The DOI matches its Crossref record; 75 of the 75 references it cites were found in a registry or an index.
The current state of the neurogenic theory of depression and anxiety
Open accessAbstract
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 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
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“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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Cites
Diagnostic and Statistical Manual of Mental Disorders
Williams, J. B. W., & First, M. B. (2013) · Oxford University Press eBooks · doi:10.1093/acrefore/9780199975839.013.104 · Cited by 109,845
Kessler, R. C., Berglund, P., Demler, O., Jin, R., Koretz, D., Merikangas, K. R., Rush, A. J., Walters, E. E., & Wang, P. S. (2003) · JAMA · doi:10.1001/jama.289.23.3095 · Cited by 7,988
Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants
Santarelli, L., Saxe, M., Gross, C., Surget, A., Battaglia, F., Dulawa, S., Weisstaub, N., Lee, J., Duman, R., Arancio, O., et al. (2003) · Science · doi:10.1126/science.1083328 · Cited by 4,321
Self-citationFerrari, A. J., Charlson, F. J., Norman, R. E., Patten, S. B., Freedman, G., Murray, C. J. L., Vos, T., & Whiteford, H. A. (2013) · PLoS Medicine · doi:10.1371/journal.pmed.1001547 · Cited by 3,115
Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus
Malberg, J. E., Eisch, A. J., Nestler, E. J., & Duman, R. S. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-24-09104.2000 · Cited by 3,111
Dynamics of hippocampal neurogenesis in adult humans
Spalding, K. L., Bergmann, O., Alkass, K., Bernard, S., Salehpour, M., Huttner, H. B., Boström, E., Westerlund, I., Vial, C., Buchholz, B. A., et al. (2013) · Cell · doi:10.1016/j.cell.2013.05.002 · Cited by 1,841
Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation
Sahay, A., Scobie, K. N., Hill, A. S., O'Carroll, C. M., Kheirbek, M. A., Burghardt, N. S., Fenton, A. A., Dranovsky, A., & Hen, R. (2011) · Nature · doi:10.1038/nature09817 · Cited by 1,567
Self-citationDiagnostic and Statistical Manual of Mental Disorders
Davey, G. (2013) · Encyclopedia of Women in Today's World · doi:10.4135/9781412995962.n207 · Cited by 1,485
Adult hippocampal neurogenesis buffers stress responses and depressive behaviour
Snyder, J. S., Soumier, A., Brewer, M., Pickel, J., & Cameron, H. A. (2011) · Nature · doi:10.1038/nature10287 · Cited by 1,473
Gould, E., Tanapat, P., McEwen, B. S., Flügge, G., & Fuchs, E. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.6.3168 · Cited by 1,395
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Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants
Duman, R. S., Aghajanian, G. K., Sanacora, G., & Krystal, J. H. (2016) · Nature Medicine · doi:10.1038/nm.4050 · Cited by 1,750
Adult Neurogenesis in the Hippocampus: From Stem Cells to Behavior
Gonçalves, J. T., Schafer, S. T., & Gage, F. H. (2016) · Cell · doi:10.1016/j.cell.2016.10.021 · Cited by 1,122
Marx, W., Penninx, B. W. J. H., Solmi, M., Furukawa, T. A., Firth, J., Carvalho, A. F., & Berk, M. (2023) · Nature Reviews Disease Primers · doi:10.1038/s41572-023-00454-1 · Cited by 910
The Role of Neural Plasticity in Depression: From Hippocampus to Prefrontal Cortex
Liu, W., Ge, T., Leng, Y., Pan, Z., Fan, J., Yang, W., & Cui, R. (2017) · Neural Plasticity · doi:10.1155/2017/6871089 · Cited by 640
Luczynski, P., McVey Neufeld, K.-A., Oriach, C. S., Clarke, G., Dinan, T. G., & Cryan, J. F. (2016) · International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyw020 · Cited by 632
“Neurogenesis, the generation of new neurons, is a key process involved in memory formation, stress responsivity, and antidepressant treatment efficacy (Snyder et al., 2011; Marín-Burgin and Schinder, 2012; Miller and Hen, 2015).”
Background
Metadata
- 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
- 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 (medical) › 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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