The DOI matches its Crossref record; 197 of the 198 references it cites were found in a registry or an index, and 1 are not checked yet.
Neuroactive Steroids and GABAergic Involvement in the Neuroendocrine Dysfunction Associated With Major Depressive Disorder and Postpartum Depression
Open accessAbstract
Stress and previous adverse life events are well-established risk factors for depression. Further, neuroendocrine disruptions are associated with both major depressive disorder (MDD) and postpartum depression (PPD). However, the mechanisms whereby stress contributes to the underlying neurobiology of depression remains poorly understood. The hypothalamic-pituitary-adrenal (HPA) axis, which mediates the body’s neuroendocrine response to stress, is tightly controlled by GABAergic signaling and there is accumulating evidence that GABAergic dysfunction contributes to the impact of stress on depression. GABAergic signaling plays a critical role in the neurobiological effects of stress, not only by tightly controlling the activity of the HPA axis, but also mediating stress effects in stress-related brain regions. Deficits in neuroactive steroids and neurosteroids, some of which are positive allosteric modulators of GABAA receptors (GABAARs), such as allopregnanolone and THDOC, have also been implicated in MDD and PPD, further supporting a role for GABAergic signaling in depression. Alterations in neurosteroid levels and GABAergic signaling are implicated as potential contributing factors to neuroendocrine dysfunction and vulnerability to MDD and PPD. Further, potential novel treatment strategies targeting these proposed underlying neurobiological mechanisms are discussed. The evidence summarized in the current review supports the notion that MDD and PPD are stress-related psychiatric disorders involving neurosteroids and GABAergic dysfunction.
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“The pathophysiology of PPD is likely multifactorial,26,27 with evidence supporting a role for disruption of perinatal γ-aminobutyric acid (GABA) signaling, the major inhibitory signaling pathway of the central nervous system.28”
From Effect of Zuranolone vs Placebo in Postpartum Depression (2021) · cites this paper as [28]
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Neurosteroids as novel antidepressants and anxiolytics: GABA-A receptors and beyond
Zorumski, C. F., Paul, S. M., Covey, D. F., & Mennerick, S. (2019) · Neurobiology of Stress · doi:10.1016/j.ynstr.2019.100196 · Cited by 305
Effect of Zuranolone vs Placebo in Postpartum Depression
Deligiannidis, K. M., Meltzer-Brody, S., Gunduz-Bruce, H., Doherty, J., Jonas, J., Li, S., Sankoh, A. J., Silber, C., Campbell, A. D., Werneburg, B., et al. (2021) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2021.1559 · Cited by 277
Brexanolone for postpartum depression: A meta-analysis of randomized controlled studies
Zheng, W., Cai, D.-B., Zheng, W., Sim, K., Ungvari, G. S., Peng, X.-J., Ning, Y., Wang, G., & Xiang, Y. (2019) · Psychiatry Research · doi:10.1016/j.psychres.2019.07.006 · Cited by 223
Neuroprotective Potentials of Flavonoids: Experimental Studies and Mechanisms of Action
Bellavite, P. (2023) · Antioxidants · doi:10.3390/antiox12020280 · Cited by 235
Poromaa, I. S., Comasco, E., Sumner, R. L., & Eileen Luders, A. (2020) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2020.100856 · Cited by 217
Metadata
- Authors
- Maguire, J.
- Affiliations
- Tufts University (US)
- Corresponding author
- Maguire, Jamie
- ORCID
- Maguire, Jamie
- Venue
- Frontiers in Cellular Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2019-03-08
- Volume
- 13
- Pages
- 83-83
- ISSN
- 1662-5102 (ISSN-L)
- PMC
- PMC6418819
- OpenAlex
- W2921588725
- Cited by
- 113
- References
- 197
- Citations by year
- 2026: 13 · 2025: 13 · 2024: 14 · 2023: 15 · 2022: 6 · 2021: 17 · 2020: 24 · 2019: 10
- FWCI
- 1.65
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Cellular Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Institutes of Health (NS102937, AA026256)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- neurosteroids, GABAergic neurotransmission, GABAA receptor, major depressive disorder, postpartum depression, neuroendocrine dysfunction, hypothalamic-pituitary-adrenal axis, stress, allopregnanolone, positive allosteric modulators, life events
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