Low Neuroactive Steroids Identifies a Biological Subtype of Depression in Adults with Human Immunodeficiency Virus on Suppressive Antiretroviral Therapy.
depression
DHEA
HIV
HPA axis
acylcarnitines
metabolomics
neuroactive steroids
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
20 05 2021
20 05 2021
Historique:
received:
23
09
2019
accepted:
03
03
2020
pubmed:
12
3
2020
medline:
12
2
2022
entrez:
12
3
2020
Statut:
ppublish
Résumé
The prevalence and mortality risk of depression in people with human immunodeficiency virus (HIV) infection receiving antiretroviral therapy (ART) is higher than in the general population, yet biomarkers for therapeutic targeting are unknown. In the current study, we aimed to identify plasma metabolites associated with depressive symptoms in people with HIV receiving ART. This is a prospective study of ART-treated HIV-infected adults with or without depressive symptoms assessed using longitudinal Beck Depression Inventory scores. Plasma metabolite profiling was performed in 2 independent cohorts (total n = 99) using liquid and gas chromatography and tandem mass spectrometry. Participants with depressive symptoms had lower neuroactive steroids (dehydroepiandrosterone sulfate [DHEA-S], androstenediols, and pregnenolone sulfate) compared with those without depressive symptoms. The cortisol/DHEA-S ratio, an indicator of hypothalamic-pituitary-adrenal axis imbalance, was associated with depressive symptoms (P < .01) because of low DHEA-S levels, whereas cortisol was similar between groups. The odds of having depressive symptoms increased with higher cortisol/DHEA-S ratios (adjusted odds ratio, 2.5 per 1-unit increase in z score; 95% confidence interval, 1.3-4.7), independent of age and sex. The kynurenine-to-tryptophan ratio showed no significant associations. These findings suggest that altered neuroactive steroid metabolism may contribute to the pathophysiological mechanisms of depression in ART-treated HIV-infected adults, representing a potential biological pathway for therapeutic targeting.
Sections du résumé
BACKGROUND
The prevalence and mortality risk of depression in people with human immunodeficiency virus (HIV) infection receiving antiretroviral therapy (ART) is higher than in the general population, yet biomarkers for therapeutic targeting are unknown. In the current study, we aimed to identify plasma metabolites associated with depressive symptoms in people with HIV receiving ART.
METHODS
This is a prospective study of ART-treated HIV-infected adults with or without depressive symptoms assessed using longitudinal Beck Depression Inventory scores. Plasma metabolite profiling was performed in 2 independent cohorts (total n = 99) using liquid and gas chromatography and tandem mass spectrometry.
RESULTS
Participants with depressive symptoms had lower neuroactive steroids (dehydroepiandrosterone sulfate [DHEA-S], androstenediols, and pregnenolone sulfate) compared with those without depressive symptoms. The cortisol/DHEA-S ratio, an indicator of hypothalamic-pituitary-adrenal axis imbalance, was associated with depressive symptoms (P < .01) because of low DHEA-S levels, whereas cortisol was similar between groups. The odds of having depressive symptoms increased with higher cortisol/DHEA-S ratios (adjusted odds ratio, 2.5 per 1-unit increase in z score; 95% confidence interval, 1.3-4.7), independent of age and sex. The kynurenine-to-tryptophan ratio showed no significant associations.
CONCLUSIONS
These findings suggest that altered neuroactive steroid metabolism may contribute to the pathophysiological mechanisms of depression in ART-treated HIV-infected adults, representing a potential biological pathway for therapeutic targeting.
Identifiants
pubmed: 32157292
pii: 5802682
doi: 10.1093/infdis/jiaa104
pmc: PMC8136979
doi:
Substances chimiques
Neurosteroids
0
Dehydroepiandrosterone
459AG36T1B
Hydrocortisone
WI4X0X7BPJ
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1601-1611Subventions
Organisme : NIMH NIH HHS
ID : U24 MH100929
Pays : United States
Organisme : NIMH NIH HHS
ID : U24 MH100931
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH097659
Pays : United States
Organisme : NIMH NIH HHS
ID : K23 MH115812
Pays : United States
Organisme : NIMH NIH HHS
ID : P30 MH062512
Pays : United States
Organisme : NIMH NIH HHS
ID : U24 MH100930
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI060354
Pays : United States
Organisme : NIMH NIH HHS
ID : U24 MH100925
Pays : United States
Organisme : NIMH NIH HHS
ID : K24 MH097673
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH110259
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA040391
Pays : United States
Organisme : NIMH NIH HHS
ID : U24 MH100928
Pays : United States
Informations de copyright
© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.
Références
Biochem Pharmacol. 2005 Jul 15;70(2):249-57
pubmed: 15904896
J Acquir Immune Defic Syndr. 2015 May 1;69(1):18-28
pubmed: 25942456
Cell Mol Life Sci. 2004 Feb;61(4):393-416
pubmed: 14999402
HIV Med. 2019 May;20(5):317-329
pubmed: 30924577
Front Pharmacol. 2018 Apr 11;9:354
pubmed: 29695968
Curr HIV/AIDS Rep. 2019 Feb;16(1):82-95
pubmed: 30661180
Expert Rev Mol Med. 2006 Aug 31;8(20):1-27
pubmed: 16942634
Sci Rep. 2018 Apr 27;8(1):6681
pubmed: 29703925
Brain Behav Immun. 2008 Aug;22(6):881-9
pubmed: 18261883
Clin Endocrinol (Oxf). 2001 Sep;55(3):325-30
pubmed: 11589675
Front Neuroendocrinol. 2015 Jan;36:28-48
pubmed: 24929099
Psychoneuroendocrinology. 2009 Jan;34(1):19-26
pubmed: 18805642
Am J Epidemiol. 2017 May 15;185(10):869-878
pubmed: 28430844
J Acquir Immune Defic Syndr. 2007 Apr 1;44(4):411-6
pubmed: 17195762
Science. 2017 Jul 28;357(6349):
pubmed: 28751584
Curr Opin Endocrinol Diabetes Obes. 2010 Jun;17(3):205-9
pubmed: 20404726
Curr Drug Targets. 2014;15(9):901-14
pubmed: 25039497
BMC Infect Dis. 2013 May 04;13:203
pubmed: 23641933
Life Sci. 2002 Sep 6;71(16):1837-48
pubmed: 12175700
Sci Rep. 2017 Aug 30;7(1):9967
pubmed: 28855630
Lancet. 2018 Sep 22;392(10152):1058-1070
pubmed: 30177236
Eur J Clin Invest. 2002 Oct;32(10):775-84
pubmed: 12406027
JAMA Psychiatry. 2018 Apr 1;75(4):379-385
pubmed: 29466531
Nat Rev Endocrinol. 2015 Oct;11(10):617-25
pubmed: 26303601
Psychoneuroendocrinology. 2012 Jul;37(7):929-36
pubmed: 22133517
Mol Pharmacol. 1996 Jul;50(1):67-74
pubmed: 8700121
Nat Commun. 2018 Oct 26;9(1):4490
pubmed: 30367044
Am J Psychiatry. 2006 Jan;163(1):59-66
pubmed: 16390890
Psychoneuroendocrinology. 2019 Feb;100:203-212
pubmed: 30388594
Ann Intern Med. 1999 Mar 16;130(6):461-70
pubmed: 10075613
Front Psychiatry. 2015 Jul 14;6:97
pubmed: 26236243
AIDS Behav. 2019 Dec;23(12):3452-3459
pubmed: 31367965
Psychopharmacology (Berl). 2014 Sep;231(17):3557-67
pubmed: 24846476
Arch Gen Psychiatry. 2003 Feb;60(2):133-41
pubmed: 12578430
Int J Tryptophan Res. 2016 Oct 26;9:79-88
pubmed: 27812290
Psychopharmacology (Berl). 2019 Oct;236(10):2997-3011
pubmed: 30806743
J Affect Disord. 2017 Nov;222:32-39
pubmed: 28668713
Psychoneuroendocrinology. 2015 Sep;59:91-101
pubmed: 26036454
PLoS One. 2014 Mar 24;9(3):e92842
pubmed: 24663122
Am J Psychiatry. 1999 Apr;156(4):646-9
pubmed: 10200751
PLoS One. 2015 Oct 22;10(10):e0140943
pubmed: 26492488
J Mol Endocrinol. 2016 Apr;56(3):R139-55
pubmed: 26908835
J Acquir Immune Defic Syndr. 2014 Apr 1;65(4):456-62
pubmed: 24220289
JAMA Cardiol. 2016 Nov 1;1(8):929-937
pubmed: 27557332
Clin Chim Acta. 2009 Nov;409(1-2):4-10
pubmed: 19576195
HIV Med. 2001 Apr;2(2):136-8
pubmed: 11737391
Arch Gen Psychiatry. 2005 Feb;62(2):154-62
pubmed: 15699292