Of Duman’s many influential findings, the finding that long-term treatment with antidepressant drugs produces an increase in neurogenesis in the subgranular zone of the adult hippocampus may be one of the most enduring and far-reaching. This novel discovery and his decades of continued research in the field led to a new hypothesis about the mechanism of action of antidepressants, providing a critical step in our understanding of the neurotrophic hypothesis of depression and synaptic plasticity. It is now accepted that antidepressant treatments can oppose and even reverse the effects of stress on the brain and on newly born hippocampal cells, possibly via neurotrophic factors, which Duman had continued to explore. Furthermore, ablation studies have shown preclinically that hippocampal neurogenesis may be necessary for some of the clinical effects of antidepressant drugs. Duman’s laboratory continued to interrogate neurotrophins and synaptic plasticity, demonstrating that newer clinically approved antidepressant compounds also affect neurogenesis and synaptic plasticity. In this review, we summarize Duman’s original findings and discuss the current state of the field of neurogenesis with respect to animal models and human studies and the implications of those findings on the field of drug discovery.

在杜曼的许多有影响力的发现中，长期使用抗抑郁药物治疗会增加成年海马颗粒下区神经发生的发现可能是最持久和影响最深远的发现之一。这一新发现和他在该领域数十年的持续研究导致了关于抗抑郁药作用机制的新假设，为我们理解抑郁症和突触可塑性的神经营养假设迈出了关键一步。现在人们普遍认为，抗抑郁治疗可以对抗甚至逆转压力对大脑和新生海马细胞的影响，可能是通过杜曼继续探索的神经营养因子。此外，消融研究在临床前表明，海马神经发生可能是抗抑郁药物的某些临床效果所必需的。Duman 的实验室继续研究神经营养因子和突触可塑性，证明更新的临床批准的抗抑郁化合物也会影响神经发生和突触可塑性。在这篇综述中，我们总结了 Duman 的原始发现，并讨论了神经发生领域在动物模型和人体研究方面的现状，以及这些发现对药物发现领域的影响。