title: Human immunodeficiency virus infection in the CNS and decreased dopamine availability: relationship with neuropsychological performance.
abstract: Human immunodeficiency virus (HIV-1) infection in the central nervous system (CNS) is associated with a wide range of neurological, cognitive, and behavioral problems. HIV-1 enters the brain soon after the initial infection and is distributed in varying concentrations in different regions with specific affinity to the subcortical regions, particularly the basal ganglia, causing neurodegeneration of dopaminergic regions and resulting in the decreased availability of dopamine (DA) in the CNS. Although there are numerous reports on HIV-1-associated neuropsychological (NP) impairment, there is a paucity of studies showing a direct relationship between the decreased availability of dopamine in different regions of postmortem brains of HIV-1-infected individuals and the level of performance in different NP functions during life. Dopamine is the key neurotransmitter in the brain and plays a regulatory role for motor and limbic functions. The purpose of the present study was to investigate the relationship between the decreased availability of dopamine found in the postmortem brain regions (fronto-cortical regions, basal ganglia, caudate, putamen, globus pallidus, and substantia nigra) of individuals with HIV/AIDS and the antemortem level of performance (assessed as T scores) in different NP functions. The relationship between HIV-1 RNA levels in different brain regions and the level of performance in different NP domains was also investigated. We found that although DA concentrations were 2-53% lower in the brain regions of HIV-1-infected, HAART-treated individuals, compared with HIV-negative controls, a 45% decrease in DA levels in the substantia nigra (SN) of HIV-1-infected individuals was significantly correlated with the low level of performance (T scores) in the speed of information processing, learning, memory, verbal fluency, and average T scores across domains. In case of homovanillic acid (HVA), the variable changes in different regions, including the substantia nigra, basal ganglia, caudate, and putamen (compared to that in the HIV-negative individuals), were significantly correlated with the level of performance (T scores) in motor functions, speed of information processing, and attention/working memory. HIVRNA levels in the frontal cortex, caudate, and GP were significantly inversely correlated with abstract/executive function, motor, learning, verbal fluency, and attention/working memory. No significant correlations were found between HIVRNA in other brain regions and NP performance. These findings suggest that the decreased availability of dopamine in the SN (the main site of DA synthesis in the CNS), and changes in the levels of HVA in different brain regions are, in part, related with the lower level of performance in some of the NP functions in individuals with HIV/AIDS.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, (D-21), P.O. Box 016960, Miami, FL 33101, USA. akumar@med.miami.edu
authors.forename: Adarsh M
authors.initials: AM
authors.lastname: Kumar
authors.forename: Raymond L
authors.initials: RL
authors.lastname: Ownby
authors.forename: Drenna
authors.initials: D
authors.lastname: Waldrop-Valverde
authors.forename: Benny
authors.initials: B
authors.lastname: Fernandez
authors.forename: Mahendra
authors.initials: M
authors.lastname: Kumar
mesh_terms: D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active; D001921:Brain / Q000378:metabolism / Q000503:physiopathology* / Q000821:virology; D003072:Cognition Disorders / Q000209:etiology / Q000503:physiopathology* / Q000821:virology; D004298:Dopamine / Q000172:deficiency*; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D015497:HIV-1; D006719:Homovanillic Acid / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D012367:RNA, Viral / Q000032:analysis
chemical_list: D012367:RNA, Viral; D004298:Dopamine; D006719:Homovanillic Acid