Cited by 386Neurogenesis and neuroplasticity mechanismsTreatment of Major DepressionStress Responses and Cortisol

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The current state of the neurogenic theory of depression and anxiety

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Miller, Bradley R, Hen, René·2015·Current Opinion in Neurobiology

DOI 10.1016/j.conb.2014.08.012PMC PMC4293252

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Abstract

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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Authors: Miller, B. R., & Hen, R.
Affiliations: New York State Psychiatric Institute (US)
Corresponding author: Hen, René
ORCID: Miller, Bradley R
Hen, René
Venue: Current Opinion in Neurobiology
Publisher: Elsevier BV
Published: 2015-02
Volume: 30
Pages: 51-58
ISSN: 0959-4388 (ISSN-L)
DOI: 10.1016/j.conb.2014.08.012
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
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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