【作者】 袁辉；

【导师】 祁吉；

【作者基本信息】 天津医科大学 ， 影像医学与核医学， 2008， 硕士

【摘要】 目的:利用功能磁共振成像(fMRI)联合使用经典心理学范式(Stroop字色干扰任务)探讨抑郁症病人认知功能障碍的神经机制;利用磁共振波谱成像(MRS)评价抑郁症病人是否存在认知相关脑功能区代谢物的异常改变,以及MRS代谢指标与经典认知测试——威斯康星卡片分类测试(WSCT)之间是否具有相关性,从代谢水平探讨抑郁症病人认知功能障碍的神经病理生理学机制。材料与方法:21例临床确诊为抑郁症的病人,其中首次发作抑郁症病人12例(2组或首发抑郁组),复发抑郁症病人(发作次数2～3次)9例(3组或复发抑郁组),另有12例与抑郁组年龄、性别匹配的正常志愿者(1组或正常对照组)纳BOLD-fMRI部分研究。利用组块设计的Stroop任务联合fMRI对所有受试者进行研究,刺激采用视觉呈现。Stroop任务包括两组:①字色一致的颜色命名任务;②字色不一致的颜色命名任务。每组任务包括4个刺激组块和5个对照组块,刺激组块和对照组块交替出现。利用AFNI对所有受试者的功能成像数据进行处理,记录每组任务中,各组受试者的激活脑区及激活体素情况。MRI检查完毕后,对受试者进行Stroop的行为学测试,分别记录测试的总反应时间以及错误数。此外,22例临床确诊为抑郁症的病人,如上也分为三组,其中1组12人,2组12人,3组10人,纳入MRS部分本项研究。所有受试者在行MRI检查前进行威斯康星卡片分类测试(WSCT),记录测试结果。所有受试者均行双侧前额叶及前扣带回的单体素氢质子波谱—点分辨自旋回波波谱序列(PRESS)扫描,记录各代谢物曲线下面积与Cr的比值,即NAA/Cr、Cho/Cr、mIns/Cr、Glx/Cr。结果:①行为学结果:对反应时间而言,正常对照组、首发抑郁组和复发抑郁组进行字色不一致的颜色命名的反应时间均长于字色一致的颜色命名的反应时间,差别存在统计学意义(P＜0.01)。在字色一致的颜色命名任务中,首发抑郁组、复发抑郁组虽然较正常对照组的反应时间有增加的趋势,但差别无统计学意义;在字色不一致的颜色命名任务中,首发抑郁组、复发抑郁组的反应时间长于正常对照组,差别有统计学意义(P＜0.01),但复发抑郁组与首发抑郁组反应时间的差别无统计学意义。对错误数而言,常对照组、首发抑郁组和复发抑郁组进行字色不一致的颜色命名的错误数多于字色一致的颜色命名的错误数,差别存在统计学意义(P＜0.01)。在字色一致的颜色命名任务中,首发抑郁组、复发抑郁组较正常对照组存在错误增多的趋势,但其差别均无统计学意义;然而,在字色不一致的颜色命名任务中,首发抑郁组、复发抑郁组均较正常对照组的错误数增多,其差别有统计学意义(P＜0.01),而复发抑郁组与首发抑郁组之间错误数的差别无统计学意义。②激活功能脑区及体素:正常对照组执行字色一致的颜色命名任务时,激活了双侧额上回、额中回、额下回和双侧颞顶叶等多个脑区;执行不一致的颜色命名任务时,上述脑区多数激活体素增加,其中右侧额上回、左侧额下回、左侧顶上小叶及左侧楔前叶激活体素增加,差别有统计学意义(P＜0.05),此外还出现了扣带回及前扣带回的激活。首发抑郁组及复发抑郁组病人执行字色一致的颜色命名任务时,激活了双侧额上回、额中回、额下回,左额内侧回,双侧扣带回和前扣带回,以及双侧颞顶叶等多个脑区;在执行字色不一致的颜色命名任务时,两组均可见左侧额叶脑区激活体素增加,其中首发抑郁组左侧额中回激活体素的增加有统计学意义(P＜0.05),复发抑郁组左侧额上回、左侧额中回激活体素的增加有统计学意义(P＜0.05),此外,首发抑郁组病人还有双侧楔前叶,复发抑郁组病人还有左侧顶下小叶、右侧楔叶及楔前的激活体素增加,差别均有统计学意义(P＜0.05)。对各组受试者执行字色一致及字色不一致的颜色命名任务时,对称激活脑区体素的比较结果,正常对照组执行字色一致和字色不一致的颜色命名任务时,双侧对称激活脑区激活体素差别均无统计学意义(P＞0.05)。首发抑郁组和复发抑郁组病人在字色一致的颜色命名任务时,额中回的激活体素左侧均大于右侧,差别有统计学意义(P＜0.05),字色不一致的颜色命名任务时,首发抑郁组病人额中回激活体素左侧大于右侧,差别有统计学意义(P＜0.01),复发抑郁组病人额中回及额下回激活体素左侧均大于右侧,差别具有统计学意义(P＜0.05)。③与正常对照相比,复发抑郁组病人双侧前额叶Glx/Cr减低(P＜0.01)、mIns/Cr升高(P＜0.05),首发抑郁组病人双侧前额叶Glx/Cr减低(P＜0.05),右侧前额叶mIns/Cr升高(P＜0.05)。而除左侧前额叶mIns/Cr复发抑郁组病人高于首发抑郁组病人(P＜0.05),其他代谢指标在首发和复发抑郁组之间无统计学差异。④与正常对照组相比,首发抑郁组及复发抑郁组病人均存在WCST中完成分类总数(Response Administered,RA)(P=0.01)、持续错误数(Perseverative Errors,PE)(P＜0.01)和非持续错误数(Non Perseverative Errors,NPE)增加(P＜0.05),但WCST结果在首发抑郁组和复发抑郁组之间的差别无统计学意义。⑤首发抑郁组病人右侧前额叶Glx/Cr与WCST中持续错误数呈负相关(r=-0.744,P＜0.05),复发抑郁组病人双侧前额叶Glx/Cr与WCST中持续错误数均呈负相关(r=-0.790,P＜0.05;r=-0.710,P＜0.05)。结论:①行为学和fMRI研究证实首发及复发抑郁症病人均存在选择注意及执行控制功能障碍。扣带回—前额叶皮层—顶叶网络异常以及双侧前额叶功能失衡共同构成了首发及复发抑郁症病人认知障碍的神经病理生理学基础。②行为学及功能成像均未发现复发抑郁症病人比首发抑郁症病人存在更严重的认知功能障碍(可能与本研究纳入的复发抑郁症病人发作次数较少有关)。③与正常对照组相比,抑郁症病人存在双侧前额叶的异常代谢变化,复发抑郁组病人表现为双侧前额叶Glx/Cr减低,mIns/Cr升高;首发抑郁组病人表现为双侧前额叶Glx/Cr减低,右侧前额叶mIns/Cr升高。除左侧前额叶mIns/Cr复发抑郁组病人高于首发抑郁组病人,其他代谢指标在首发和复发抑郁组病人之间的差异均不显著。④与正常人相比,首发抑郁组及复发抑郁组病人均存在WCST中完成分类总数、持续错误数和非持续错误数增加,但在首发抑郁组和复发抑郁组病人之间差别无统计学意义。⑤首发抑郁组病人右侧前额叶Glx/Cr与WCST中持续错误数呈负相关,复发抑郁组病人双侧前额叶Glx/Cr与WCST中持续错误数呈负相关。提示谷氨酸能系统异常可能是抑郁症病人认知障碍的病理生理学基础。更多还原

【Abstract】 Objective:To explore neural basis of cognitive function impairment in both first-episode and recurrent patients with depression using blood oxygenation level dependent functional magnetic resonance imaging(BOLD-fMRI);to evaluate whether the patients with depression have brain metabolite changes using MRS,and to assess the correlation between abnormal metabotite ratio of MRS and WSCT which has been considered as the most classic cognitive test,and to explore the neuropathophysiologic mechanism of depression.Materials and Methods:21 patients with depression,in whom there were 12 first-episode patients(group 2 or first-episode group)and 9 recurrent patients(group 3 or recurrent group)and 12 age- and gander-matched healthy volunteers(group 1 or normal controls)were included in this study.Stroop task in Chinese character was used as target stimulus,which included two kinds of task:①congruous color-naming task②incongruous color-naming task.Block-design fMRI was used to acquire resource data,including 4 stimulus blocks and 5 control blocks,each block was alternatively present.Imaging analysis was performed using analysis of functional neuroimaging(AFNI),all the activating voxels in each task were recorded respectively.After fMRI examinations were over,behavior tests of Stroop interference were performed for all subjects.Overall reaction time and error numbers were recorded respectively.Further more,22 patients with depression,in whom there were 12 first-episode patients and 10 recurrent patients and 12 age- and gander-matched healthy volunteers were included in this study.All subjects performed WCST before MR examination.MRS data in bilateral prefrontal lobe and cingulated cortex were acquired by point-resovled echo spin spectroscopy(PRESS) sequence of single voxel 1-hydrogen MRS.The software automatically completed metabolite content measurement,giving the ratio of all metabolite using Cr as a reference,including NAA/Cr,Cho/Cr,mIns/Cr,Glx/Cr.Results:①Behavior performance results:Subjects of three groups all need more reaction time when performed incongruous color-naming task than that of congruous color-naming task(P＜0.01).In the congruous color-naming task,subjects of three groups showed no significant difference in reaction time,while in the incongruous color-naming task patients both with first-episode and recurrent depression need more reaction time(P＜0.01).Subjects of three groups all had more errors when performed incongruous color-naming task than that of congruous color-naming task(P＜0.01).Both first-episode and recurrent depressive patients had more errors in performing incongruous color-naming task than health controls(P＜0.01),and without significant differecens in performing congruous color-naming task.There were no significant differences in reaction time as well as in error numbers in patients both with first-episode and recurrent depression.②Activated cerebral functional cortex and activated voxets:When normal controls performed congruous color-naming task,bilateral superior frontal gyrus,bilateral middle frontal gyrus,bilateral inferior frontal gyrus,bilateral parietal and temporal lobes were activated;while when they performed incongruous color-naming task,the activated voxels that mentioned above in congruous color-naming task were increased,especially in right superior frontal gyrus,left inferior frontal gyrus,left superior parietal lobe and left precuneus(P＜0.05),and there were also some other cortex were activated,including cingulate gyrus and anterior cingulated gyrus. Bilateral superior frontal gyrus,bilateral middle frontal gyrus,bilateral inferior frontal gyrus,left medial frontal lobe,bilateral cingulate gyrus and anterior cingulated gyrus, bilateral parietal and temporal lobes were activated in patients both with first-episode and recurrent depression when they performed congruous color-naming task;when performed incongruous color-naming task,larger activated voxel in left prefrontal lobe than that of congruous color-naming task in both first-episode and recurrent depression,and the voxel in left middle frontal gyrus increased significantly in patients with first-episode depression(P＜0.05),while the voxel in left superior frontal gyrus and left middle frontal gyrus increased significantly in patients with recurrent depression(P＜0.05).except for that,first-episode depressive patients showed increased activated voxel in bilateral precuneus(P＜0.05),and recurrent patients showed increased activated voxel in left inferior parietal lobule,right precuneus and left cuneus(P＜0.05).We compared activated symmetrical functional cortex in each group during each task.In normal controls,the activated voxels of symmetrical functional cortex in both task were no significant differences (P＞0.05).In congruous color-naming task,the activated voxets in left middle frontal lobe were larger than those of right side in both first-episode and recurrent depressive patients(P＜0.05).In congruous color-naming task,first-episode depressive patients showed meddile frontal lobe activated voxels larger in left side than those of right side(P＜0.01),and recurrent depressive patients showed both meddile and inferior frontal lobe activated voxels larger in left side than those of right side(P＜0.05).③Compared with normal controls,decreased Glx/Cr(P＜0.01)and increased mIns/Cr (P＜0.05)in both bilateral prefrontal lobes were detected in patients with recurrent depression,while,decreased Glx/Cr(P＜0.05)in bilateral prefrontal lobes and increased mIns/Cr(P＜0.05)in right side were detected in first-episode patients.There were no significant difference between first-episode and recurrent depressive patients, except that the recurrent patients shows higher mIns/Cr in left prefrontal lobe.④Compared with normal controls,the depressive patients had higher RA(P=0.01),PE (P＜0.01)and NPE(P＜0.05)in WCST,but the was no significant difference between first-episode and recurrent depressive patients.⑤Glx/Cr of right prefrontal lobe correlated negatively with PE of WCST significantly(r=-0.744,P＜0.05)in the first-episode patients with depression.Glx/Cr of bilateral prefrontal lobes all correlated negatively with PE of WCST significantly(r=-0.79,P＜0.05;r=-0.71, P＜0.01)in the recurrent patients with depression.Conclusion:①behavior data and fMRI results have demonstrated that the patients both with first-episode and recurrent depression all have cognitive impairment.The abnormal brain network of cingulated-prefrontal cortex-parietal lobe and the functional imbalance of bilateral prefrontal lobe are the neural basis of cognitive impairment of patients with depression.②there is no evidence both in behavior data and fMRI results shows that cognitive impairment of patients with recurrent depression more sever than those of with first-episode ones.③compared with normal controls,depressive patients have an abnormal metabolite changes in bilateral prefrontal lobes.Recurrent patients are present with decreased Glx/Cr and increased mIns/Cr in bilateral prefrontal lobes,and first-episode patients are present with decreased Glx/Cr in bilateral prefrontal lobes and increased mIns/Cr in right prefrontal lobe.Except for the higher mIns/Cr in recurrenct patients than in fist-episode patients,there are no significant metabolite difference between these two groups.④compared with normal controls,patients both with first-episode and recurrent depression all have higher RA,PE and NPE in WCST,but there were no significant difference between first-episode and recurrent depressive patients.⑤Glx/Cr of right prefrontal lobe correlated negatively with PE of WCST significantly in the first-episode patients with depression.Glx/Cr of bilateral prefrontal lobes all correlated negatively with PE of WCST significantlyin the recurrent patients with depression.These all indicate that glutamatergic systems dysregulation may be the pathophysiology basis of cognitive impairement of pantients with depression.更多还原