本文選題：抑郁癥 + 磁共振��； 參考：《昆明醫(yī)科大學》2017年博士論文

【摘要】：抑郁癥是一種與遺傳因素,環(huán)境因素以及心理應激因素均有關的情感障礙,這些因素通過多種途徑導致抑郁癥發(fā)病。然而,由于抑郁癥疾病本身的異質性及復雜性特點,且僅具有中等遺傳度,因此迄今為止研究尚未找到與疾病診斷相關的可靠生物學標記。近十幾年來,腦影像學在抑郁癥的神經(jīng)生物學機制的研究中發(fā)揮越來越重要的作用,并且獲得了一些較一致的結果,逐漸為揭示抑郁癥的發(fā)病機制提供了理論基礎。目前臨床癥狀、遺傳學證據(jù)以及部分影像學證據(jù)提示不同年齡發(fā)病的抑郁癥可能是一種抑郁癥的亞型且與不同的發(fā)病因素有關。然而,目前這些研究中抑郁癥不同年齡發(fā)病的年齡劃界值(cut-offage)并不統(tǒng)一。另一方面,抗抑郁藥物使用、疾病發(fā)作次數(shù)、病程等因素對抑郁癥的腦結構或者腦功能改變均有影響。因此,對首次發(fā)病且未用藥的抑郁癥患者的腦結構或功能改變進行研究,可能可以為抑郁癥發(fā)病的潛在病理機制提供影像學證據(jù)。因此,本研究采用磁共振方法對成年早發(fā)和晚發(fā)抑郁癥患者的腦灰質結構、局部腦功能及功能連接三個方面進行研究,探討不同年齡發(fā)病的成年抑郁癥是否有不同的影像學變化特征,這種變化可能提示不同年齡發(fā)病的抑郁癥有不同的發(fā)病機制。第一部分不同年齡首次發(fā)病且未服藥的成年抑郁癥患者腦灰質體積變化的研究[目的]目前很少有研究針對成年早發(fā)抑郁癥(Early adult onset depression,EOD)和成年晚發(fā)抑郁癥(Later adult onset depression,LOD)的病理機制的研究。本研究想通過腦影像學分析比較EOD和LOD之間的全腦灰質體積(grey matter volume,GMV)是否具有差異,并且該差異能夠區(qū)別EOD和LOD。[方法]通過臨床收集147名首次發(fā)病且未服用藥物的抑郁癥(major depressive disorder,MDD)患者,年齡范圍為18-45歲,將患者按照發(fā)病年齡分為成年早發(fā)抑郁癥組(18-29歲)和成年晚發(fā)抑郁癥組(30-44歲)。收集與患者組年齡,性別相匹配的健康對照(Healthy control,HC)共計130人,并且也根據(jù)上述年齡劃分為分別與EOD和LOD匹配的兩組。所有參與者均完成頭顱磁共振掃描。采用基于體素的形態(tài)學(voxel-basedmorphometry,VBM)方法分析所獲得的磁共振結構數(shù)據(jù)。并將有差異的腦區(qū)體素值與疾病嚴重程度進行相關性分析。[結果]與HC比較,MDD組的頂葉,顳葉,邊緣系統(tǒng),枕葉以及小腦的GMV具有統(tǒng)計學差異。與年輕對照組比較,EOD組的右側梭狀回,右側顳中回以及小腦蚓Ⅲ區(qū)的GMV顯著減小,而右側枕中回的GMV顯著增大。而LOD組的右側海馬GMV比相應對照組顯著減小而左側顳中回GMV比相應對照組顯著增大。當EOD組與LOD組比較,EOD組右側后扣帶回的GMV顯著減小。而兩組患者的右側后扣帶回的GMV與漢密爾頓抑郁量表的評分相關性無統(tǒng)計學意義。[結論]首次發(fā)病未服藥的成年抑郁癥患者的情感環(huán)路相關的GMV與健康對照比較顯著減小。EOD與LOD患者分別與相應的健康對照比較以及這兩組患者之間進行比較均發(fā)現(xiàn)有特征性的GMV減小,表明不同年齡發(fā)病的成年抑郁癥患者可能有不同的病理生理機制。第二部分采用靜息態(tài)fMRI探究首次發(fā)病且未服藥的成年早發(fā)和晚發(fā)抑郁癥的局部一致性變化[目的]前述的研究中通過采用30歲的年齡界值發(fā)現(xiàn)EOD患者和LOD患者之間具有特異性的GMV差異,而既往研究表明腦功能和腦結構的改變可能獨立的與抑郁癥的發(fā)病機制相關。因此本研究想探究當采用同樣年齡劃界值時EOD與LOD患者之間的局部一致性(regional homogeneity,ReHo)是否也具有顯著性差異,而且這種差異能否揭示不同年齡發(fā)病的抑郁癥具有不同的發(fā)病機制。[方法]對前述研究的所有患者進行靜息態(tài)功能磁共振(resting-state functionalMRI)掃描,對獲得的靜息態(tài)磁共振數(shù)據(jù)預處理,經(jīng)過頭動校正后,將水平位移1.5mm和旋轉幅度1.5°的患者剔除,最終有58名EOD患者,62名LOD患者,60名年輕健康對照以及52名年老健康對照進入分析,采用基于體素的方法對受試者的靜息態(tài)數(shù)據(jù)進行ReHo的比較分析。將有差異的腦區(qū)體素值與疾病嚴重程度和病程進行相關性分析。[結果]通過單因素方差分析(ANOVA)發(fā)現(xiàn)四組之間的右側前扣帶回和右側額頂葉區(qū)域的ReHo值具有統(tǒng)計學差異。當EOD組與LOD組患者比較時,EOD組患者的左側楔前葉ReHo值顯著增高,而左側梭狀回的ReHo顯著降低。當與年輕健康對照比較時,EOD患者的右側鋸狀回及右側額頂葉區(qū)域的ReHo值顯著增高。而與年老的健康對照比較時,LOD患者的右側額頂葉區(qū)域的ReHo值也顯著增高。在兩組患者組中進行相關性分析,左側楔前葉與右側梭狀回的ReHo值與漢密爾頓抑郁量表得分以及病程相關性均無統(tǒng)計學意義。[結論]楔前葉及梭狀回的ReHo值異常改變可能是區(qū)分EOD患者和LOD患者的潛在腦區(qū),并且提示不同年齡發(fā)病的成年抑郁癥患者可能有不同的抑郁癥發(fā)病機制。右側額頂葉區(qū)域的ReHo值異常則可能是獨立于發(fā)病年齡而與抑郁癥的診斷相關的潛在腦區(qū)。第三部分首次發(fā)病且未用藥的成年早發(fā)和晚發(fā)抑郁癥患者的腦功能連接差異研究[目的]前述的研究發(fā)現(xiàn)EOD和LOD患者之間后扣帶回(PCC)灰質體積以及楔前葉(PCu)的ReHo值具有差異。由于PCC/PCu是默認網(wǎng)絡(default mode network,DMN)的后部核心節(jié)點區(qū)域,因此本部分以PCu為感興趣區(qū)域,探索是否EOD和LOD患者的功能連接有差異,并且與不同發(fā)病機制相關。[方法]對第二部分獲得的靜息態(tài)磁共振數(shù)據(jù)預處理,剔除由于過度頭動(水平位移1.5mm和旋轉幅度1.5°)的患者,最終有58名EOD患者,62名LOD患者,60名年輕健康對照以及52名年老健康對照進入分析,采用感興趣區(qū)域(region of interest,ROI)的方法,選擇左側楔前葉為種子點(seed region),計算該種子點與全腦的功能連接,并比較各組間與該種子點的功能連接差異。[結果]通過單因素方差分析(ANOVA)發(fā)現(xiàn)四組之間FC具有差異的腦區(qū)涉及雙側額葉,顳葉,基底節(jié),枕葉,頂葉及小腦等廣泛腦區(qū)。與相匹配正常對照比較,EOD患者的左側楔前葉與左側顳中回,左側小腦Ⅸ區(qū),左側小腦Crus1區(qū),右側額中回,右側內側額上回,右側腦島,右側前扣帶回,右側顳中回,右側角回,右側楔前葉的功能連接升高。而與左側額中回,左側中央旁小葉,右側額上回,右側顳下回,右側緣上回,右側中央前回,右側中央后回,右側枕上回的功能連接降低。LOD患者的左側楔前葉與左側眶額部額中回,左側額中回,左側顳下回,左側殼核,左側角回,左側小腦Crus1區(qū),左側小腦Crus2區(qū),右側額上回,右側額中回,右側角回,右側腦干的功能連接升高。左側額上回,右側中央前回,右側中央旁小葉,右側梭狀回,右側海馬旁回,右側顳下回,右側枕中回,右側后扣帶回,右側鋸狀回的功能連接降低。相比于LOD組,EOD組的楔前葉與左側小腦Crus2區(qū),左側小腦Ⅳ-Ⅵ區(qū),左側鋸狀回的功能連接升高。而與右側眶額部額下回,右側眶額部額中回,右側額上回,右側額中回功能連接降低。[結論]PCu與構成DMN的右側腦區(qū)的功能連接異常可能與EOD患者的發(fā)病機制有關,而PCu與DMN相關腦區(qū)的FC呈現(xiàn)前部功能升高和后部功能降低的特點可能與LOD患者的發(fā)病機制有關。EOD與LOD患者的PCu與全腦的FC之間有統(tǒng)計學差異,提示不同年齡發(fā)病的成年抑郁癥患者可能有不同的發(fā)病機制。
[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.

【學位授予單位】：昆明醫(yī)科大學
【學位級別】：博士
【學位授予年份】：2017
【分類號】：R749.4

【參考文獻】

相關期刊論文 前1條

1 朱雪玲;王湘;肖晶;廖堅;姚樹橋;;首發(fā)未服藥抑郁癥靜息態(tài)默認網(wǎng)絡研究[J];中國臨床心理學雜志;2011年02期

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本文編號：1880236