Neurobiological and neuropsychiatric effects of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS)

Maninger, Nicole; Wolkowitz, Owen M.; Reus, Victor I.; Epel, Elissa S.; Mellon, Synthia H.

doi:10.1016/j.yfrne.2008.11.002

Cited by 769Stress Responses and CortisolHormonal and reproductive studiesAdrenal Hormones and Disorders

Neurobiological and neuropsychiatric effects of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS)

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Maninger, Nicole, Wolkowitz, Owen M., Reus, Victor I., Epel, Elissa S., Mellon, Synthia H.·2009·Frontiers in Neuroendocrinology

DOI 10.1016/j.yfrne.2008.11.002PMC PMC2725024

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Abstract

DHEA and DHEAS are steroids synthesized in human adrenals, but their function is unclear. In addition to adrenal synthesis, evidence also indicates that DHEA and DHEAS are synthesized in the brain, further suggesting a role of these hormones in brain function and development. Despite intensifying research into the biology of DHEA and DHEAS, many questions concerning their mechanisms of action and their potential involvement in neuropsychiatric illnesses remain unanswered. We review and distill the preclinical and clinical data on DHEA and DHEAS, focusing on (i) biological actions and putative mechanisms of action, (ii) differences in endogenous circulating concentrations in normal subjects and patients with neuropsychiatric diseases, and (iii) the therapeutic potential of DHEA in treating these conditions. Biological actions of DHEA and DHEAS include neuroprotection, neurite growth, and antagonistic effects on oxidants and glucocorticoids. Accumulating data suggest abnormal DHEA and/or DHEAS concentrations in several neuropsychiatric conditions. The evidence that DHEA and DHEAS may be fruitful targets for pharmacotherapy in some conditions is reviewed.

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Animal models show that DHEA lessens cortisol's harmful effects on the central nervous system.
“animal models have shown that DHEA reduces the adverse effects of cortisol on the central nervous system (81)”
From The Impact of Stress and Major Depressive Disorder on Hippocampal and Medial Prefrontal Cortex Morphology (2019) · cites this paper as [81]
Lower levels of DHEA have been described late in the course of chronic illness.
“Interestingly, one previous study has shown high serum levels of dehydroepiandrosterone-sulphate (DHEA-S), a hormone with anti-glucocorticoid action, in patients with first-episode psychosis (Strous et al., 2004), while lower levels of DHEA have been described late in the course of chronic illness (Maninger et al., 2009).”
From Abnormal cortisol levels during the day and cortisol awakening response in first-episode psychosis: The role of stress and of antipsychotic treatment (2010) · cites this paper as Maninger et al., 2009
The DHEA-to-cortisol ratio is more informative than either DHEA or cortisol absolute concentrations.
“The DHEA-to-cortisol ratio has been described as more informative than either DHEA or cortisol absolute concentrations in particular regarding the possible effect of these hormones on cognitive function (Maninger et al., 2009).”
From Abnormal cortisol levels during the day and cortisol awakening response in first-episode psychosis: The role of stress and of antipsychotic treatment (2010) · cites this paper as Maninger et al., 2009
DHEA has anabolic and antiglucocorticoid effects, as opposed to cortisol, a catabolic hormone.
“As opposed to cortisol, a catabolic hormone, DHEA has anabolic and antiglucocorticoid effects (Kalimi et al., 1994; Maninger et al., 2009).”
From Effect of oxytocin on craving and stress response in marijuana-dependent individuals: A pilot study (2013) · cites this paper as Maninger et al., 2009

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Research works printed but not linked: 2

[336]Wolkowitz OM Reus VI Manfredi F Roberts E Antiglucocorticoid effects of DHEA-S in Alzheimer’s Disease (Reply) Am J Psychiatry 1992 149 1126 1344027
[338]Wolkowitz OM Reus VI Maninger N Mellon SH Dehydroepiandrosterone in the Treatment of Neuropsychiatric Conditions Philadelphia, PA Lippincott Williams & Wilkins in press

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BackgroundInfluential
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Authors: Maninger, N., Wolkowitz, O. M., Reus, V. I., Epel, E. S., & Mellon, S. H.
Affiliations: University of California, San Francisco (US)
Corresponding author: Mellon, Synthia H.
ORCID: Wolkowitz, Owen M.
Reus, Victor I.
Epel, Elissa S.
Mellon, Synthia H.
Venue: Frontiers in Neuroendocrinology
Publisher: Elsevier BV
Published: 2009-01
Volume: 30
Issue: 1
Pages: 65-91
ISSN: 0091-3022 (ISSN-L)
DOI: 10.1016/j.yfrne.2008.11.002
PMC: PMC2725024
OpenAlex: W2042430625
Cited by: 769
References: 368
Citations by year: 2026: 38 · 2025: 45 · 2024: 36 · 2023: 45 · 2022: 39 · 2021: 47 · 2020: 70 · 2019: 41 · 2018: 59 · 2017: 45 · 2016: 51 · 2015: 34 · 2014: 47 · 2013: 47 · 2012: 49
FWCI: 1.73
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Frontiers in Neuroendocrinology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of Mental Health (T32 MH09391)
National Institute of Neurological Disorders and Stroke (NS 049462, U01NS049462)
Topics: Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Keywords: dehydroepiandrosterone, DHEA sulfate, neuropsychiatric disorders, neuroprotection, neurite outgrowth, glucocorticoid antagonism, oxidative stress, adrenal steroids
MeSH terms: Adult, Aged, Aging, Animals, Antioxidants, Brain, Dehydroepiandrosterone, Dementia, Depression, Female, Humans, Male, Middle Aged, Schizophrenia, Stress Disorders, Post-Traumatic, Neuroprotective Agents, Dehydroepiandrosterone Sulfate, Hypoxia-Ischemia, Brain

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Neurobiological and neuropsychiatric effects of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS)

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