- 學位論文
以形態與聯結體分析法評估憂鬱症患者之大腦結構與網路異常
Assessment of abnormal brain anatomies and networks in major depressive disorder using morphometric and connectome analyses
摘要
憂鬱症是備受關注社會問題，根據世界衛生組織的調查發現，每十個人就有一個人因為憂鬱症而備受困擾。重度憂鬱症患者的自我傷害行為可能會導致死亡的風險增加。神經影像造影的技術對人類大腦上的探討上在近年來備受矚目，且結構及功能性的影像分析技術扮演著十分重要的角色。因此，本實驗研究的目的就是希望透過更全方位的影像分析來對憂鬱症患者的大腦與結構進行完善的了解。 我們收集了16位憂鬱症患者以及30為健康受試者，他們分別接受1.5T MRI (Magnetic resonance imaging)之靜息態磁振造影(Resting-state functional magnetic resonance imaging, rs-fMRI)以及T1權重造影(T1 weighted imaging, T1WI)，及擴散磁振造影(Diffusion MRI)，接著進行功能性連結(Functional connectivity)、低頻振福(Amplitude low frequency fluctuations, ALFF)、區域同質性(Regional homogeneity, ReHo)、圖論(Graph theoretical)、基於體素之形態學測量(Voxel-based morphometry, VBM)、基於體素之統計分析(Voxel-based statistical analysis, VBA)、頂點形狀分析(Vertex-wise shape analysis)、以及憂鬱量表分數與影像的相關性分析。 憂鬱症患者在雙側的杏仁核(Amygdala)、海馬迴(Hippocampus)、島腦(Insula)、丘腦(Thalamus)以及視覺區(Visual area)、運動區(Motor area)和預設模式神經網路(Default mode network, DMN)皆出現功能性連結下降的情形，且在被殼(Putamen)以及島腦出現ALFF訊號與憂鬱程度的高度負相關性，前額葉出現高度正相關性。除此之外，憂鬱症患者在雙側的丘腦、胼胝體(Corpus callosum)、前額葉及運動輔助區(Supplementary motor area, SMA)出現ReHo上升的結果，但在顳葉(Temporal lobe)則出現下降的情形。而圖論分析的結果發現憂鬱症患者大腦網路的局部功能分隔度(Local segregation)在結構性網路出現上升而功能性網路出現下降的趨勢。結構影像分析的結果呈現憂鬱症患者於胼胝體以及海馬迴、杏仁核出現顯著的體積下降，且海馬迴與杏仁核的體積與憂鬱程度亦成性高度負相關性。同時，憂鬱症患者之左側杏仁核形狀和正常受試者相比之下呈現顯著差異。杏仁核的功能與負面情緒調節和接受情緒刺激相關，憂鬱症患者出現的海馬迴體積下降可能與Hypothalamic–pituitary–adrenal axis (HPA axis)機制相關，而前額葉涉及的功能十分的廣闊，其中包含情緒回應、抑制能力等等，憂鬱症患者在結構所出現的型態以及功能差異可能會造成其在處理功能上遇到困難。 我們透過全方位的影像技術分析，發現憂鬱症患者在結構功能與型態出現顯著地下降差異。本次研究結果的發現若能在未來臨床上作為診斷參考或許可以對憂鬱症患者的臨床表現有更完整的了解。
並列摘要
Major depressive disorder (MDD) is a public health problem characterized by negative thoughts, sadness, and feelings of worthlessness and hopelessness. It can occur in individuals of different genders, ages, and backgrounds. This disease is not only associated with a significantly increased risk of suicide, but it is also a leading cause of disability worldwide. According to an investigation conducted by the World Health Organization (WHO) in 2012, MDD is the third leading global cause of disease burden, and its ranking is expected rise to first place by 2030. Neuroimaging techniques, including advanced structural and functional imaging analysis methods, have been used to explore the human brain in recent years. We used an extensive range of analytical methods to identify the structural and functional brain abnormalities in MDD patients. Forty-six participants were recruited, including 16 MDD patients and 30 age- and sex-matched healthy controls. All participants were clinically diagnosed by psychiatrists and using the 17-item Hamilton Depression Rating Scale (HAMD). All images were acquired using a 1.5 Tesla MRI (Signa HDxt, GE Medical System, USA) with an 8-channel head coil. All participants received resting-state functional magnetic resonance imaging (rs-fMRI), T1-weighted imaging and diffusion MRI scans. We used a full range of analytical methods and report the complete results for patients with depression. Data analysis included assessments of functional connectivity, amplitude low-frequency fluctuations (ALFF), voxel-based morphometry (VBM), and regional homogeneity (ReHo), graph theoretical analysis, voxel-based statistical analysis (VBA) and vertex-wise shape analysis. Correlations between the images and HAMD scores were also calculated. The results of analysis revealed differences between the MDD and control groups. First, we found decreased functional connectivity in the MDD brains and a highly negative correlation between the HAMD score and ALFF in the putamen and insula. Second, we found increased ReHo in the bilateral thalamus, corpus callosum, frontal lobe, and the supplementary motor area (SMA), while reduced ReHo was found in the in the temporal lobe. Third, we observed a change in local segregation in the MDD patients. We also found a decrease in the size of the amygdala and changes in the hippocampus volume and shape in the MDD patients, along with a highly negative correlation between the HAMD score and the hippocampus and amygdala volumes. The amygdala plays an important role in effective emotional regulation and processing of emotional stimuli in humans. Reductions in hippocampus volume are associated with dysregulation of the hypothalamic–pituitary–adrenal axis (HPA axis). The frontal lobe is thought to be associated with the regulation of emotional responses and is linked to a variety of cognitive functions. Abnormalities within these structures have profound consequences on cognitive function. Our results may reveal good candidate imaging markers for clinical diagnosis. They present potential structural and functional substrates for future research efforts and improve the understanding of the underlying pathophysiology of depression.