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Nocturnal gamma-hydroxybutyrate reduces cortisol awakening response and morning kyrunenine pathway metabolites in healthy volunteers


Dornbierer, Dario A; Boxler, M; Voegel, C D; Stucky, Benjamin; Steuer, A E; Binz, T M; Baumgartner, M R; Baur, Diego M; Quednow, B B; Kraemer, T; Seifritz, E; Landolt, Hans-Peter; Bosch, O G (2019). Nocturnal gamma-hydroxybutyrate reduces cortisol awakening response and morning kyrunenine pathway metabolites in healthy volunteers. International Journal of Neuropsychopharmacology, 22(10):631-639.

Abstract

Background Gamma-hydroxybutyrate (GHB; or sodium oxybate) is an endogenous GHB-/GABAB receptor agonist. It is approved for the application in narcolepsy and has been proposed for potential treatment of Alzheimer’s and Parkinson’s disease, fibromyalgia, and depression, all of which involve neuro-immunological processes. Tryptophan catabolites (TRYCATs), the cortisol awakening response (CAR), and brain derived neurotrophic factor (BDNF) have been suggested as peripheral biomarkers of neuropsychiatric disorders. GHB has been shown to induce a delayed reduction of T helper and natural killer cell counts and alter basal cortisol levels, but GHB’s effects on TRYCATs, CAR and BDNF are unknown.
Methods Therefore, TRYCAT and BDNF serum levels as well as CAR and the affective state (Positive and Negative Affect Schedule, PANAS) were measured in the morning after a single nocturnal dose of GHB (50 mg/kg body weight) in 20 healthy male volunteers in a placebo-controlled, balanced, randomized, double-blind, cross-over design.
Results In the morning after nocturnal GHB administration, the TRYCATs indolelactic acid, kynurenine, kynurenic acid, 3-hydroxykynurenine, and quinolinic acid, the 3-hydroxykynurenine to kynurenic acid ratio and the CAR were significantly reduced (p<0.05-0.001, Benjamini-Hochberg corrected). The quinolinic acid to kynurenic acid ratio was reduced by trend. Serotonin, tryptophan, and BDNF levels as well as PANAS scores in the morning remained unchanged after nocturnal GHB challenge.
Conclusions GHB has postacute effects on peripheral biomarkers of neuropsychiatric disorders, which might be a model to explain some of its therapeutic effects in disorders involving neuro-immunological pathologies (ClinicalTrials.gov: NCT02342366).

Abstract

Background Gamma-hydroxybutyrate (GHB; or sodium oxybate) is an endogenous GHB-/GABAB receptor agonist. It is approved for the application in narcolepsy and has been proposed for potential treatment of Alzheimer’s and Parkinson’s disease, fibromyalgia, and depression, all of which involve neuro-immunological processes. Tryptophan catabolites (TRYCATs), the cortisol awakening response (CAR), and brain derived neurotrophic factor (BDNF) have been suggested as peripheral biomarkers of neuropsychiatric disorders. GHB has been shown to induce a delayed reduction of T helper and natural killer cell counts and alter basal cortisol levels, but GHB’s effects on TRYCATs, CAR and BDNF are unknown.
Methods Therefore, TRYCAT and BDNF serum levels as well as CAR and the affective state (Positive and Negative Affect Schedule, PANAS) were measured in the morning after a single nocturnal dose of GHB (50 mg/kg body weight) in 20 healthy male volunteers in a placebo-controlled, balanced, randomized, double-blind, cross-over design.
Results In the morning after nocturnal GHB administration, the TRYCATs indolelactic acid, kynurenine, kynurenic acid, 3-hydroxykynurenine, and quinolinic acid, the 3-hydroxykynurenine to kynurenic acid ratio and the CAR were significantly reduced (p<0.05-0.001, Benjamini-Hochberg corrected). The quinolinic acid to kynurenic acid ratio was reduced by trend. Serotonin, tryptophan, and BDNF levels as well as PANAS scores in the morning remained unchanged after nocturnal GHB challenge.
Conclusions GHB has postacute effects on peripheral biomarkers of neuropsychiatric disorders, which might be a model to explain some of its therapeutic effects in disorders involving neuro-immunological pathologies (ClinicalTrials.gov: NCT02342366).

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Pharmacology and Toxicology
07 Faculty of Science > Institute of Pharmacology and Toxicology

04 Faculty of Medicine > Psychiatric University Hospital Zurich > Clinic for Psychiatry, Psychotherapy, and Psychosomatics
04 Faculty of Medicine > Neuroscience Center Zurich
04 Faculty of Medicine > Institute of Legal Medicine
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Life Sciences > Pharmacology
Health Sciences > Psychiatry and Mental Health
Health Sciences > Pharmacology (medical)
Language:English
Date:1 October 2019
Deposited On:17 Sep 2019 13:36
Last Modified:11 May 2020 19:04
Publisher:Cambridge University Press
ISSN:1461-1457
Additional Information:Copyright: Cambridge University Press
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/ijnp/pyz047
Official URL:https://academic.oup.com/ijnp/advance-article/doi/10.1093/ijnp/pyz047/5559465
PubMed ID:31504554

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