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抑郁症的基础与认知激活脑血流灌注异常类型
http://www.100md.com 《中华核医学杂志》 2000年第4期
     作者:赵晋华 林祥通 江开达 昂秋青 施慎逊 薛方平

    单位:赵晋华(第一作者现在首都医科大学附属北京同仁医院,100730);林祥通 江开达 昂秋青 施慎逊 薛方平(上海医科大学附属华山医院 200040)

    关键词:抑郁症;脑;体层摄影术,发射型计算机,单光子;威斯康星

    中华核医学杂志000408 【摘要】 目的 观察抑郁症患者基础和认知激活脑血流灌注显像异常类型,以了解不同发病年龄对抑郁症脑血流灌注的影响。方法 研究对象分4组:非老年期抑郁症组、非老年期对照组、老年期抑郁症组和老年期对照组。非老年期和老年期抑郁症组均为初发抑郁,未经抗抑郁治疗,经精神疾病CCMD-2-R、ICD-10分类,诊断为中度抑郁发作伴躯体症状,Hamilton抑郁量表评分(24项)为24~49分。抑郁症组和对照组均无脑血管病危险因素,均为右利手。老年期抑郁症组及老年期对照组CT检查结果均正常。39例非老年期患者中25例行双日法基础与Wisconsin卡片分类试验(WCST)认知激活脑SPECT显像,另14例仅行基础脑SPECT显像。17例非老年期对照者均行双日法基础与WCST认知激活脑SPECT显像。18例老年期抑郁症患者中12例行双日法基础与WCST认知激活脑SPECT显像,另6例仅行基础脑SPECT显像。21例老年期正常对照者中18例行双日法基础与WCST认知激活脑SPECT显像,另3例仅行基础脑SPECT显像。结果 ①非老年期抑郁症患者的基础局部脑血流(rCBF)灌注显像示额叶、颞叶低灌注;激活显像时,额叶和颞叶的低灌注更加明显,并且顶叶也有明显的血流灌注减低。与对照组相比,差异有显著性。②老年期抑郁症患者的基础rCBF脑显像示额叶、颞叶和右基底节低灌注;激活显像时,额叶、颞叶的低灌注更加明显,并且右顶叶和左基底节也有明显的血流灌注减低。与对照组相比,差异有显著性。结论 ①非老年期和老年期抑郁症都存在额叶、颞叶局部血流低灌注,这与抑郁症患者的心境低落、思维阻滞、注意力不集中和记忆力减退密切相关。非老年期和老年期抑郁症都是涉及额叶、颞叶和其他大脑皮层及皮层下结构病理过程的临床综合征。②与非老年期抑郁症的血流灌注异常类型比较,老年期抑郁症具有基底节血流灌注减低。③WCST认知激活脑血流灌注显像可提高对抑郁症的诊断信度,对抑郁症的病因学研究及其诊断、鉴别诊断有一定作用。
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    Hypoperfusion in baseline and cognitively activated brain SPECT imaging of adult and elderly patients with depression

    ZHAO Jinhua LIN Xiangtong JIANG Kaida et al

    (Hua Shan Hospital, Shanghai Medical University, Shanghai 200040, China)

    【Abstract】 Objective To evaluate the rCBF abnormalities of the baseline and cognitively activated rCBF imaging in unmedicated adult and elderly patients with depression. Methods The subjects were divided into four groups: depressed adults, normal adult controls, depressed elders and normal elderly controls. All depressed patients were unmedicated and the diagnoses (depression of moderate degree with accompanying somatization) were confirmed by the ICD-10 criteria. Age range of the 39 depressed adult patients was 17~55 years. 17 age-matched normal adult controls (age range 21~50 years) were studied under identical conditions. The age range of 18 depressed elderly patients was 62~76 years. 21 age-matched normal elderly controls (age range 60~72 years) were studied under identical conditions. Baseline and cognitively activated 99 Tcm-ECD SPECT were performed on 25 of the 39 adult patients with depression and 17 normal adult controls. Baseline 99 Tcm-ECD SPECT only was performed on the remaining 14 patients with depression. Baseline and cognitively activated 99 Tcm-ECD SPECT were performed on 12 of the 18 elderly patients with depression and 18 of the 21 normal elderly controls. Baseline 99 Tcm-ECD SPECT only was performed on the remaining elderly patients and 3 normal elderly controls. Results ①The characteristic abnormalities of baseline and cognitively activated brain SPECT imaging of depression in adults: the baseline rCBF values of frontal and temporal lobe decreased significantly and the activated rCBF values of frontal, temporal lobe decreased more evidently than that in the baseline imaging and additionally decreased activated rCBF values in parietal lobe were found. ②The characteristic abnormalities of baseline and cognitively activated brain SPECT imaging of elderly patients with depression: the baseline rCBF values of frontal, temporal lobe and right basal ganglia decreased significantly and the activated rCBF values of frontal , temporal, right parietal lobe and left basal ganglia aslo decreased. Conclusions ①Hypoperfusion of frontal and temporal cortex was identified in adult and elderly patients with depression. ②The hypoperfusion of frontal and temporal cortex may be the cause of cognitive disorder and the depressed mood in patients with depression. ③Compared with the depressed adult patients, there is additional hypoperfusion of basal ganglia in the depressed elderly patients. ④Cognitively activated brain perfusion imaging is useful to diagnose depression more accurately.
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    【Key words】 Depression; Brain; Tomography, emission-computed, single-photon; Wisconsin

    抑郁症是一种以心境低落为主要特点的综合征。近年应用SPECT和PET脑显像探讨抑郁症的病理基础和脑功能状态,取得了一些进展[1-3]。本研究选择中度抑郁发作伴躯体症状、未经过抗抑郁治疗的初发患者作为研究对象,进行基础和认知激活脑血流灌注显像,观察非老年期和老年期抑郁症患者脑血流灌注的情况,现报道如下。

    资料和方法

    1. 研究对象。研究对象分4组:非老年期抑郁症组,非老年期对照组,老年期抑郁症组和老年期对照组(表1)。抑郁症患者均为本院疑难杂症心理咨询门诊及上海市精神卫生中心门诊及住院病人,均为初发抑郁,病程为3个月~2 a,大部分为0.5 a左右,未经抗抑郁治疗,经精神疾病CCMD-2-R、ICD-10分类,诊断为中度抑郁发作伴躯体症状,Hamilton抑郁量表评分(24项)为24~49分。所有研究对象均无脑血管病危险因素,均为右利手。老年期抑郁症组及其对照组CT结果均正常。非老年期抑郁症患者与非老年期对照组年龄间差异无显著性。老年期抑郁症患者痴呆简易筛查量表评分均高于22分,与老年期对照组年龄间差异无显著性。
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    2. 99 Tcm-双半胱乙酯(ECD)SPECT基础与认知激活脑血流灌注显像(表1)。基础与认知激活SPECT显像步骤及半定量分析方法参见文献[3]。基础显像为普通脑血流灌注显像。认知激活显像:采用Wisconsin卡片分类试验(WCST)进行认知激活,半定量分析在横断面图像7,8,9,10,11帧上进行,将各感兴趣区(ROI)的平均计数与同侧小脑的最高计数相除,得到各ROI的局部脑血流(rCBF)比值。

    3. 统计学处理。数据以±s表示,并行t检验。

    表1 各组研究对象的临床资料及显像情况 组 别

    例数

    性别
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    年龄

    (岁)

    脑灌注显像

    男

    女

    基础+认知激活

    单纯基础

    非老年期抑郁症组

    39

    16

    23

    17~55

    25
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    14

    非老年期对照组

    17

    9

    8

    21~50

    17

    0

    老年期抑郁症组

    18

    12

    6

    62~76
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    12

    6

    老年期对照组

    21

    11

    10

    60~72

    18

    3

    合 计

    95

    48

    47

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    23

    结 果

    1. 非老年期抑郁症的基础与认知激活脑灌注显像特点。39例非老年期抑郁症患者和17例年龄、文化程度匹配的非老年期对照者各大脑皮层及皮层下结构的基础和激活rCBF比值见表2。非老年期抑郁症患者的基础脑灌注显像示额叶、颞叶低灌注;激活显像时,额叶和颞叶的低灌注更加明显(图1),并且顶叶也有明显的血流灌注减低。与对照组相比,差异有显著性。

    2. 老年期抑郁症的基础与认知激活脑灌注显像特点。18例老年期抑郁症患者和21例年龄、文化程度匹配的老年期对照者各大脑皮层及皮层下结构的基础和激活rCBF比值见表3。老年期抑郁症患者的基础rCBF脑灌注显像示额叶、颞叶和右基底节低灌注;激活显像时,额叶、颞叶的低灌注更加明显,并且右顶叶和基底节也有明显的血流灌注减低(图2)。与对照组相比,差异有显著性。
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    讨 论

    非老年期抑郁症和老年期抑郁症发病年龄不同,后者于60岁以后首次发病,一般病程较长,具有缓解和复发倾向,部分患者预后不良,可发展为难治性抑郁症。两者临床表现的差异是否与脑血流灌注显像异常有关呢?本研究显示非老年期抑郁症基础显像额叶、颞叶局部血流灌注减低,认知激活显像额颞叶血流灌注减低更加明显,顶叶血流灌注也减低。老年期抑郁症基础脑显像示双侧额叶、双侧颞叶、右基底节存在局部血流低灌注,激活脑显像示双侧额叶、双侧颞叶、右顶叶、双侧基底节存在局部血流低灌注。

    非老年期抑郁症和老年期抑郁症脑血流灌注显像都显示额颞叶血流灌注减低。而额颞叶的低灌注与抑郁症患者的心境低落、思维阻滞、注意力不集中和记忆力减退密切相关[4,5]。由此推论,两者均以累及额叶、颞叶为主,并伴有其他大脑皮层及皮层下核团的功能损害。

    本研究中,与非老年期抑郁症不同,老年期抑郁
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    表2 非老年期抑郁症组与对照组基础和WCST认知激活rCBF比值 脑区

    基础状态rCBF比值

    t值

    认知激活rCBF比值

    t值

    非老年期抑郁症组(39例)

    非老年期对照组(17例)

    非老年期抑郁症组(25例)

    非老年期对照组(17例)

    右额叶

    0.739±0.042
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    0.782±0.022

    3.98*

    0.745±0.082

    0.806±0.031

    2.90*

    左额叶

    0.719±0.038

    0.768±0.027

    4.90*

    0.733±0.025

    0.809±0.037
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    8.44*

    右顶叶

    0.751±0.020

    0.758±0.015

    1.41

    0.746±0.020

    0.773±0.024

    3.86*

    左顶叶

    0.722±0.033

    0.735±0.015

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    0.713±0.028

    0.754±0.020

    5.13*

    右颞叶

    0.741±0.041

    0.774±0.037

    2.95*

    0.742±0.033

    0.774±0.017

    3.56*
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    左颞叶

    0.718±0.036

    0.761±0.018

    4.78*

    0.703±0.033

    0.771±0.030

    6.80*

    右枕叶

    0.794±0.018

    0.807±0.032

    1.96

, http://www.100md.com     0.787±0.020

    0.817±0.050

    2.02

    左枕叶

    0.791±0.020

    0.804±0.032

    1.86

    0.779±0.054

    0.815±0.048

    2.01

    右基底节

    0.803±0.057
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    0.816±0.038

    0.86

    0.799±0.035

    0.820±0.028

    2.00

    左基底节

    0.795±0.053

    0.814±0.039

    1.34

    0.803±0.029

    0.830±0.045

    2.01
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    右扣带前回

    0.787±0.055

    0.816±0.038

    1.96

    0.784±0.034

    0.818±0.059

    2.01

    左扣带前回

    0.782±0.052

    0.809±0.043

    1.99

    0.774±0.039
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    0.809±0.051

    1.98

    注:与对照组比较,*P<0.01表3 老年期抑郁症组与对照组基础和WCST认知激活rCBF比值 脑区

    基础状态rCBF比值

    t值

    认知激活rCBF比值

    t值

    老年期抑郁症组(18例)

    老年期对照组(21例)

    老年期抑郁症组(12例)

    老年期对照组(18例)
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    右额叶

    0.729±0.020

    0.769±0.043

    3.99**

    0.731±0.024

    0.784±0.033

    5.31**

    左额叶

    0.721±0.040

    0.760±0.046

    2.79**
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    0.726±0.028

    0.780±0.033

    5.40**

    右顶叶

    0.746±0.030

    0.767±0.034

    2.01

    0.742±0.010

    0.770±0.035

    2.69*

    左顶叶
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    0.708±0.051

    0.734±0.027

    2.02

    0.711±0.029

    0.732±0.035

    1.75

    右颞叶

    0.731±0.041

    0.756±0.021

    2.50*

    0.736±0.044

, http://www.100md.com     0.761±0.016

    2.27*

    左颞叶

    0.711±0.037

    0.744±0.026

    3.30**

    0.714±0.042

    0.751±0.032

    2.64*

    右枕叶

    0.775±0.016
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    0.797±0.044

    2.02

    0.786±0.005

    0.807±0.035

    2.02

    左枕叶

    0.779±0.017

    0.800±0.039

    2.01

    0.788±0.027

    0.811±0.035

    1.96
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    右基底节

    0.782±0.043

    0.823±0.059

    2.41*

    0.801±0.007

    0.824±0.027

    2.88*

    左基底节

    0.780±0.036

    0.815±0.063

    1.96
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    0.808±0.012

    0.832±0.030

    2.67*

    右扣带前回

    0.774±0.047

    0.807±0.065

    1.83

    0.780±0.045

    0.795±0.032

    1.07

    左扣带前回

    0.764±0.046
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    0.799±0.073

    1.75

    0.768±0.046

    0.787±0.028

    1.46

    注:与对照组比较,*P<0.05,**P<0.01

    症患者除额颞叶血流灌注减低外,还有基底节脑血流灌注减低。既往研究发现焦虑、快感缺乏、无助感和悲伤都与额颞叶皮层、尾状核的血流灌注和(或)代谢变化密切相关。Mayberg等[6]对难治性单相抑郁症行99Tcm-六甲基丙二胺肟SPECT研究观察到,双侧额叶、颞叶、扣带回和左侧尾状核血流灌注减低。在调节正常情感反应方面,连接边缘系统额叶皮层和基底节的通路起着重要作用。因此,老年期抑郁症与非老年期抑郁症临床表现的不同,可能与前者基底节的血流灌注减低有关。
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    老年痴呆可有抑郁症状,老年期抑郁症也可有“假性痴呆”(pseudo-dementia)[7]。严重抑郁的发病高峰年龄与痴呆在临床上属于相同的年龄范围,并且这2种病人均有躯体主诉或焦虑症状,鉴别诊断有一定困难[7]。但从神经精神科角度而言,区分抑郁与痴呆有其临床重要性,因为抑郁是可以治疗的,而痴呆在目前尚无有效治疗手段[8]。本研究中,老年期抑郁症的额叶、颞叶和基底节具有明显的局部血流灌注减低,后顶叶相关皮质血流灌注正常,与先前报道的老年痴呆的血流灌注减低位于双侧后颞顶部不同。因此,脑血流灌注显像对老年抑郁症和老年痴呆症的鉴别诊断有价值。

    我们选用的神经心理作业是WCST,它可激活额叶皮层,同时也可激活包括颞顶叶在内的一个神经网络[9]。本研究中,抑郁症患者的基础显像就有脑血流灌注异常,激活显像时与抑郁症有关的脑血流灌注异常表现得更加明显。可见,神经激活脑血流灌注显像可提高对抑郁症的诊断信度,对抑郁症的病因学研究及诊断等可能会起到一定作用。
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    图1 非老年抑郁症脑灌注显像。a基础示左额叶轻度低灌注, b认知激活显像示右额叶、左颞

    叶和左顶叶明显低灌注 图2老年期抑郁症脑灌注显像。 a基础示左额叶血流灌注轻度减

    低,b认知激活显像示左额叶低灌注更加明显,且伴左颞叶和左叶血流灌注明显减低

    (本文图1,2见插图页第6页)

    参 考 文 献

    1,Yazici KM, Kapucu O, Eribas B, et al. Assessment of changes in regional cerebral blood flow in patients with major depression using the 99 Tcm-HMPAO single photon emission tomography method. Eur J Nucl Med, 1992, 19:1038-1043.
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    2,Sackeim HA, Prohovnik I, Moeller JR, et al. Regional cerebral blood flow in mood discorders. Arch Gen Psychiatry, 1990, 47:60-70.

    3,赵晋华, 林祥通, 江开达, 等. 抑郁症的基础与认知激活脑SPECT显像. 中华核医学杂志, 1998, 18: 70-72.

    4,Ito H, Kawashima R, Awata S, et al. Hypoperfusion in the limbic system and prefrontal corte in depression: SPECT with anatomic standardization technique. J Nucl Med, 1996, 37:410-414.

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    (收稿日期:1999-09-29), 百拇医药