不同年龄首次发病且未服药成年抑郁症患者的脑影像学研究

发布时间：2018-05-12 21:32

本文选题：抑郁症 + 磁共振　；参考：《昆明医科大学》2017年博士论文

【摘要】：抑郁症是一种与遗传因素,环境因素以及心理应激因素均有关的情感障碍,这些因素通过多种途径导致抑郁症发病。然而,由于抑郁症疾病本身的异质性及复杂性特点,且仅具有中等遗传度,因此迄今为止研究尚未找到与疾病诊断相关的可靠生物学标记。近十几年来,脑影像学在抑郁症的神经生物学机制的研究中发挥越来越重要的作用,并且获得了一些较一致的结果,逐渐为揭示抑郁症的发病机制提供了理论基础。目前临床症状、遗传学证据以及部分影像学证据提示不同年龄发病的抑郁症可能是一种抑郁症的亚型且与不同的发病因素有关。然而,目前这些研究中抑郁症不同年龄发病的年龄划界值(cut-offage)并不统一。另一方面,抗抑郁药物使用、疾病发作次数、病程等因素对抑郁症的脑结构或者脑功能改变均有影响。因此,对首次发病且未用药的抑郁症患者的脑结构或功能改变进行研究,可能可以为抑郁症发病的潜在病理机制提供影像学证据。因此,本研究采用磁共振方法对成年早发和晚发抑郁症患者的脑灰质结构、局部脑功能及功能连接三个方面进行研究,探讨不同年龄发病的成年抑郁症是否有不同的影像学变化特征,这种变化可能提示不同年龄发病的抑郁症有不同的发病机制。第一部分不同年龄首次发病且未服药的成年抑郁症患者脑灰质体积变化的研究[目的]目前很少有研究针对成年早发抑郁症(Early adult onset depression,EOD)和成年晚发抑郁症(Later adult onset depression,LOD)的病理机制的研究。本研究想通过脑影像学分析比较EOD和LOD之间的全脑灰质体积(grey matter volume,GMV)是否具有差异,并且该差异能够区别EOD和LOD。[方法]通过临床收集147名首次发病且未服用药物的抑郁症(major depressive disorder,MDD)患者,年龄范围为18-45岁,将患者按照发病年龄分为成年早发抑郁症组(18-29岁)和成年晚发抑郁症组(30-44岁)。收集与患者组年龄,性别相匹配的健康对照(Healthy control,HC)共计130人,并且也根据上述年龄划分为分别与EOD和LOD匹配的两组。所有参与者均完成头颅磁共振扫描。采用基于体素的形态学(voxel-basedmorphometry,VBM)方法分析所获得的磁共振结构数据。并将有差异的脑区体素值与疾病严重程度进行相关性分析。[结果]与HC比较,MDD组的顶叶,颞叶,边缘系统,枕叶以及小脑的GMV具有统计学差异。与年轻对照组比较,EOD组的右侧梭状回,右侧颞中回以及小脑蚓Ⅲ区的GMV显著减小,而右侧枕中回的GMV显著增大。而LOD组的右侧海马GMV比相应对照组显著减小而左侧颞中回GMV比相应对照组显著增大。当EOD组与LOD组比较,EOD组右侧后扣带回的GMV显著减小。而两组患者的右侧后扣带回的GMV与汉密尔顿抑郁量表的评分相关性无统计学意义。[结论]首次发病未服药的成年抑郁症患者的情感环路相关的GMV与健康对照比较显著减小。EOD与LOD患者分别与相应的健康对照比较以及这两组患者之间进行比较均发现有特征性的GMV减小,表明不同年龄发病的成年抑郁症患者可能有不同的病理生理机制。第二部分采用静息态fMRI探究首次发病且未服药的成年早发和晚发抑郁症的局部一致性变化[目的]前述的研究中通过采用30岁的年龄界值发现EOD患者和LOD患者之间具有特异性的GMV差异,而既往研究表明脑功能和脑结构的改变可能独立的与抑郁症的发病机制相关。因此本研究想探究当采用同样年龄划界值时EOD与LOD患者之间的局部一致性(regional homogeneity,ReHo)是否也具有显著性差异,而且这种差异能否揭示不同年龄发病的抑郁症具有不同的发病机制。[方法]对前述研究的所有患者进行静息态功能磁共振(resting-state functionalMRI)扫描,对获得的静息态磁共振数据预处理,经过头动校正后,将水平位移1.5mm和旋转幅度1.5°的患者剔除,最终有58名EOD患者,62名LOD患者,60名年轻健康对照以及52名年老健康对照进入分析,采用基于体素的方法对受试者的静息态数据进行ReHo的比较分析。将有差异的脑区体素值与疾病严重程度和病程进行相关性分析。[结果]通过单因素方差分析(ANOVA)发现四组之间的右侧前扣带回和右侧额顶叶区域的ReHo值具有统计学差异。当EOD组与LOD组患者比较时,EOD组患者的左侧楔前叶ReHo值显著增高,而左侧梭状回的ReHo显著降低。当与年轻健康对照比较时,EOD患者的右侧锯状回及右侧额顶叶区域的ReHo值显著增高。而与年老的健康对照比较时,LOD患者的右侧额顶叶区域的ReHo值也显著增高。在两组患者组中进行相关性分析,左侧楔前叶与右侧梭状回的ReHo值与汉密尔顿抑郁量表得分以及病程相关性均无统计学意义。[结论]楔前叶及梭状回的ReHo值异常改变可能是区分EOD患者和LOD患者的潜在脑区,并且提示不同年龄发病的成年抑郁症患者可能有不同的抑郁症发病机制。右侧额顶叶区域的ReHo值异常则可能是独立于发病年龄而与抑郁症的诊断相关的潜在脑区。第三部分首次发病且未用药的成年早发和晚发抑郁症患者的脑功能连接差异研究[目的]前述的研究发现EOD和LOD患者之间后扣带回(PCC)灰质体积以及楔前叶(PCu)的ReHo值具有差异。由于PCC/PCu是默认网络(default mode network,DMN)的后部核心节点区域,因此本部分以PCu为感兴趣区域,探索是否EOD和LOD患者的功能连接有差异,并且与不同发病机制相关。[方法]对第二部分获得的静息态磁共振数据预处理,剔除由于过度头动(水平位移1.5mm和旋转幅度1.5°)的患者,最终有58名EOD患者,62名LOD患者,60名年轻健康对照以及52名年老健康对照进入分析,采用感兴趣区域(region of interest,ROI)的方法,选择左侧楔前叶为种子点(seed region),计算该种子点与全脑的功能连接,并比较各组间与该种子点的功能连接差异。[结果]通过单因素方差分析(ANOVA)发现四组之间FC具有差异的脑区涉及双侧额叶,颞叶,基底节,枕叶,顶叶及小脑等广泛脑区。与相匹配正常对照比较,EOD患者的左侧楔前叶与左侧颞中回,左侧小脑Ⅸ区,左侧小脑Crus1区,右侧额中回,右侧内侧额上回,右侧脑岛,右侧前扣带回,右侧颞中回,右侧角回,右侧楔前叶的功能连接升高。而与左侧额中回,左侧中央旁小叶,右侧额上回,右侧颞下回,右侧缘上回,右侧中央前回,右侧中央后回,右侧枕上回的功能连接降低。LOD患者的左侧楔前叶与左侧眶额部额中回,左侧额中回,左侧颞下回,左侧壳核,左侧角回,左侧小脑Crus1区,左侧小脑Crus2区,右侧额上回,右侧额中回,右侧角回,右侧脑干的功能连接升高。左侧额上回,右侧中央前回,右侧中央旁小叶,右侧梭状回,右侧海马旁回,右侧颞下回,右侧枕中回,右侧后扣带回,右侧锯状回的功能连接降低。相比于LOD组,EOD组的楔前叶与左侧小脑Crus2区,左侧小脑Ⅳ-Ⅵ区,左侧锯状回的功能连接升高。而与右侧眶额部额下回,右侧眶额部额中回,右侧额上回,右侧额中回功能连接降低。[结论]PCu与构成DMN的右侧脑区的功能连接异常可能与EOD患者的发病机制有关,而PCu与DMN相关脑区的FC呈现前部功能升高和后部功能降低的特点可能与LOD患者的发病机制有关。EOD与LOD患者的PCu与全脑的FC之间有统计学差异,提示不同年龄发病的成年抑郁症患者可能有不同的发病机制。
[Abstract]:Depression is an affective disorder associated with genetic, environmental and psychological stress factors. These factors lead to depression in many ways. However, due to the heterogeneity and complexity of the depressive disorder itself and only moderate heritability, so far the study has not been found to be related to the diagnosis of disease. In recent decades, brain imaging has played a more and more important role in the study of neurobiological mechanisms of depression, and has obtained some more consistent results, gradually providing a theoretical basis for revealing the pathogenesis of depression. At present, the clinical symptoms, genetic evidence and some imaging evidence are proposed. Depression may be a subtype of depression and related to different factors. However, the age delimitation value of depression (cut-offage) is not uniform in these studies. On the other hand, the use of antidepressant drugs, the number of episodes of disease, the course of disease, and other factors are related to the brain structure of depression or the brain structure of depression. Therefore, the study of changes in the brain structure or function of the first onset and untreated depressive patients may provide imaging evidence for the underlying pathological mechanism of depression. Therefore, this study uses magnetic resonance (MRI) to determine the gray matter structure and local brain of adults with early and late onset depression. Study on three aspects of functional and functional connection to investigate whether there are different imaging changes in adult depression at different ages. This change may suggest different pathogenesis of depression at different ages. The purpose of this study is to study the pathological mechanism of Early adult onset depression (EOD) and adult late onset depression (Later adult onset depression, LOD). This study was to compare the volume of the whole brain gray matter between EOD and LOD. Differences, and the differences can be distinguished by the EOD and LOD.[methods] by collecting 147 first - onset and non - drug - based depression (major depressive disorder, MDD) patients, aged 18-45 years, divided into adult early depressive group (18-29 years old) and adult late onset depression (30-44 years). The age of the group, the gender matched healthy control (Healthy control, HC) total of 130 people, and were also divided into two groups matched with EOD and LOD according to the age. All participants completed the skull magnetic resonance scan. The magnetic resonance structure data obtained by the voxel based morphology (voxel-basedmorphometry, VBM) method were used to analyze the magnetic resonance structure data. Compared with HC, the GMV of the parietal lobe, the temporal lobe, the marginal system, the occipital lobe and the cerebellum in the MDD group had statistical differences. Compared with the young control group, the right fusiform gyrus, the right temporal gyrus and the GMV in the vermis of the cerebellum were significantly reduced in the EOD group and the right occipital gyrus. The GMV of the right hippocampus in the LOD group was significantly lower than that in the corresponding control group and the left temporal gyrus GMV was significantly higher than that in the corresponding control group. When the EOD group was compared with the LOD group, the GMV of the right posterior cingulate gyrus in the EOD group decreased significantly. The correlation between the GMV in the right posterior cingulate gyrus and the Hamilton depression scale in the two groups of patients was not statistically significant. [Conclusion] the emotional loop related GMV of the first onset untreated adult depressive patients compared with the healthy control significantly reduced the comparison of the.EOD and LOD patients with the corresponding healthy controls, and the comparison of the two groups found the characteristic GMV decrease, indicating that the adult depressive patients who were not in the same age may have Different pathophysiological mechanisms. The second part uses resting state fMRI to explore the first onset and the local conformance changes in early onset and late onset depression. In the previous study, a specific GMV difference was found between EOD patients and LOD patients by using age values at the age of 30, while previous studies showed brain function and The changes in brain structure may be independent of the pathogenesis of depression. Therefore, this study seeks to explore whether there is a significant difference in local consistency (regional homogeneity, ReHo) between EOD and LOD patients when using the same age demarcation value, and whether this difference can reveal different onset of depression at different ages. Disease mechanism. [Methods] all patients in the previous study were scanned with resting state functional magnetic resonance (resting-state functionalMRI). After preprocessing of resting state magnetic resonance data, after head motion correction, the patients with horizontal displacement 1.5mm and 1.5 degrees of rotation were eliminated, the most 58 EOD patients, 62 LOD patients, and 60 young healthy pairs were found. A comparative analysis of the resting state data of the subjects was carried out by a voxel based approach and a comparative analysis of the resting state data of the subjects with a voxel based approach. The correlation between the differences in the brain voxel values and the severity of the disease and the course of the disease was analyzed. [results] the right anterior cingulate gyrus and right between the four groups were found through the single factor analysis of variance (ANOVA). ReHo values in the lateral parietal lobe were statistically different. When compared with the EOD group, the ReHo value of the left anterior lobe of the EOD group was significantly higher and the ReHo in the left fusiform gyrus was significantly lower. When compared with the young health, the ReHo of the right sawing and right frontal lobe regions of the EOD patients was significantly higher. The ReHo value of the right frontal parietal area in the right side of the LOD patients was also significantly higher than that in the healthy control. There was no statistical significance in the correlation analysis between the two groups of patients and the correlation between the ReHo value of the left anterior lobe and the right fusiform gyrus, the score of the Hamilton depression scale and the correlation of the course of the disease. [Conclusion] the abnormal changes in the ReHo value of the anterior and fusiform gyrus may be changed. It is a potential brain region that distinguishes between EOD and LOD patients, and suggests that adult depressive patients at different ages may have different mechanisms of depression. The right frontal parietal region of the ReHo may be a potential brain region independent of the age of onset and the diagnosis of depression. The third part is first and unused. Study on the difference of brain functional connection between early onset and late onset depression [Objective] the previous study found that the volume of gray matter in the posterior cingulate gyrus (PCC) and the ReHo value of the anterior lobe (PCu) between EOD and LOD were different. Because PCC/PCu was the core node of the default network (default mode network, DMN), this part of this part was PCu. Interest areas, exploring whether the functional connections between EOD and LOD patients were different and related to different pathogenesis. [Methods] the second part of the resting state magnetic resonance data preprocessing, excluding the patients with excessive head movement (horizontal displacement 1.5mm and 1.5 degrees of rotation), finally had 58 EOD patients, 62 LOD patients, and 60 young healthy controls. And 52 old healthy controls entered the analysis, using the region of interest (ROI) method, selecting the left anterior lobe as the seed point (seed region), calculating the functional connection between the seed point and the whole brain, and comparing the difference of functional connection between each group and the seed point. [results] four groups were found by single factor analysis of variance (ANOVA). FC with different brain regions involved bilateral frontal lobe, temporal lobe, basal ganglia, occipital lobe, parietal lobe and cerebellum. Compared with normal control, the left anterior lobe of EOD patients and left temporal gyrus, left cerebellum IX area, left cerebellum Crus1 area, right frontal gyrus, right medial frontal gyrus, right insula, right anterior cingulate gyrus, right temporal middle In the right angular gyrus, the functional connection of the right anterior lobe was elevated, but with the left middle frontal gyrus, the left central paraleal lobule, the right frontal gyrus, right inferior temporal gyrus, right superior margin, right central anterior gyrus, right posterior central gyrus, and right occipital gyrus to lower the left lateral wedge and the left orbital frontal frontal gyrus, left middle frontal gyrus, left side, left side, left side, left side of the left side, left middle frontal gyrus, left side, left side, left side, left lateral frontal gyrus, left lateral frontal gyrus, left lateral frontal gyrus, left side of.LOD patients. Lower temporal gyrus, left putamen, left cerebellum Crus1, left cerebellum Crus2, right frontal gyrus, right frontal gyrus, right frontal gyrus, right frontal gyrus, right frontal gyrus, right central frontal gyrus, right paracentral lobule, right fusiform gyrus, right parahippocampal gyrus, right lateral temporal gyrus, right right occipital gyrus, right posterior cingulate gyrus The functional connection of the right sawing gyrus was reduced. Compared to the LOD group, the anterior lobe of the EOD group increased with the left cerebellum Crus2 region, the left cerebellum IV - VI region, the left sawing gyrus, and the right orbital frontal gyrus, the right orbital frontal frontal gyrus, the right frontal gyrus, and the right middle frontal gyrus. [conclusion]PCu and DMN right brain brain The dysfunction of the functional connection in the region may be associated with the pathogenesis of EOD patients, while the FC in the PCu and DMN related brain regions is characterized by higher anterior function and lower posterior function, which may be associated with the pathogenesis of LOD patients with a statistically significant difference between the PCu and the whole brain in the.EOD and LOD patients. There are different mechanisms of disease.

【学位授予单位】：昆明医科大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R749.4

【参考文献】