Potential Mechanism for HIV-Associated Depression

Upregulation of Serotonin Transporters in SIV-Infected Macaques Detected by 11C-Dasb PET

Bibliographic Data

ID15524691
AuthorsSwati Shah (0000-0002-7333-9086, National Institutes of Health Clinical Center), Sanhita Sinharay (0000-0001-9910-996X, National Institutes of Health Clinical Center), Kenta Matsuda (0000-0001-7746-3028, National Institute of Allergy and Infectious Diseases), William Schreiber-Stainthorp (0000-0002-7386-8754, National Institutes of Health Clinical Center), Siva Muthusamy (National Institutes of Health Clinical Center), Dianne Lee (0009-0001-7054-7904, National Institutes of Health Clinical Center), Paul Wakim (0000-0002-5951-0983, National Institutes of Health Clinical Center), Vanessa M Hirsch (0000-0002-1228-7761, National Institute of Allergy and Infectious Diseases), Vanessa Hirsch, Avindra Nath (0000-0003-0927-5855, National Institute of Neurological Disorders and Stroke), Michele Di Mascio (0000-0001-6609-9689, Office of AIDS Research), Dima A Hammoud (0000-0001-7406-7871, National Institutes of Health Clinical Center, corresponding author)
Year2019
Volume10
Pages362-362
Publication date2019-05-23
Open AccessYes
TypeARTICLE
VenueFrontiers in Psychiatry (JOURNAL)
Journal identifiersISSN: 1664-0640 • E-ISSN: 1664-0640
PublisherFrontiers Media (PUBLISHER • CH)
DOI10.3389/fpsyt.2019.00362
PMID31178771
OpenAlexW2945347233
LanguageEN
Citations received1
References cited58

Purpose: Increased incidence of depression in HIV+ patients is associated with lower adherence to treatment and increased morbidity/mortality. One possible underlying pathophysiology is serotonergic dysfunction. In this study, we used an animal model of HIV, the SIV-infected macaque, to longitudinally image serotonin transporter (SERT) expression before and after inoculation, using 11C-DASB (SERT ligand) PET imaging. Methods: We infected seven rhesus macaques with a neurovirulent SIV strain and imaged them at baseline and multiple time points after inoculation (group A). Pyrosequencing methylation analysis of the SERT promoter region was performed. We also measured SERT mRNA/protein in brain single-cell suspensions from another group (group B) of SIV-infected animals (n = 13). Results: Despite some animals showing early fluctuations, 86% of our group A animals eventually showed a net increase in midbrain/thalamus binding potential (BP ND ) over the course of their disease (mean increased binding between last time point and baseline = 30.2% and 32.2%, respectively). Repeated-measures mixed-model analysis showed infection duration to be predictive of midbrain BP ND (p = 0.039). Thalamic BP ND was statistically significantly associated with multiple CSF cytokines (P Conclusion: Upregulated SERT leading to lower synaptic levels of serotonin is a possible mechanism of depression in HIV+ patients, and extrapolating our conclusions from SIV to HIV should be sought using translational human studies

Biology · Human immunodeficiency virus (HIV · Macaque · Receptor · Serotonergic · Serotonin · Serotonin transporter · Simian immunodeficiency virus · Thalamus · Bipolar Disorder and Treatment · HIV Research and Treatment · Medicine · Neuroscience · Tryptophan and brain disorders · Endocrinology · Immunology · Internal Medicine

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