首发抑郁症患者与 11例健康对照者进行正电子发射断层扫描 (positionemissiontomography ,PET)。抑郁症患者行汉密尔顿抑郁量表 (HAMD17)、Montgomery Asberg抑郁量表 (MADS)、汉密尔顿焦虑量表 (HAMA)、临床疗效总评量表 (CGI)、中国修订版韦克斯勒成人智力量表 (WAIS RC)、中国修订版韦克斯勒记忆量表 (WMS RC)、威斯康星卡片分类测验 (WCST)评定。结果　 (1)感兴趣区 (ROI)分析显示抑郁症组右侧额上回、右侧扣带回的rCMRglc显著低于健康对照组 (P <0 0 5 ) ;抑郁症组右侧额上回rCMRglc降低甚于左侧额上回rCMRglc降低 (P <0 0 5 )。 (2 )抑郁症组左侧、右侧rCMRglc与其MADS评分值呈负相关 (分别为P <0 0 5、P <0 0 1) ;右侧额上回、双侧额中回、双侧扣带回、双侧颞叶rCMRglc与SI评分值呈负相关 (除右颞叶P <0 0 1,余区域P <0 0 5 ) ;左侧额下回rCMRglc与其WMS评分值呈正相关P <0 0 5 )。 (3)抑郁症组右侧丘脑rCMRglc与其 1→ 10 0数数值呈正相关 (P <0 0 5 ) ;右侧额中回rCMRglc与其图片值呈负相关 (P <0 0 5 ) ;右侧岛叶rCMRglc与其再认值呈正相关 (P <0 0 5 ) ;左侧颞叶、左侧枕叶rCMRglc与其理解记忆     

抑郁症患者局部脑葡萄糖代谢的SPM分析

目的探讨首发抑郁症患者的局部脑葡萄糖代谢特点。方法对14例首发并且符合DSM-Ⅳ的抑郁症患者进行汉密尔顿抑郁量表(HAMD17)、Montgomery-Asberg抑郁量表(MADS)、汉密尔顿焦虑量表(HAMA)的评估及18F-FDGPET检查;对11例年龄、性别、文化程度均相匹配的健康对照者进行18F-FDGPET检查。18F-FDGPET显像后,用统计参数地图(SPM,P值设为0.001)方法分析抑郁症组和健康对照组的局部脑葡萄糖代谢分布差别。结果SPM分析显示双侧额上回、右侧额中回、右侧额叶内侧,右侧脑岛葡萄糖代谢率显著低于对照组(P<0.001);左侧丘脑,左侧前扣带回,双侧小脑前叶山顶、右侧小脑后叶山坡,左侧枕中回,左侧颞中、下回葡萄糖代谢率显著高于对照组(P<0.001)。结论首发抑郁症患者存在皮质-丘脑-边缘回路代谢异常;小脑的代谢异常是一个值得关注的区域;从神经影像学角度为抑郁症的早期诊断提供参考依据。     

抑郁症患者局部脑血流的研究

目的：了解抑郁症患者局部脑血流灌注的特点：方法：应用单光子发射计算机断层扫描对20例抑郁症患者及18例正常对照者局部脑血流灌注进行对比分析。结果：抑郁症组双侧基底核、双侧额叶、左颞叶及左枕叶局部血流低灌注；抑郁症组与对照组左右大脑半球局部血流灌注无显著性差异：结论：抑郁症患者局部脑血流存在低灌注，但未发现局部脑血流低灌注有侧化现象。     

盐酸氟西汀治疗首发抑郁症患者脑局部葡萄糖代谢变化的PET研究

目的探讨首发抑郁症患者经盐酸氟西汀治疗后脑葡萄糖代谢率的变化。方法8例首发抑郁症患者经盐酸氟西汀 治疗前、后进行正电子发射断层扫描术(positron emission tomographyr,PET),并采用统计参数地图(SPM,P值设为0．001)方法分析。 以汉密顿抑郁量表(HAMD)、Montgomery-Asberg抑郁量表(MADS)、汉密顿焦虑量表(HAMA)、临床疗效总评量表(CGI)、中国修订韦 克斯勒成人智力量表(WAIS-RC)、中国修订韦克斯勒记忆量表(WMS—RC)、威斯康星卡片分类测验(WCST)评价临床症状改善及神 经心理变化。结果SPM分析显示,首发抑郁症经盐酸氟西洒治疗有效者的左侧额上回、左侧额中回、右侧脑岛、左侧顶上小叶、右侧 顶下小叶及右侧小脑后叶的局部葡萄糖代谢率显著高于治疗前(P<0．001);左侧丘脑、左侧豆状核的局部葡萄糖代谢率显著低于治 疗前(P<0．001)。结论盐酸氟西汀可使首发抑郁症患者的前额叶皮质、丘脑的局部葡萄糖代谢率发生变化。     

不同严重程度帕金森病患者脑葡萄糖代谢变化特点的临床研究

目的:探讨早、晚期帕金森病（PD）患者不同脑区葡萄糖代谢变化的特点,寻求PD严重度的新型生物学标志物。方法:19例早期PD（H-YⅠ～Ⅱ级）组、14例中晚期PD（H-YⅢ～V级）组患者及50名年龄匹配的健康对照组接受静脉注射¹⁸F-FDG PET脑断层显像,应用参数图分析法进行数据分析,比较各组间受试者脑内葡萄糖代谢变化的差异和特点。结果:与健康对照组比较,早期PD患者的丘脑、豆状核、小脑葡萄糖代谢增高;中晚期双侧丘脑、豆状核、小脑代谢增高,双侧顶叶葡萄糖代谢减低。结论:PD患者存在双侧丘脑、豆状核、小脑葡萄糖代谢增高,双侧顶叶葡萄糖代谢减低的代谢异常模式,且随着病情严重度的不同而变化,应用于PD严重度的客观评价,值得进一步研究。     

抑郁症患者局部脑血流变化的SPECT研究

目的用SPECT测定抑郁症患者的局部脑血流(rCBF),比较乙酰唑胺脑负荷试验后脑血流灌注变化,观察抑郁症患者脑血管的调节能力,以及是否存在潜在缺血灶。方法以18例未经抗抑郁治疗的抑郁症患者为研究对象,19名正常人作为对照组,行单光子发射计算机断层扫描(SPECT)检查。抑郁症患者48h后口服乙酰唑胺2g,再行SPECT检查。观察服用乙酰唑胺前后脑内血流的变化。结果抑郁组患者双侧额叶、颞叶的rCBF显著下降(P<0.01～0.05),左顶叶、右基底节rCBF也明显降低(P<0.05);同时,抑郁症患者局部脑血流低灌注存在不对称性,左侧灌注更低。服用乙酰唑胺后,原脑内各血流灌注下降部位恢复正常血供,未发现潜在缺血病灶。结论抑郁症患者某些特定部位存在脑血流灌注下降;乙酰唑胺脑负荷SPECT试验未发现抑郁症患者存在潜在缺血部位,而且使其局部脑血流低灌注状态恢复正常。     

阿尔茨海默病患者脑葡萄糖高代谢分析

为探讨阿尔茨海默病（ Alzheimer＇s disease, AD）患者脑葡萄糖代谢增高的意义，而对其脑部高代谢进行正电子发射断层成像（ positron emission tomography, PET）观察。     

多系统萎缩不同亚型间的临床特征及脑葡萄糖代谢差异分析

目的分析多系统萎缩-帕金森亚型和多系统萎缩-小脑共济失调亚型患者的临床特征以及18氟-脱氧葡萄糖正电子发射断层(l8F-FDG PET)显像的特征差异。方法收集8例多系统萎缩-帕金森亚型患者和17例多系统萎缩-小脑共济失调亚型患者的临床资料,回顾性分析包括统一帕金森病评定量表-运动部分(UPDRS Ⅲ)评分和Hoehn-Yahr分级的运动症状评估,认知功能、抑郁、嗅觉、快速眼动期睡眠行为紊乱等非运动症状评估,以及基于l8F-FDG PET脑葡萄糖代谢显像的特征差异。结果多系统萎缩-帕金森亚型与多系统萎缩-小脑共济失调亚型患者UPDRS Ⅲ评分(P=0.004)及Hoehn-Yahr分级(P<0.001)比较,差异有统计学意义,而非运动症状组间比较,差异无统计学意义(P>0.05)。多系统萎缩-帕金森亚型在基底节(尤其是后壳核)脑葡萄糖代谢(P<0.001)、小脑及顶枕叶呈低代谢,多系统萎缩-小脑共济失调亚型基底节脑葡萄糖代谢未见减低,仅在小脑和枕叶呈低代谢。结论多系统萎缩的临床特征异质性大,l8F-FDG PET脑葡萄糖代谢显像特征差异可为深入研究多系统萎缩的发病机制、开发更精准治疗奠定基础。     

发作间期^14F—FDG PET在难治性癫痫手术定位中的价值

许多学者认为脑PET显像不仅能诊断癫痫,且能对癫痫灶准确定位,为癫痫的手术、立体定向和放射外科治疗提供了定位依据。本研究分析了12例难治性癫痫患者术前~(18)F-FDG PET脑显像与术中皮层脑电图(ECoG)检查、术后病理结果的关系,以探讨术前~(18)F-FDG PET脑显像对癫痫灶定位的价值。1 资料与方法1.1 临床资料 本组共12例,男8例,女4例,年龄4～48岁,平均21.5岁;病程1.5～20年,平均4.5年;发作类型按照国际癫痫分类标准:全身性发作6例,复杂部分性发作4例,单纯部分性发作1例,部分性发作继发全身性发作1例;均长期服用抗癫痫药物治疗,临床诊断为难治性癫痫,有明确的手术适应症;术前所有患者均行2～5次EEG或动态     

醒脑开窍针刺法对急性基底核脑梗死患者脑葡萄糖代谢的影响：多中心随机对照

目的 探讨针刺“醒脑开窍”组穴对急性脑梗死患者脑葡萄糖代谢的经穴特异性效应,,研究针刺治疗脑梗塞的中枢机制。方法 选取急性基底节脑梗死患者18例,分为经穴组（基础治疗+醒脑开窍主穴针刺）、非经非穴组（基础治疗+非经非穴针刺）和对照组（基础治疗）,每组6例。以脑梗死患者治疗前后PET-CT的18F-FDG（18氟标记脱氧葡萄糖）显像资料作为中枢代谢改善评价标准,从分子水平动态的观察针刺经穴、非经穴及无针刺干预对脑梗死全脑、脑梗死中心和梗死周围水肿带葡萄糖代谢的影响。结果 观察组患者全脑代谢、脑梗死中心和梗死周围水肿带代谢呈明显激活状态,其激活广度及强度均明显优于非经非穴组和对照组。结论 醒脑开窍针刺法治疗基底节梗死病人,可有效改善病人脑内相应部位葡萄糖代谢,与非经非穴相比有显著的特异性效应。     

Regional cerebral glucose metabolic abnormalities in bipolar II depression.

BACKGROUND: Functional neuroimaging studies of bipolar disorder (BD) performed in conjunction with antidepressant treatment trials generally require that patients remain on mood stabilizers to reduce the risk of inducing mania; yet, it is unknown whether the metabolic abnormalities evident in unmedicated BD depressives remain detectable in patients receiving mood stabilizers. This study investigated whether cerebral metabolic abnormalities previously reported in unmedicated BD subjects are evident in depressed bipolar disorder type II (BD II) subjects receiving lithium or divalproex. METHODS: Using [18F]-fluorodeoxyglucose-positron-emission tomography, cerebral glucose metabolism was compared between 13 depressed BD II subjects on therapeutic doses of lithium or divalproex and 18 healthy control subjects. Regional metabolism was compared between groups in predefined regions of interest. RESULTS: Metabolism was increased in the bilateral amygdala, accumbens area, and anteroventral putamen, left orbitofrontal cortex and right pregenual anterior cingulate cortex in depressives versus control subjects. Post hoc exploratory analysis additionally revealed increased metabolism in left parahippocampal, posterior cingulate, and right anterior insular cortices in depressives versus control subjects. Correlational analyses showed multiple limbic-cortical-striatal interactions in the BD sample not evident in the control sample, permitting sensitive and specific classification of subjects by discriminant analysis. CONCLUSIONS: These results confirm previous reports that bipolar depression is associated with abnormally increased metabolism in the amygdala, ventral striatum, orbitofrontal cortex, anterior cingulate, and anterior insula, and extend these results to bipolar disorder type II depressives on lithium or divalproex. They also implicate an extended functional anatomical network known to modulate visceromotor function in the pathophysiology of BD II depression.     

Mirtazapine for treatment-resistant depression: a preliminary report

OBJECTIVE: To describe the effectiveness and tolerability of mirtazapine, a noradrenergic and specific serotonergic antidepressant, in the open-label treatment of patients with depression who were resistant to other antidepressant agents. METHODS: The charts of 24 patients who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (DSM-IV) criteria for major depressive disorder and were treated with mirtazapine after partial or nonresponse to standard antidepressants were reviewed for clinical response. Outcome was determined by using the Clinical Global Impressions of Improvement (CGI-I) Scale. RESULTS: Symptomatic improvement was observed in 9 (38%) of 24 patients during an average of 14.1 months of mirtazapine treatment at a mean dose of 36.7 mg/day. Five (21%) patients discontinued mirtazapine because of side effects such as fatigue, weight gain and nausea. Five (21%) patients were receiving combination therapy with another antidepressant when mirtazapine treatment was initiated. CONCLUSIONS: This open-label study suggests that a subgroup of patients with treatment-resistant depression may benefit from mirtazapine treatment. Further controlled studies are required to demonstrate the efficacy of mirtazapine in treatment-resistant depression.     

Regional cerebral blood flow in weight-restored anorexia nervosa: a preliminary study

Twenty-one individuals (19 females, two males) with teenage-onset anorexia nervosa (AN), 19 of whom were weight restored, were assessed using single-photon emission computed tomography (SPECT) 7 years after onset of AN, at a mean age of 22 years. For comparison we recruited a younger group without neuropsychiatric disorder (mean age 9:8 years; five females, four males) who underwent SPECT at follow-up after an operation for coarctation of the aorta or because of lymphatic leukaemia. Ethical considerations precluded the study of regional cerebral blood flow (rCBF) in participants with completely normal development. The group with AN showed marked hypoperfusion of temporal, parietal, occipital, and orbitofrontal lobes compared to the contrast group. rCBF was not correlated to body mass index in any of the groups. Results suggest that, even long after re-feeding has occurred, AN may be associated with moderate to severe cerebral blood flow hypoperfusion in the temporoparietal (or temporoparietooccipital) region and in the orbitofrontal region. A limitation of the study is that the young contrast group in this study could be expected to have a higher global rCBF than the group with AN. However, this should not significantly affect the relative values used in this study.     

Pramipexole in treatment-resistant depression: a 16-week naturalistic study

Lattanzi L, Dell'Osso L, Cassano P, Pini S, Rucci P, Houck PR, Gemignani A, Battistini G, Bassi A, Abelli M, Cassano GB. Pramipexole in treatment‐resistant depression: a 16‐week naturalistic study. Bipolar Disord 2002: 4: 307–314. © Blackwell Munksgaard 2002 Objective: To assess the antidepressant efficacy and tolerability of adjunctive pramipexole, a D₂–D₃ dopamine agonist, in patients with drug‐resistant depression. Methods: The study sample consisted of in‐patients with major depressive episode, according to the DSM‐IV, and drug resistance. Pramipexole was added to antidepressant treatment with TCA or SSRI, at increasing doses from 0.375 to 1.0 mg/day. Two independent response criteria were adopted: a >50% reduction of the Montgomery–Asberg Depressive Rating Scale (MADRS) total score and a score of 1 or 2 on the Clinical Global Impression scale (CGI‐I) at endpoint. Side‐effects were assessed by the Dosage Record Treatment Emergent Symptom Scale (DOTES). Results: Thirty‐seven patients were enrolled. Of these, 16 had unipolar depression and 21 had bipolar depression. Six patients dropped out in the first week. Of the 31 patients included in the analyses, 19 completed the 16‐week follow‐up. Mean maximal dose of pramipexole was 0.95 mg/day. Mean scores on MADRS decreased from 33.3 ± 8.4 at baseline to 13.9 ± 11.5 at endpoint (p < 0.001) and the CGI‐S decreased from 4.6 ± 0.8 at baseline to 2.8 ± 1.3 at endpoint (p < 0.001). At endpoint, 67.7% (21/31) of patients were responders on MADRS and 74.2% on CGI‐I. Of the 37 patients enrolled, 10 discontinued pramipexole because of adverse events. Conclusions: These preliminary data suggest that pramipexole adjunction to antidepressant treatment may be effective and well tolerated in patients with resistant major depression.     

Regional cerebral blood flow abnormalities in late-life depression:Relation to refractoriness and chronification

Abstract We examined patterns of regional cerebral blood flow (rCBF) abnormalities in 18 patients with major depressive disorder in late life using single photon emission computed tomography (SPECT) and (^99mTc-hexamethyl-propylenamine oxime (^99mTc-HMPAO). Compared with 13 age-matched controls, relative rCBF was significantly decreased bilaterally in the anterior cingulate gyrus, the prefrontal cortex, the temporal cortex, the parietal cortex, the hippocampus and the caudate nucleus. However, it was not correlated with the severity of depression or global cognitive dysfunction. In 10 patients with a prolonged depressive episode or prolonged residual symptoms (the refractory subgroup), robust and extensive decreases in rCBF were found compared with controls and the rCBF decreased significantly in the anterior cingulate gyrus and the prefrontal cortex compared with that in the non-refractory subgroup. In the non-refractory subgroup, rCBF decreased significandy in the caudate nucleus and tended to decrease in the anterior cingulate gyrus compared with controls. These findings indicate that dysfunction of the limbic system, the cerebral association cortex and the caudate nucleus may be implicated in late-life depression and that robust and extensive hypoperfusion, especially in the anterior cingulate and the prefrontal regions, may relate to refractoriness or chronification of depression.     

Regional cerebral cortical deficits in the immune-deficient nude mouse: a preliminary study

This report examines the morphology of the cerebral cortex in the nude mouse (nu/nu) compared with the BALB/c(+/+). Our experiments indicated that the thickness of the lateral frontal lobe was significantly reduced (8%; P less than 0.005) in the 4-month-old, female nude mouse compared with a BALB/c mouse of like sex and age. In addition, the left hemisphere was, in general, thinner in the nude than in the BALB/c, with area 18 being significantly thinner (2%; P less than 0.005). Oligodendrocytes were less in area 18 in the nude by 25% (P less than 0.02) in contrast to the BALB/c. In some respects these results extend the work of others. In previously published experiments, we showed that the thickness of the frontal cortex from enriched and impoverished female rats (from 60 to 116 days of age) differed by 2 to 3% (P less than 0.001) and in male rats by 3 to 4% (P less than 0.001). The oligodendrocytes in area 18 in the male differed by 20% (P less than 0.02) in rats exposed to their respective enriched or impoverished environments from 25 to 105 days of age. Thus, we have shown that the frontal cortical morphology as well as the occipital cortical oligodendrocytes were altered in both immune-deficient animals and environmentally stimulated or impoverished animals. Based on these separate sets of data, we will be interested to learn if our environmental conditions can alter the immune system and if so by what mechanism.     

Regional cerebral metabolic rate for glucose during hyperbaric oxygen-induced convulsions

Hyperbaric oxygen-induced convulsions in awake unrestrained rats are preceded by electrocorticographic changes including paroxysmal electrical discharges (PED). During oxygen induced convulsions, alterations in regional cerebral metabolic rate for glucose (rCMRgl) were autoradiographically measured and compared with rCMRgl results obtained during pre-convulsive periods in an earlier study. Statistically elevated rCMRgl during oxygen-induced convulsions were found in globus pallidus, substantia nigra, limbic structures, and cerebellar cortex. Significant reductions were found largely in auditory structures and cerebral cortex. This pattern of changes in rCMRgl resembles the pattern of changes during successive PED in the absence of overt convulsions. This similarity may indicate that a common sequence of biochemical changes leads to both oxygen-induced pre-convulsive as well as convulsive electrical discharges.     

Disrupted regional homogeneity in treatment-resistant depression: a resting-state fMRI study

Background

Using a newly developed regional homogeneity (ReHo) approach, we were to explore the features of brain activity in patients with treatment-resistant depression (TRD) in resting state, and further to examine the relationship between abnormal brain activity in TRD patients and specific symptom factors derived from ratings on the Hamilton Rating Scale for Depression (HRSD).

Methods

24 patients with TRD and 19 gender-, age-, and education-matched healthy subjects participated in the fMRI scans.

Results

1.

Compared with healthy controls, decreased ReHo were found in TRD patients in the left insula, superior temporal gyrus, inferior frontal gyrus, lingual gyrus and cerebellum anterior lobe (culmen) (p < 0.05, corrected).

2.

Compared with healthy controls, increased ReHo were found in the left superior temporal gyrus, cerebellum posterior lobe (tuber), cerebellum anterior lobe (culmen), the right cerebellar tonsil and bilateral fusiform gyrus (p < 0.05, corrected).

3.

There was no correlation between the ReHo values in any brain region detected in our study and the patients' age, years of education, illness duration, HRSD total score and its symptom factors.

Limitation

The influence of antidepressants to the brain activity in TRD patients was not fully eliminated.

Conclusions

The pathogenesis of TRD may be attributed to abnormal neural activity in multiple brain regions.     

Ropinirole in treatment-resistant depression: a 16-week pilot study.

OBJECTIVE: The study aimed to assess the antidepressant efficacy and tolerability of adjunctive ropinirole in outpatients with treatment-resistant depression (TRD). METHOD: The study sample consisted of patients with a major depressive episode (diagnosed according to DSM-IV criteria) and TRD. Ropinirole 0.25 to 1.5 mg daily was added to tricyclic antidepressants or selective serotonin reuptake inhibitors. We conducted assessments at baseline and at weeks 2, 4, 8, 12, and 16. We defined response as a 50% or greater reduction of the Montgomery-Asberg Depression Rating Scale (MADRS) total score plus a score of 1 ("very much improved") or 2 ("much improved") on the Clinical Global Impression of Improvement scale at endpoint. Tolerability was monitored with the Dosage Record Treatment Emergent Symptom Scale. RESULTS: Seven patients had major depressive disorder, and 3 had bipolar II disorder. The mean maximum dose of ropinirole was 1.33 mg daily. Mean (SD) scores on the MADRS decreased from 29.6 (7.6) at baseline to 16.9 (12.1) at endpoint (P < 0.02). At endpoint, 4 of 10 (40%) patients were responders. Two patients discontinued ropinirole because of dizziness. CONCLUSIONS: These pilot data suggest that, in selected cases of TRD, ropinirole augmentation of antidepressants is effective and relatively well tolerated.     

Regional cerebral glucose metabolism and anxiety symptoms in bipolar depression: Effects of levothyroxine

We examined the relationships between regional brain activity and anxiety in bipolar depressed patients receiving adjunctive treatment with levothyroxine. Regional brain activity was assessed with positron emission tomography and [¹⁸F]fluorodeoxyglucose in 10 euthyroid, depressed bipolar women before and after 7 weeks of adjunctive therapy with levothyroxine. The primary biological measures were relative (to global) regional radioactivity as a surrogate index of glucose metabolism in pre-selected brain regions. Relationships were assessed between regional brain activity and anxiety symptoms while controlling for depression severity. At baseline, Trait Anxiety Inventory measures covaried positively with relative brain activity bilaterally in the dorsal anterior cingulate, superior temporal gyri, parahippocampal gyri, amygdala, hippocampus, ventral striatum, and right insula; state anxiety showed a similar pattern. After treatment anxiety was improved significantly. Change in trait anxiety covaried positively with changes in relative activity in right amygdala and hippocampus. Change in state anxiety covaried positively with changes in relative activity in the hippocampus bilaterally and left thalamus, and negatively with changes in left middle frontal gyrus and right dorsal anterior cingulate. Results indicate that comorbid anxiety symptoms have specific regional cerebral metabolic correlates in bipolar depression and cannot only be explained exclusively by the depressive state of the patients.