Low Neuroactive Steroids Identifies a Biological Subtype of Depression in Adults with Human Immunodeficiency Virus on Suppressive Antiretroviral Therapy
Year: 2020
Type: article
Study design: Observational Study
Abstract: 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.
Language: English
Subfield: Behavioral Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,763
Funders: U.S. Department of Veterans Affairs, Harvard University, Harvard University Center for AIDS Research, National Institutes of Health, Center for AIDS Research, University of Washington, University of California, San Diego, Veterans Affairs San Diego Healthcare System, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Institute on Drug Abuse, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, Fogarty International Center, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Institute of Child Health and Human Development, National Institute on Minority Health and Health Disparities, Eunice Kennedy Shriver National Institute of Child Health and Human Development, HIV Neurobehavioral Research Center, University of California, San Diego
Awards: G1205301529, G130322559, G1353012146, G1575283533, G1858258047, G1910588693, G255310873, California NeuroAIDS Tissue Network, G345173699, G3471390838, G3550442147, G3586383482, G4559771646, G4913483794, G5641659859, Texas NeuroAIDS Research Center, G6739876316, Midcareer Investigator Award in Patient-Oriented NeuroAIDS Research, G8534000477, G9000013331, G9000014056, G9000054876, G9000073635, G9000198349, HIV Neurobehavioral Research Center, G90079629
OpenAlex ID: W3011920098