The current state of the neurogenic theory of depression and anxiety
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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.
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Increased hippocampal dendritic atrophy and cell death as well as reduced LTP and BDNF expression have been reported in MDD.
“increased hippocampal dendritic atrophy and cell death as well as reduced LTP and BDNF expression have also been reported (Miller and Hen 2015; Pittenger 2013).”
From Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression (2018) · cites this paper as Miller and Hen 2015
The section “Evidence that AHN is altered in depression and anxiety > Human” (page unavailable) reports smaller dentate gyri and fewer dentate gyrus granule cells in patients with depression or anxiety disorders. It does not establish dendritic atrophy or cell death as the cause, and our copy does not report reduced LTP or BDNF expression in MDD. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn MDD, structural changes are often observed in the course of this pathology.
“In MDD, neuroimaging and post-mortem studies in humans indicate that structural changes are often observed in the course of this pathology.”
From Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression (2018) · cites this paper as Miller and Hen 2015
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- Authors
- Miller, B. R., & Hen, R.
- Affiliations
- New York State Psychiatric Institute (US)
- Corresponding author
- Hen, René
- Venue
- Current Opinion in Neurobiology
- Publisher
- Elsevier BV
- Published
- 2015-02
- Volume
- 30
- Pages
- 51-58
- ISSN
- 0959-4388 (ISSN-L)
- PMC
- PMC4293252
- OpenAlex
- W1977184712
- Cited by
- 386
- References
- 75
- Citations by year
- 2026: 15 · 2025: 16 · 2024: 24 · 2023: 23 · 2022: 29 · 2021: 46 · 2020: 40 · 2019: 46 · 2018: 32 · 2017: 38 · 2016: 42 · 2015: 33 · 2014: 1
- FWCI
- 3.95
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Current Opinion in Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Leon Levy Foundation
- National Institute for Mental Health (R25: MH086466-03, R37 MH068542)
- National Institute on Aging (R01 AG043688)
- National Institute of Neurological Disorders and Stroke (R01NS081203-01A1)
- NYSTEM (C029157)
- Hope for Depression Research Foundation (RGA 11-024)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- adult hippocampal neurogenesis, depression, anxiety, antidepressants, animal models of depression, stress, cognitive impairment, postmortem studies, neuroimaging
- MeSH terms
- Animals, Antidepressive Agents, Anxiety, Depression, Disease Models, Animal, Hippocampus, Humans, Neurons, Neurogenesis
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