ArticleMolecular psychiatry2011
Antidepressants increase human hippocampal neurogenesis by activating the glucocorticoid receptor.
Article in Molecular psychiatry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 199 papers, 5 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
199 citing papers in PubMed, 5 syntheses or guidelines pooled it, 434 citations in OpenAlex.
- From placenta to the foetus: a systematic review of in vitro models of stress- and inflammation-induced depression in pregnancy.Molecular psychiatry · 2025Pooled it
- Acute and long-term effects of adolescence stress exposure on rodent adult hippocampal neurogenesis, cognition, and behaviour.Molecular psychiatry · 2023Pooled it
- Transcriptomic Studies of Antidepressant Action in Rodent Models of Depression: A First Meta-Analysis.International journal of molecular sciences · 2022Pooled it
- Systems Approach to Identify Common Genes and Pathways Associated with Response to Selective Serotonin Reuptake Inhibitors and Major Depression Risk.International journal of molecular sciences · 2019Pooled it
- A systems approach to stress, stressors and resilience in humans.Behavioural brain research · 2015Pooled it
- Effects of Cortisol Administration on Resting-State Functional Connectivity in Women with Depression.Psychiatry research. Neuroimaging · 2024Trial
- Omega-3 polyunsaturated fatty acids protect against inflammation through production of LOX and CYP450 lipid mediators: relevance for major depression and for human hippocampal neurogenesis.Molecular psychiatry · 2021Trial
- Transcriptomic signatures of treatment response to the combination of escitalopram and memantine or placebo in late-life depression.Molecular psychiatry · 2021Trial
- Slowed Processing Speed Disrupts Patient Expectancy in Late Life Depression.The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry · 2021Trial
- Cortisol effects on brain functional connectivity during emotion processing in women with depression.Journal of affective disorders · 2021Trial
- Trial
- Role for the kinase SGK1 in stress, depression, and glucocorticoid effects on hippocampal neurogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2013Trial
- Candidate genes expression profile associated with antidepressants response in the GENDEP study: differentiating between baseline 'predictors' and longitudinal 'targets'.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2013Trial
- Effect of Sertraline on Fetoplacental Growth Parameters and Placental Transporter Gene Expression in Rats.International journal of molecular sciences · 2026Article
- Remission is insufficient: predictors and mechanistic models of recurrence in late-life depression.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Review
- Validation in Drosophila of the in silico predicted clomipramine as repurposable for SOD1-ALS.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- The dietary ligands, omega-3 fatty acid endocannabinoids and short-chain fatty acids prevent cytokine-induced reduction of human hippocampal neurogenesis and alter the expression of genes involved in neuroinflammation and neuroplasticity.Molecular psychiatry · 2025Article
- Social Determinants of Health and Early Brain Development.Pediatric clinics of North America · 2025Review
- Boosting Neurogenesis as a Strategy in Treating Alzheimer's Disease.International journal of molecular sciences · 2025Review
- MARK2 regulates Golgi apparatus reorientation by phosphorylation of CAMSAP2 in directional cell migratio.eLife · 2025Article
139 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
Antidepressants increase adult hippocampal neurogenesis in animal models, but the underlying molecular mechanisms are unknown. In this study, we used human hippocampal progenitor cells to investigate the molecular pathways involved in the antidepressant-induced modulation of neurogenesis. Because our previous studies have shown that antidepressants regulate glucocorticoid receptor (GR) function, we specifically tested whether the GR may be involved in the effects of these drugs on neurogenesis. We found that treatment (for 3-10 days) with the antidepressant, sertraline, increased neuronal differentiation via a GR-dependent mechanism. Specifically, sertraline increased both immature, doublecortin (Dcx)-positive neuroblasts (+16%) and mature, microtubulin-associated protein-2 (MAP2)-positive neurons (+26%). This effect was abolished by the GR-antagonist, RU486. Interestingly, progenitor cell proliferation, as investigated by 5'-bromodeoxyuridine (BrdU) incorporation, was only increased when cells were co-treated with sertraline and the GR-agonist, dexamethasone, (+14%) an effect which was also abolished by RU486. Furthermore, the phosphodiesterase type 4 (PDE4)-inhibitor, rolipram, enhanced the effects of sertraline, whereas the protein kinase A (PKA)-inhibitor, H89, suppressed the effects of sertraline. Indeed, sertraline increased GR transactivation, modified GR phosphorylation and increased expression of the GR-regulated cyclin-dependent kinase-2 (CDK2) inhibitors, p27(Kip1) and p57(Kip2). In conclusion, our data suggest that the antidepressant, sertraline, increases human hippocampal neurogenesis via a GR-dependent mechanism that requires PKA signaling, GR phosphorylation and activation of a specific set of genes. Our data point toward an important role for the GR in the antidepressant-induced modulation of neurogenesis in humans.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.