Cited by 115Stress Responses and CortisolMaternal Mental Health During Pregnancy and PostpartumNeuroscience and Neuropharmacology Research

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Neuroactive Steroids and GABAergic Involvement in the Neuroendocrine Dysfunction Associated With Major Depressive Disorder and Postpartum Depression

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Maguire, Jamie·2019·Frontiers in Cellular Neuroscience

DOI 10.3389/fncel.2019.00083PMC PMC6418819

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Abstract

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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FIGURE 1 Risk factors and models of MDD and PPD. Previous adverse life events and chronic stress are known risk factors for the development of both MDD and PPD and have been associated with neuroendocrine dysfunction and altered neurosteroid levels which are thought to contribute to the underlying neurobiology of these disorders. In experimental models, hormone withdrawal, chronic stress, and chronic exposure to exogenous corticosterone have been used to model MDD and PPD and is associated with similar neuroendocrine disruption and altered neurosteroid levels.CC BY · PubMed Central

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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)
DOI: 10.3389/fncel.2019.00083
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: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
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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Neuroactive Steroids and GABAergic Involvement in the Neuroendocrine Dysfunction Associated With Major Depressive Disorder and Postpartum Depression

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