Department of Psychiatry, UT Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9070, USA.
Neuropharmacology. 2012 Jan;62(1):21-34. doi: 10.1016/j.neuropharm.2011.09.003. Epub 2011 Sep 19.
Hypotheses are scaffoldings erected in front of a building and then dismantled when the building is finished. They are indispensable for the workman; but you mustn't mistake the scaffolding for the building. Johann Wolfgang von Goethe. The neurogenesis hypothesis of affective disorders - in its simplest form - postulates that the generation of neurons in the postnatal hippocampal dentate gyrus is involved in the etiology and treatment efficacy of major depressive disorder (MDD). The hypothesis was established in the 1990s but was built on a broad foundation of earlier research on the hippocampus, serotonin and MDD. It has gone through several growth phases fueled by discoveries both correlative and causative in nature. Recently, the hypothesis has also been broadened to also include potential relevance for anxiety disorders, like post-traumatic stress disorder (PTSD). As any hypothesis should be, it has been tested and challenged, sometimes vigorously. Here we review the current standing of the neurogenesis hypothesis of affective and anxiety disorders, noting in particular how a central postulate - that decreased neurogenesis results in depression or anxiety - has, in general, been rejected. We also review the controversies on whether treatments for these disorders, like antidepressants, rely on intact neurogenesis for their efficacy, and the existence of neurogenesis-dependent and -independent effects of antidepressants. In addition, we review the implications that the hypothesis has for the response to stress, PTSD, and the neurobiology of resilience, and highlight our own work showing that adult-generated neurons are functionally important for the behavioral response to social stress. We conclude by emphasizing how advancements in transgenic mouse technology, rodent behavioral analyses, and our understanding of the neurogenesis process will allow us to refine our conclusions and perform ever more specific experiments. Such scrutiny is critical, since if we "mistake the scaffolding for the building" we could overlook opportunities for translational impact in the clinic. This article is part of a special Issue entitled 'Anxiety and Depression'.
假说好比建筑物前的脚手架，在建筑物完工后便被拆除。对于建筑工人来说，脚手架不可或缺；但你不能将脚手架误认为是建筑物。
约翰·沃尔夫冈·冯·歌德。情感障碍的神经发生假说——其最简单的形式——假定，产后海马齿状回神经元的产生与重性抑郁障碍（MDD）的病因和治疗效果有关。该假说于 20 世纪 90 年代建立，但它建立在广泛的关于海马体、5-羟色胺和 MDD 的早期研究基础之上。它经历了几个增长阶段，这些阶段是由相关性和因果性的发现推动的。最近，该假说也被扩展到包括创伤后应激障碍（PTSD）等焦虑障碍的潜在相关性。像任何假说一样，它已经经过了测试和挑战，有时还非常激烈。在这里，我们回顾了情感和焦虑障碍的神经发生假说的现状，特别注意到一个中心假设——即神经发生减少导致抑郁或焦虑——总体上已被否定。我们还回顾了关于这些疾病的治疗方法（如抗抑郁药）是否依赖于完整的神经发生来发挥疗效，以及抗抑郁药是否存在神经发生依赖和非依赖的作用。此外，我们还回顾了该假说对压力反应、创伤后应激障碍和神经弹性的神经生物学的影响，并强调了我们自己的工作，表明成年产生的神经元对于社会压力的行为反应具有重要的功能。最后，我们强调了转基因小鼠技术、啮齿动物行为分析以及我们对神经发生过程的理解的进步将如何使我们能够完善结论并进行更具体的实验。这种审查至关重要，因为如果我们“将脚手架误认为是建筑物”，我们可能会忽略临床转化的机会。本文是一个题为“焦虑和抑郁”的特刊的一部分。
