Adult Neurogenesis and Antidepressant Treatment: The Surprise Finding by Ron Duman and the Field 20 Years Later

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 neuro -genesis 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.