The neurogenesis hypothesis of affective and anxiety disorders: are we mistaking the scaffolding for the building?
The neurogenesis hypothesis of affective and anxiety disorders: are we mistaking the scaffolding for the building?
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DOI：
10.1016/j.neuropharm.2011.09.003
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发表时间：
2012-01
影响因子：
4.7
通讯作者：
Eisch, Amelia J.
中科院分区：
文献类型：
--
作者：
Petrik, David;Lagace, Diane C.;Eisch, Amelia J.
假设是搭在建筑物前面的脚手架，然后在建筑物完工时拆除。它们对工人来说是不可缺少的;但你千万不要把脚手架误认为是建筑物。歌德。情感障碍的神经发生假说-在其最简单的形式-假设，在出生后海马齿状回神经元的生成参与了重性抑郁症（MDD）的病因和治疗效果。这一假说成立于20世纪90年代，但它是建立在早期对海马体、血清素和MDD的广泛研究基础上的。它已经经历了几个增长阶段，由自然界中相关和因果关系的发现所推动。最近，这一假设也被扩大到包括与焦虑症的潜在相关性，如创伤后应激障碍（PTSD）。正如任何假设一样，它已经受到了考验和挑战，有时甚至是激烈的考验和挑战。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--神经发生减少导致抑郁或焦虑--一般来说是如何被拒绝的。我们还回顾了这些疾病的治疗，如抗抑郁药，是否依赖于完整的神经发生的疗效，以及抗抑郁药的神经发生依赖性和非依赖性作用的存在的争议。此外，我们回顾了该假设对压力反应，PTSD和恢复力的神经生物学的影响，并强调了我们自己的工作，表明成人产生的神经元在功能上对社会压力的行为反应很重要。最后，我们强调如何在转基因小鼠技术的进步，啮齿动物的行为分析，以及我们对神经发生过程的理解将使我们能够完善我们的结论，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”，我们可能会忽视在诊所中产生转化影响的机会。
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.
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