DHEA metabolism to the neurosteroid androsterone: a possible mechanism of DHEA’s antidepressant action

Dor, Rivka Ben; Marx, Christine E.; Shampine, Lawrence J.; Rubinow, David R.; Schmidt, Peter J.

doi:10.1007/s00213-015-3991-1

Cited by 15 publications

(6 citation statements)

References 52 publications

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“…However, as previously suggested (e.g., Rasmusson et al, 2006b), a balance between the inhibitory effects of allo + pregnan and the excitatory effects of DHEA(S) in the central nervous system may influence PTSD symptoms severity; i.e., DHEA(S) may confer stress resilience only when balanced by adequate synthesis of allo + pregnan. However, it is also possible that a lower ratio of allo + pregnan to DHEA(S) in CSF reflects reduced conversion of DHEA to other stress protective compounds: a) androsterone (Dor et al, 2015), another potent GABAergic neurosteroid produced by the serial activity of 5α-reductase and 3α-HSD (Fig. 1), and b) 5-androsten-3β, 17β-diol (ADIOL) (Saijo et al,2011).…”

Section: Evidence For the Impact Of Allo + Pregnan On Ptsd Severity Imentioning

confidence: 99%

Relationships between cerebrospinal fluid GABAergic neurosteroid levels and symptom severity in men with PTSD

Rasmusson

King

Valovski

et al. 2019

Psychoneuroendocrinology

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Allopregnanolone and pregnanolone (together termed allo + pregnan) are neurosteroid metabolites of proges-terone that equipotently facilitate the action of gamma-amino-butyric acid (GABA) at GABA A receptors. The adrenal steroid dehydroepiandrosterone (DHEA) allosterically antagonizes GABA A receptors and facilitates N-methyl-D-aspartate (NMDA) receptor function. In prior research, premenopausal women with posttraumatic stress disorder (PTSD) displayed low cerebrospinal fluid (CSF) levels of allo + pregnan [undifferentiated by the gas chromatographymass spectrometry (GC-MS) method used] that correlated strongly and negatively with PTSD reexperiencing and negative mood symptoms. A PTSD-related decrease in the ratio of allo + pregnan to 5α-dihydroprogesterone (5α-DHP: immediate precursor for Allopregnanolone) suggested a block in synthesis of these neurosteroids at 3α-hydroxysteroid dehydrogenase (3α-HSD). In the current study, CSF was collected from unmedicated, tobacco-free men with PTSD (n = 13) and trauma-exposed healthy controls (n = 17) after an overnight fast. Individual CSF steroids were quantified separately by GC-MS. In the men with PTSD, allo + pregnan correlated negatively with Clinician-Administered PTSD Scale (CAPS-IV) total (ρ = −0.74, p = 0.006)and CAPS-IV derived Simms dysphoria cluster (ρ = −0.71, p = 0.01) scores. The allo + pregnan to DHEA ratio

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Section: Evidence For the Impact Of Allo + Pregnan On Ptsd Severity Imentioning

confidence: 99%

Relationships between cerebrospinal fluid GABAergic neurosteroid levels and symptom severity in men with PTSD

Rasmusson

King

Valovski

et al. 2019

Psychoneuroendocrinology

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“…More specifically in relation to the effect of DHEA on mood, several possibilities have been discussed in an attempt to explain DHEA's mechanism of physiological action. One possibility would be an indirect DHEA action on mood with testosterone and estradiol, hormones that can influence mood and of which DHEA is a precursor (Ben Dor, Marx, Shampine, Rubinow, & Schmidt, 2015). Another possibility would be its action on cortisol.…”

Section: Introductionmentioning

confidence: 99%

Dehydroepiandrosterone for depressive symptoms: A systematic review and meta‐analysis of randomized controlled trials

Peixoto

Grande

Carrilho

et al. 2020

J of Neuroscience Research

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Depression is a mental disorder that affects millions of people around the world. However, depressive symptoms can be seen in other psychiatric and medical conditions. Here, we investigate the effect of DHEA treatment on depressive symptoms in individuals with depression and/or other clinical conditions in which depressive symptoms are present. An electronic search was performed until October 2019, with no restrictions on language or year of publication in the following databases: Medline, EMBASE, LILACS, and Cochrane Library. Randomized controlled trials comparing DHEA versus placebo were included if the depressive symptoms were assessed. Fifteen studies with 853 female and male individuals were included in this review. To conduct the meta-analysis, data were extracted from 14 studies. In comparison with placebo, DHEA improved depressive symptoms (standardized mean difference [SMD] −0.28, 95% (CI) −0.45 to −0.11, p =.001, 12 studies, 742 individuals (375 in the experimental group and 367 in the placebo group), I 2 = 24%), very low quality of evidence, 2 of 14 studies reporting this outcome were removed in a sensitivity analysis as they were strongly influencing heterogeneity between studies. No hormonal changes that indicated any risk to the participants' health were seen. Side effects observed were uncommon, mild, and transient, but commonly related to androgyny. In conclusion, DHEA was associated with a beneficial effect on depressive symptoms compared to placebo. However, these results should be viewed with caution, since the quality of evidence for this outcome was considered very low according to the GRADE criteria.

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“…Several studies in humans and animals have demonstrated that neurosteroids could have psychotropic actions. In particular, studies in humans demonstrate that DHEA could have a potential role in the mitigation of stress and could have positive effects on mood symptoms in depressive disorders as antidepressant and on human well-being (Bloch, Ish-Shalom, Greenman, Klein, & Latzer, 2012;Dor, Marx, Shampine, Rubinow, & Schmidt, 2015;Russo, Murrough, Han, Charney, & Nestler, 2012;Maninger, Wolkowitz, Reus, Epel, & Mellon, 2009). On the contrary, researches demonstrate that high-prolonged cortisol concentration, detectable by hair analysis, can damage the organism (Stalder & Kirshbaum, 2012).…”

Section: Discussionmentioning

confidence: 99%

Natural Horse Boarding Vs Traditional Stable: A Comparison of Hormonal, Hematological and Immunological Parameters

Placci

Marliani

Sabioni³

et al. 2019

Journal of Applied Animal Welfare Science

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DHEA metabolism to the neurosteroid androsterone: a possible mechanism of DHEA’s antidepressant action

Abstract: The small sample size notwithstanding, these data emphasize the potential behavioral relevance of ADT in humans, which may include contribution to the antidepressant effects of DHEA.

Cited by 15 publications

References 52 publications

Relationships between cerebrospinal fluid GABAergic neurosteroid levels and symptom severity in men with PTSD

Relationships between cerebrospinal fluid GABAergic neurosteroid levels and symptom severity in men with PTSD

Dehydroepiandrosterone for depressive symptoms: A systematic review and meta‐analysis of randomized controlled trials

Natural Horse Boarding Vs Traditional Stable: A Comparison of Hormonal, Hematological and Immunological Parameters

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