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(fā)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(yè)和社交生活中表現(xiàn)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(jù)世界衛(wèi)生組織 (WHO) 的說法，它是導致殘疾的主要原因。情緒低落、對日?；顒拥呐d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(xiàn)，嚴重影響一個人進行日?；顒拥哪芰?。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?。ㄈ缧难芗膊。┑膸茁试黾佑嘘P、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(fā)育過程中持續(xù)暴露于環(huán)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(zhèn)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(fā)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(jù)抑郁癥的單胺假說，NE、5HT和DA同步發(fā)揮作用，調節(jié)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(jù)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(yǎng)因子(BDNF)調節(jié)。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(fā)作的環(huán)境變化的能力提高。根據(jù)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(fā)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(tǒng)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(xiàn)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(fā)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(fā)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(qū)域（例如海馬體）中發(fā)現(xiàn)的獨特類型的感受態(tài)細胞、腦室下區(qū)和神經結構，并可能自發(fā)地和響應局部信號感應產生神經元。神經發(fā)生 (NG) 被認為需要一組明確的信號線索，以通過周圍環(huán)境在空間和時間上非常協(xié)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(fā)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(fā)生。BDNF 的表達也會刺激神經發(fā)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(tǒng)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(fā)生的調節(jié)方式需要大量工作。 

生長因子、遞質、酶、組織激素、神經調節(jié)劑和抗體預計會被激活的細胞分泌到局部組織環(huán)境中，從而引發(fā)所需的組織反應。在受損的神經元和神經膠質網(wǎng)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(fā)揮作用。這些特性導致創(chuàng)傷和灌注問題（如中風 、局部缺血或神經退行性?。┋煼ǖ陌l(fā)明取得實質性進展。

不出所料，NSCs在精神衛(wèi)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(shù)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(xiàn)神經發(fā)生減少。這進一步意味著神經發(fā)生缺陷可能導致與抑郁癥相關的癥狀，而增強的神經發(fā)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(fā)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(fā)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(tǒng)神經元獲得功能和形態(tài)特性，以整合到現(xiàn)有的神經網(wǎng)絡或替換其他各種已經死亡的腦細胞。

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