The current state of the neurogenic theory of depression and anxiety

• Diverse animal models of depression and anxiety have impaired neurogenesis.
• Neurogenesis is consistently boosted by antidepressants in animal models when animals are stressed.
• Ablation of neurogenesis in animal models impairs cognitive functions relevant to depression, but only a minority of studies find that ablation causes depression or anxiety.
• Recent human neuroimaging and postmortem studies are consistent with the neurogenic theory, but they are indirect.
• A novel drug developed based on the neurogenic theory is promising in animal models.

Newborn neurons are continuously added to the adult hippocampus. Early studies found that adult neurogenesis is impaired in models of depression and anxiety and accelerated by antidepressant treatment. This led to the theory that depression results from impaired adult neurogenesis and restoration of adult neurogenesis leads to recovery. Follow up studies yielded a complex body of often inconsistent results, and the veracity of this theory is uncertain. We propose five criteria for acceptance of this theory, we review the recent evidence for each criterion, and we draw the following conclusions: Diverse animal models of depression and anxiety have impaired neurogenesis. Neurogenesis is consistently boosted by antidepressants in animal models only when animals are stressed. Ablation of neurogenesis in animal models impairs cognitive functions relevant to depression, but only a minority of studies find that ablation causes depression or anxiety. Recent human neuroimaging and postmortem studies are consistent with the neurogenic theory, but they are indirect. Finally, a novel drug developed based on the neurogenic theory is promising in animal models.