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HIV-Associated Apathy/Depression and Neurocognitive Impairments Reflect Persistent Dopamine Deficits.

ABSTRACT: Individuals living with human immunodeficiency virus type 1 (HIV-1) are often plagued by debilitating neurocognitive impairments and affective alterations;the pathophysiology underlying these deficits likely includes dopaminergic system dysfunction. The present review utilized four interrelated aims to critically examine the evidence for dopaminergic alterations following HIV-1 viral protein exposure. First, basal dopamine (DA) values are dependent upon both brain region andexperimental approach (i.e., high-performance liquid chromatography, microdialysis or fast-scan cyclic voltammetry). Second, neurochemical measurements overwhelmingly support decreased DA concentrations following chronic HIV-1 viral protein exposure. Neurocognitive impairments, including alterations in pre-attentive processes and attention, as well as apathetic behaviors, provide an additional line of evidence for dopaminergic deficits in HIV-1. Third, to date, there is no compelling evidence that combination antiretroviral therapy (cART), the primary treatment regimen for HIV-1 seropositive individuals, has any direct pharmacological action on the dopaminergic system. Fourth, the infection of microglia by HIV-1 viral proteins may mechanistically underlie the dopamine deficit observed following chronic HIV-1 viral protein exposure. An inclusive and critical evaluation of the literature, therefore, supports the fundamental conclusion that long-term HIV-1 viral protein exposure leads to a decreased dopaminergic state, which continues to persist despite the advent of cART. Thus, effective treatment of HIV-1-associated apathy/depression and neurocognitive impairments must focus on strategies for rectifying decreases in dopamine function.

SUBMITTER: McLaurin KA

PROVIDER: S-EPMC8392364 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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HIV-Associated Apathy/Depression and Neurocognitive Impairments Reflect Persistent Dopamine Deficits.

McLaurin Kristen A KA Harris Michael M Madormo Victor V Harrod Steven B SB Mactutus Charles F CF Booze Rosemarie M RM

Cells 20210821 8

Individuals living with human immunodeficiency virus type 1 (HIV-1) are often plagued by debilitating neurocognitive impairments and affective alterations;the pathophysiology underlying these deficits likely includes dopaminergic system dysfunction. The present review utilized four interrelated aims to critically examine the evidence for dopaminergic alterations following HIV-1 viral protein exposure. First, basal dopamine (DA) values are dependent upon both brain region andexperimental approach ...[more]

PMID: 34440928

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Project description:BackgroundHIV/AIDS-associated neurocognitive impairments negatively affect treatment adherence, viral load suppression, CD4 count, functionality, and the overall quality of life of people with seropositive status. However, huge variability is observed across primary studies regarding the prevalence and determinants of neurocognitive impairment in people with HIV/AIDS. This systematic review and meta-analysis sought to determine the pooled prevalence of neurocognitive impairment and identify factors contributing to variations in its estimate among people living with HIV/AIDS in Africa.MethodsA comprehensive literature search of scientific databases (Medline/PubMed, SCOPUS, Web of Science, PsycINFO, and EMBASE) was performed from inception onward. Google and Google Scholar were also searched for grey literature. Research articles available until July 15, 2022 were included. We used STATA-version 14 statistical software for analysis. A random effect model was executed to pool the reported prevalence of neurocognitive impairments. Subgroup analysis was done to show variations in the prevalence of neurocognitive impairments and factors that might contribute to these variations.ResultsA literature search resulted in 8,047 articles. After the removal of duplications and thorough evaluation, a total of 49 studies were included in the meta-analysis. The prevalence of HIV/AIDS-associated neurocognitive impairments was highly variable across studies, ranging from 14% to 88%, yielding the pooled prevalence of HIV/AIDS-associated neurocognitive impairment to be 46.34% [95% CI (40.32, 52.36)] and I2 = 98.5% with a P-value of 0.001.ConclusionsA large proportion of people living with HIV/AIDS in Africa have HIV/AIDS-associated neurocognitive impairment. This illustrates the need to establish practical approaches to early identification and effective control of HIV/AIDS-associated neurocognitive impairments. However, there were variabilities in the reported prevalence of HIV/AIDS-associated neurocognitive impairments across studies. This further demonstrates the need to have consistent measurement approaches.Trial registrationPROSPERO 2022, "CRD42020166572".

Project description:Human immunodeficiency virus (HIV) continues to have adverse effects on cognition and the brain in many infected people, despite a reduced incidence of HIV-associated dementia with combined antiretroviral therapy (cART). Working memory is often affected, along with attention, executive control, and cognitive processing speed. Verbal working memory (VWM) requires the interaction of each of the cognitive component processes along with a phonological loop for verbal repetition and rehearsal. HIV-related functional brain response abnormalities during VWM are evident in functional MRI (fMRI), though the neural substrate underlying these neurocognitive deficits is not well understood. The current study addressed this by comparing 24 HIV+ to 27 demographically matched HIV-seronegative (HIV-) adults with respect to fMRI activation on a VWM paradigm (n-back) relative to performance on two standardized tests of executive control, attention and processing speed (Stroop and Trail Making A-B). As expected, the HIV+ group had deficits on these neurocognitive tests compared to HIV- controls, and also differed in neural response on fMRI relative to neuropsychological performance. Reduced activation in VWM task-related brain regions on the 2-back was associated with Stroop interference deficits in HIV+ but not with either Trail Making A or B performance. Activation of the posterior cingulate cortex (PCC) of the default mode network during rest was associated with Hopkins Verbal Learning Test-2 (HVLT-2) learning in HIV+. These effects were not observed in the HIV- controls. Reduced dynamic range of neural response was also evident in HIV+ adults when activation on the 2-back condition was compared to the extent of activation of the default mode network during periods of rest. Neural dynamic range was associated with both Stroop and HVLT-2 performance. These findings provide evidence that HIV-associated alterations in neural activation induced by VWM demands and during rest differentially predict executive-attention and verbal learning deficits. That the Stroop, but not Trail Making was associated with VWM activation suggests that attentional regulation difficulties in suppressing interference and/or conflict regulation are a component of working memory deficits in HIV+ adults. Alterations in neural dynamic range may be a useful index of the impact of HIV on functional brain response and as a fMRI metric in predicting cognitive outcomes.

Dataset Information

HIV-Associated Apathy/Depression and Neurocognitive Impairments Reflect Persistent Dopamine Deficits.

Publications

HIV-Associated Apathy/Depression and Neurocognitive Impairments Reflect Persistent Dopamine Deficits.

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