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To assess whether the serotonergic and dopaminergic systems are affected, we used [<jats:sup>11<\/jats:sup>C]DASB positron emission tomography (PET) to assess presynaptic serotonergic function and [<jats:sup>18<\/jats:sup>F]FDOPA PET to measure presynaptic dopaminergic reserve in neurocognitively and psychiatrically asymptomatic PWH on ART, compared to seronegative controls (SCs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We compared [<jats:sup>11<\/jats:sup>C]DASB binding (<jats:italic>BP<\/jats:italic><jats:sub><jats:italic>ND<\/jats:italic><\/jats:sub>) (<jats:italic>n<\/jats:italic>\u2009=\u200917 PWH\/19 SCs) and [<jats:sup>18<\/jats:sup>F]FDOPA influx constant (<jats:italic>K<\/jats:italic><jats:sub><jats:italic>i<\/jats:italic><\/jats:sub>) (<jats:italic>n<\/jats:italic>\u2009=\u200920 PWH\/19 SCs) of PWH and SCs. We assessed correlations of <jats:italic>K<\/jats:italic><jats:sub><jats:italic>i<\/jats:italic><\/jats:sub> and <jats:italic>BP<\/jats:italic><jats:sub><jats:italic>ND<\/jats:italic><\/jats:sub> with CSF cytokines and imaging\/clinical\/neuropsychological outcomes using multivariable and univariable models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>BP<\/jats:italic><jats:sub><jats:italic>ND<\/jats:italic><\/jats:sub>, <jats:italic>K<\/jats:italic><jats:sub><jats:italic>i<\/jats:italic><\/jats:sub>, and neurocognitive and psychiatric scores did not differ between PWH and SCs. Higher <jats:italic>BP<\/jats:italic><jats:sub><jats:italic>ND<\/jats:italic><\/jats:sub> correlated with better neurocognitive scores in the whole group. <jats:italic>K<\/jats:italic><jats:sub><jats:italic>i<\/jats:italic><\/jats:sub> did not correlate with neurocognitive scores. Neither <jats:italic>BP<\/jats:italic><jats:sub><jats:italic>ND<\/jats:italic><\/jats:sub> nor <jats:italic>K<\/jats:italic><jats:sub><jats:italic>i<\/jats:italic><\/jats:sub> correlated with depression scores. Caudate and putamen MRI volumes trended smaller in PWH. While CSF inflammatory cytokines were higher in PWH, they did not correlate with either PET measure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretations<\/jats:title><jats:p>Presynaptic serotonin transporter density (measured by [<jats:sup>11<\/jats:sup>C]DASB) is a good correlate of the neurocognitive function in PWH and SCs. Despite long\u2010term ART, PWH still showed trends for basal ganglia volume loss, consistent with known disproportionate global and regional volume loss in PWH compared to SCs. Aspects of serotonergic and dopaminergic function, namely, presynaptic SERT density and dopaminergic reserve, however, are not different in this PWH cohort on ART from SCs, despite persistent neuroinflammation and trends of volume loss. This could reflect a functional compensatory process versus minimal, below\u2010detection\u2010level dysfunction.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.70074","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T01:38:50Z","timestamp":1747877930000},"page":"1418-1430","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Serotonergic and Dopaminergic Function in Neuropsychiatrically Asymptomatic People With <scp>HIV<\/scp> on Antiretroviral Therapy"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4337-8885","authenticated-orcid":false,"given":"Chuen\u2010Yen","family":"Lau","sequence":"first","affiliation":[{"name":"National Cancer Institute National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Lyndaker","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, Clinical Center (CC) National Institutes of Health (NIH)  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swati","family":"Shah","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, Clinical Center (CC) National Institutes of Health (NIH)  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Wakim","sequence":"additional","affiliation":[{"name":"Biostatistics and Clinical Epidemiology Service Clinical Center, NIH  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelia","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, Clinical Center (CC) National Institutes of Health (NIH)  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Monroe","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, Clinical Center (CC) National Institutes of Health (NIH)  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Kim","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, Clinical Center (CC) National Institutes of Health (NIH)  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy L.","family":"Cropper","sequence":"additional","affiliation":[{"name":"Radiology and Imaging Sciences, Clinical Center (CC) National Institutes of Health (NIH)  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3725-615X","authenticated-orcid":false,"given":"Govind","family":"Nair","sequence":"additional","affiliation":[{"name":"Translational Neuroradiology Section (D.S.R., G.N.) 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