重度抑郁癥 (MDD)，俗稱抑郁癥，是一種使人衰弱的疾病，影響全球約3.8%的人口，其中5.0%是成年人，5.7%是60歲以上的人。MDD不同于常見的情緒變化和由于灰質和白質（包括額葉、海馬體、顳葉、丘腦、紋狀體和杏仁核）的細微變化而導致的短暫情緒反應。如果它以中等或嚴重的強度發生，它可能對一個人的整體健康有害。它會使一個人在個人、職業和社交生活中表現不佳而痛苦不堪。

一、簡介

重度抑郁癥 (MDD) 被認為是最常見的精神疾病，根據世界衛生組織 (WHO) 的說法，它是導致殘疾的主要原因。情緒低落、對日常活動的興趣下降、內疚、失去快樂、注意力難以集中、自卑、睡眠困難和食欲改變是 MDD 的一些癥狀。

這些問題可能會長期存在或反復出現，嚴重影響一個人進行日常活動的能力。在最壞的情況下，抑郁癥會導致自殺念頭。抑郁癥與患其他嚴重疾病（如心血管疾病）的幾率增加有關、中風、阿爾茨海默病、癲癇、糖尿病和癌癥。抑郁癥狀在老年人中更常見，但這是由于與衰老相關的因素造成的，包括身體殘疾、認知缺陷、社會經濟缺陷和其他因素。難治性抑郁癥 (TRD) 可由發育過程中持續暴露于環境壓力源引起。幾乎所有的抗抑郁藥都以相同的方式起作用，并在整個生命周期內有效治療嚴重的MDD。

然而，抗抑郁治療有許多不良副作用，包括鎮靜、頭痛、血壓下降、失眠、體重增加、消化不良、情緒激動、口干、腹瀉和性功能障礙。這通常會導致患者依從性差，導致抑郁癥狀復發和更高的自殺風險。

2. 抑郁癥的神經化學：單胺假說

去甲腎上腺素 (NE)、血清素（5-羥色胺，5HT）和多巴胺 (DA) 失調與抑郁癥的病理變化有關（圖1）。根據抑郁癥的單胺假說，NE、5HT和DA同步發揮作用，調節情緒和情緒。在情緒低落時，觀察到這三種單胺的失調，以及細胞外5HT水平低于平均水平。據報道，與年齡匹配的對照組相比，抑郁癥患者的尿液、血液和腦脊液 (CSF) 中的單胺類和代謝物含量較低。

3. 抑郁癥的生長因子

有幾種與抑郁癥狀相關的生物學因素，如中所示。與抑郁行為相關的神經回路中的突觸可塑性受腦源性神經營養因子(BDNF)調節。有趣的是，壓力引起的大腦結構和突觸可塑性損傷可能會被BDNF上調逆轉，從而導致認知的靈活性和適應可能刺激抑郁發作的環境變化的能力提高。根據目前的研究，在抑郁癥受試者中，血液中的BDNF水平較低，并且隨著抗抑郁治療的增加而增加，如圖2。研究表明，應激誘導的表觀遺傳變化可導致抑郁癥。對MDD顳葉結構研究的兩項薈萃分析表明，復發性抑郁癥患者的海馬體較小。此外，無論使用何種藥物，升高的BDNF血漿水平都與更好的治療結果有關。

在分子、遺傳、表觀遺傳、細胞和系統水平上有多種生物學原因。這些原因會導致臨床抑郁癥，并且可能會出現多種癥狀，這些癥狀可能因人而異。

4. 神經干細胞與抑郁癥

近年來，神經干細胞移植引起了人們的興趣，大量發表的文獻闡明成人大腦維持多能NSCs，這與大腦的舊教條形成鮮明對比，大腦通常是不變的和靜止的器官，缺乏再生的靈活性。憑借其最普遍接受的顯著特征，NSCs也被歸于所謂的組織

干細胞 ，具有在特定條件下保持未分化而沒有概述表型的能力、分裂和增殖（自我更新）的能力，以及在神經發生開始時分化成神經元、少突膠質細胞和星形膠質細胞等后代的能力。它們是在成年哺乳動物大腦的“神經源性”區域（例如海馬體）中發現的獨特類型的感受態細胞、腦室下區和神經結構，并可能自發地和響應局部信號感應產生神經元。神經發生 (NG) 被認為需要一組明確的信號線索，以通過周圍環境在空間和時間上非常協調的方式傳遞給神經源性細胞，以激活干細胞或祖細胞以發育新的神經元，此外，眾所周知的調制器，損傷被認為足以激活神經發生。BDNF 的表達也會刺激神經發生。NSC通常是從成人腦組織中提取的，包括死后腦組織，并成為增加或恢復受中樞神經系統相關疾病影響的腦組織質量和功能的重要候選者。NSC在體外進行克隆擴增、基因操作或刺激以轉化CNS細胞譜系。了解成人神經發生的調節方式需要大量工作。 

生長因子、遞質、酶、組織激素、神經調節劑和抗體預計會被激活的細胞分泌到局部組織環境中，從而引發所需的組織反應。在受損的神經元和神經膠質網絡中，新賦能的細胞及其后代可以作為功能增強劑和支架“修復劑”發揮作用。這些特性導致創傷和灌注問題（如中風 、局部缺血或神經退行性病）療法的發明取得實質性進展。

不出所料，NSCs在精神衛生保健方面的前景正在引起激烈爭論。許多精神疾病可能具有遺傳變異以及大多數未知的特定細胞和解剖相關性。

在抑郁癥中，海馬體中經常會出現神經發生減少。這進一步意味著神經發生缺陷可能導致與抑郁癥相關的癥狀，而增強的神經發生可以介導抗抑郁作用并緩解癥狀。

然而，在建立這種雙向概念的完全合法性之前，必須首先調和關于神經發生在緩解抑郁癥中的作用的各種相互矛盾的報告。成人海馬神經發生的激活導致神經體細胞后代轉化為成熟的CNS神經元。然后，這些中樞神經系統神經元獲得功能和形態特性，以整合到現有的神經網絡或替換其他各種已經死亡的腦細胞。

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