首发未服药青年重性抑郁症脑网络连接的磁共振成像研究
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摘要
目的：从脑网络的角度,探讨抑郁症相关的特异性脑结构和脑功能的生物学标记。
(1)应用基于神经束的空间统计学方法(tract-based spatial statistics, TBSS)处理首发未服药青年重性抑郁症患者的弥散张量数据(diffusion tensor imaging, DTI),探讨抑郁症脑白质结构连接的改变及其与临床症状之间的关系。
(2)采用静息态功能磁共振技术,以默认网络(default mode network, DMN)研究为入手点,探讨患者抑郁症静息态脑功能连接的异常改变；在此基础上,进一步研究患者DMN与冗思、自传体记忆等抑郁症状之间的关系。
方法：
(1)对30例首发未服药青年重性抑郁症患者和30例与抑郁症组按性别、年龄和教育程度匹配的健康对照者,进行全脑DTI扫描。应用TBSS方法比较两组脑白质图像的各向异性分数(fractional anisotropy,FA),寻找有显著性差异的脑白质区域。进一步对抑郁症患者的脑白质结构图与抑郁症严重程度、病程和发病年龄等临床症状进行相关分析。
(2)对35例首发未服药青年重性抑郁症患者和35例与抑郁症组按性别、年龄和教育程度匹配的健康对照者,进行静息态功能磁共振数据采集。采用独立成分分析方法(independent component analysis, ICA)对数据进行处理,检测患者组与对照组DMN功能连接有显著性差异的脑区。进一步引入认知情绪调节问卷冗思因子得分(CERQ-rumination)和自传体记忆(autobiographical memory, AM)得分等行为学数据,探讨其与抑郁症患者DMN影像学数据之间的相关性。
结果：
(1)与正常对照组相比,抑郁症组的左侧内囊前肢、右侧海马旁回、左侧后扣带回白质的FA值显著低于正常组(p＜0.05,t＞3,多重校正).患者组左侧内囊的FA值与抑郁症状严重程度得分呈负相关。未发现抑郁症组比正常人组FA值高的脑区。
(2)与正常对照组相比,抑郁症组的DMN前部如背内侧前额叶/腹侧前扣带回(dorsal MPFC/ventral ACC).腹内侧前额叶(ventral MPFC)和内侧眶额回(medial orbital PFC)功能连接升高,而DMN后部如后扣带/楔前叶(posterior cingulate cortex/precuneus, PCC/precuneus)、角回(Angular gyrus, AG)功能连接显著降低(p＜0.05,t＞3,FDR校正)。相关分析表明,DMN前部的ventral MPFC和ventralACC的功能连接与CERQ-rumination得分呈正相关；而DMN后部的precuneus和AG的功能连接与过度概括化记忆得分(overgeneral autobiographical memory, OAM)呈负相关。
结论：
(1)首发未服药青年重性抑郁症存在脑白质微结构连接的异常,异常的纤维束主要涉及前额叶-子皮层和边缘系统-子皮层等与认知和情感调节关系较密切的神经环路。这些神经环路的白质结构异常导致大脑皮层和皮层下组织连接损害,这可能是理解抑郁症神经病理基础的关键。此外,该研究进一步证实前额叶、海马和扣带回是抑郁症白质损害的关键区域,并且这种损害在抑郁症发病早期就已经存在。
(2)首发未服药青年重性抑郁症存在静息态DMN功能连接异常。DMN异常表现为“前高后低”的模式,即前部区域如MPFC和ACC功能连接增强,并与冗思得分呈正相关；后部区域如后precuneus和AG功能连接降低,与过度概括化记忆得分呈负相关。本研究提示静息态DMN功能连接障碍可能是导致抑郁症冗思倾向和自传体记忆损害的病理基础之一,这对解析冗思和自传体记忆的神经生理机制具有重要的意义。
Objective
The aim of the study is to explore the possible changes in brain structural and functional connection in first-episode, treatment-naive young adults with major depressive disorder (MDD), in order to investigate the disease-specific biological makers and to provide new evidences for the understanding the mechamism and diagnosis of MDD.
(1) to explore structural integrity of white matter by means of diffusion tensor imaging and the correlationship with the depressive symptoms in first-episode, treatment-naive young adults with MDD.
(2) to explore resting-state functional connectivity of default mode network and the correlationship with the depressive symptoms in first-episode, treatment-naive young adults with MDD.
Methods
(1) DTI was performed in 30 first-episode, treatment-naive young adult patients with MDD and 30 healthy controls matched for age, gender and education. A whole-brain statistical comparison method called tract-based spatial statistics (TBSS) was used to analyze the data. The white matter difference between the patients and the controls was examined. Then the the severity of depressive symptoms, age at onset of illness and illness duration were introduced to examine their relationship with white matter of depressive patients.
(2) We analyzed the resting-state fMRI data from 35 first-episode, treatment-naive young adults with MDD and 35 age-, gender-and education-matched healthy controls. A method called by independent component analysis (ICA) was used to analyze the resting-state data and the rule of goodness-of-fit was used to choose the independent component. The difference of default mode network (DMN) between the patients and the controls was examined. Then rumination and autobiographical memory were introduced to examine their relationship with the DMN of the depressive patients.
Results
(1) Compared with healthy controls, patients with MDD showed decreased fractional anisotropy (FA) values in three white matter (WM) tracts:the left anterior limb of the internal capsule, the right parahippocampal gyrus and the left posterior cingulate cortex. Further analysis revealed that FA values in the left anterior limb of the internal capsule were negatively correlated with the severity of depressive symptoms. No regions showed higher FA in MDD patients than in controls.
(2) Patients with MDD exhibited higher levels of rumination and autobiographical memory than the controls. We observed increased functional connectivity in the anterior medial cortex region [especially the medial prefrontal cortex (MPFC) and anterior cingulate cortex (ACC)], and decreased functional connectivity in the posterior medial cortex region [especially the posterior cingulate cortex/precuneus (PCC/precuneus)] in MDD patients compared with the controls. Within the depressed group, the increased functional connectivity in anterior medial cortex correlated positively with rumination score, while the decreased functional connectivity in posterior medial cortex correlated negatively with OGM score.
Conclusions
The MDD showed the abnormal WM microstructral integrity and resting-state DMN.
(1) The present results support the hypothesis that altered WM integrity, especially in the cortical-subcortical neural circuit, may contribute to the pathophysiology of MDD. Furthermore, these findings provide novel evidence that microstructural abnormalities in WM may occur early in the course of depression.
(2) We reported a dissociation between anterior and posterior functional connectivity in resting-state DMNs of first-episode, treatment-naive young adults with MDD. Rumination may be mediated by increased functional connectivity in anterior medial regions whereas overgeneral autobiographical memory (OGM) may be mediated by decreased functional connectivity in posterior medial regions of the resting-state DMN. These results provided new evidence for the importance of the DMN in the pathophysiology of MDD and suggested abnormal DMN activity may be an MDD trait.
(1)应用基于神经束的空间统计学方法(tract-based spatial statistics, TBSS)处理首发未服药青年重性抑郁症患者的弥散张量数据(diffusion tensor imaging, DTI),探讨抑郁症脑白质结构连接的改变及其与临床症状之间的关系。
(2)采用静息态功能磁共振技术,以默认网络(default mode network, DMN)研究为入手点,探讨患者抑郁症静息态脑功能连接的异常改变；在此基础上,进一步研究患者DMN与冗思、自传体记忆等抑郁症状之间的关系。
方法：
(1)对30例首发未服药青年重性抑郁症患者和30例与抑郁症组按性别、年龄和教育程度匹配的健康对照者,进行全脑DTI扫描。应用TBSS方法比较两组脑白质图像的各向异性分数(fractional anisotropy,FA),寻找有显著性差异的脑白质区域。进一步对抑郁症患者的脑白质结构图与抑郁症严重程度、病程和发病年龄等临床症状进行相关分析。
(2)对35例首发未服药青年重性抑郁症患者和35例与抑郁症组按性别、年龄和教育程度匹配的健康对照者,进行静息态功能磁共振数据采集。采用独立成分分析方法(independent component analysis, ICA)对数据进行处理,检测患者组与对照组DMN功能连接有显著性差异的脑区。进一步引入认知情绪调节问卷冗思因子得分(CERQ-rumination)和自传体记忆(autobiographical memory, AM)得分等行为学数据,探讨其与抑郁症患者DMN影像学数据之间的相关性。
结果：
(1)与正常对照组相比,抑郁症组的左侧内囊前肢、右侧海马旁回、左侧后扣带回白质的FA值显著低于正常组(p＜0.05,t＞3,多重校正).患者组左侧内囊的FA值与抑郁症状严重程度得分呈负相关。未发现抑郁症组比正常人组FA值高的脑区。
(2)与正常对照组相比,抑郁症组的DMN前部如背内侧前额叶/腹侧前扣带回(dorsal MPFC/ventral ACC).腹内侧前额叶(ventral MPFC)和内侧眶额回(medial orbital PFC)功能连接升高,而DMN后部如后扣带/楔前叶(posterior cingulate cortex/precuneus, PCC/precuneus)、角回(Angular gyrus, AG)功能连接显著降低(p＜0.05,t＞3,FDR校正)。相关分析表明,DMN前部的ventral MPFC和ventralACC的功能连接与CERQ-rumination得分呈正相关；而DMN后部的precuneus和AG的功能连接与过度概括化记忆得分(overgeneral autobiographical memory, OAM)呈负相关。
结论：
(1)首发未服药青年重性抑郁症存在脑白质微结构连接的异常,异常的纤维束主要涉及前额叶-子皮层和边缘系统-子皮层等与认知和情感调节关系较密切的神经环路。这些神经环路的白质结构异常导致大脑皮层和皮层下组织连接损害,这可能是理解抑郁症神经病理基础的关键。此外,该研究进一步证实前额叶、海马和扣带回是抑郁症白质损害的关键区域,并且这种损害在抑郁症发病早期就已经存在。
(2)首发未服药青年重性抑郁症存在静息态DMN功能连接异常。DMN异常表现为“前高后低”的模式,即前部区域如MPFC和ACC功能连接增强,并与冗思得分呈正相关；后部区域如后precuneus和AG功能连接降低,与过度概括化记忆得分呈负相关。本研究提示静息态DMN功能连接障碍可能是导致抑郁症冗思倾向和自传体记忆损害的病理基础之一,这对解析冗思和自传体记忆的神经生理机制具有重要的意义。
Objective
The aim of the study is to explore the possible changes in brain structural and functional connection in first-episode, treatment-naive young adults with major depressive disorder (MDD), in order to investigate the disease-specific biological makers and to provide new evidences for the understanding the mechamism and diagnosis of MDD.
(1) to explore structural integrity of white matter by means of diffusion tensor imaging and the correlationship with the depressive symptoms in first-episode, treatment-naive young adults with MDD.
(2) to explore resting-state functional connectivity of default mode network and the correlationship with the depressive symptoms in first-episode, treatment-naive young adults with MDD.
Methods
(1) DTI was performed in 30 first-episode, treatment-naive young adult patients with MDD and 30 healthy controls matched for age, gender and education. A whole-brain statistical comparison method called tract-based spatial statistics (TBSS) was used to analyze the data. The white matter difference between the patients and the controls was examined. Then the the severity of depressive symptoms, age at onset of illness and illness duration were introduced to examine their relationship with white matter of depressive patients.
(2) We analyzed the resting-state fMRI data from 35 first-episode, treatment-naive young adults with MDD and 35 age-, gender-and education-matched healthy controls. A method called by independent component analysis (ICA) was used to analyze the resting-state data and the rule of goodness-of-fit was used to choose the independent component. The difference of default mode network (DMN) between the patients and the controls was examined. Then rumination and autobiographical memory were introduced to examine their relationship with the DMN of the depressive patients.
Results
(1) Compared with healthy controls, patients with MDD showed decreased fractional anisotropy (FA) values in three white matter (WM) tracts:the left anterior limb of the internal capsule, the right parahippocampal gyrus and the left posterior cingulate cortex. Further analysis revealed that FA values in the left anterior limb of the internal capsule were negatively correlated with the severity of depressive symptoms. No regions showed higher FA in MDD patients than in controls.
(2) Patients with MDD exhibited higher levels of rumination and autobiographical memory than the controls. We observed increased functional connectivity in the anterior medial cortex region [especially the medial prefrontal cortex (MPFC) and anterior cingulate cortex (ACC)], and decreased functional connectivity in the posterior medial cortex region [especially the posterior cingulate cortex/precuneus (PCC/precuneus)] in MDD patients compared with the controls. Within the depressed group, the increased functional connectivity in anterior medial cortex correlated positively with rumination score, while the decreased functional connectivity in posterior medial cortex correlated negatively with OGM score.
Conclusions
The MDD showed the abnormal WM microstructral integrity and resting-state DMN.
(1) The present results support the hypothesis that altered WM integrity, especially in the cortical-subcortical neural circuit, may contribute to the pathophysiology of MDD. Furthermore, these findings provide novel evidence that microstructural abnormalities in WM may occur early in the course of depression.
(2) We reported a dissociation between anterior and posterior functional connectivity in resting-state DMNs of first-episode, treatment-naive young adults with MDD. Rumination may be mediated by increased functional connectivity in anterior medial regions whereas overgeneral autobiographical memory (OGM) may be mediated by decreased functional connectivity in posterior medial regions of the resting-state DMN. These results provided new evidence for the importance of the DMN in the pathophysiology of MDD and suggested abnormal DMN activity may be an MDD trait.
引文
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