Joseph M Gullett1,2, Damon G Lamb1,2,3,4, Eric Porges1,2, Adam J Woods1,2, Jake Rieke3, Paul Thompson5, Neda Jahanshad5, Talia M Nir5, Karen Tashima6, Ronald A Cohen1,2. 1. Center for Cognitive Aging and Memory , McKnight Brain Institute, University of Florida, Gainesville, Florida. 2. Department of Clinical and Health Psychology , University of Florida, Gainesville, Florida. 3. Brain Rehabilitation Research Center , Malcom Randall VA Medical Center, Gainesville, Florida. 4. Department of Neurology , University of Florida, Gainesville, Florida. 5. Imaging Genetics Center , Mark and Mary Stevens Neuroimaging and Informatics Institute, USC Keck School of Medicine, Marina del Rey, California. 6. The Miriam Hospital , Alpert College of Medicine, Brown University, Providence, Rhode Island.
Abstract
BACKGROUND: Alcohol use disorder (AUD) is prevalent among individuals diagnosed with human immunodeficiency virus (HIV), and both HIV and alcohol use have been shown to negatively affect the integrity of white matter pathways in the brain. Behavioral, functional, and anatomical impairments have been linked independently to HIV and alcohol use, and these impairments have bases in specific frontally mediated pathways within the brain. METHODS: Magnetic resonance imaging data were acquired for 37 HIV+ participants without dementia or hepatitis C. Imaging data were processed through the FreeSurfer and TraCULA pipelines to obtain 4 bilateral frontal white matter tracts for each participant. Diffusion metrics of white matter integrity along the highest probability pathway for each tract were analyzed with respect to demographics, disease-specific variables, and reported substance use. RESULTS: Significantly increased axial diffusivity (decreased axonal integrity) and a trending increase in mean diffusivity were observed along the anterior thalamic radiation (ATR) in participants with a history of AUD. A diagnosis of AUD explained over 36% of the variance in diffusivity along the ATR overall when accounting for clinical variables including nadir CD4 and age-adjusted HIV infection length. CONCLUSIONS: This study provides evidence of HIV-related associations between alcohol use and indicators of axonal integrity loss along the ATR, a frontal pathway involved in the inhibition of addictive or unwanted behaviors. Reduced axonal integrity of this pathway was greatest in HIV+ participants with an AUD, even when considering the effect of age-adjusted disease length and severity (nadir CD4). This finding implicates a potential biological mechanism linking reduced integrity of frontal white matter to the high prevalence of AUD in an HIV+ population without dementia or hepatitis C.
BACKGROUND:Alcohol use disorder (AUD) is prevalent among individuals diagnosed with human immunodeficiency virus (HIV), and both HIV and alcohol use have been shown to negatively affect the integrity of white matter pathways in the brain. Behavioral, functional, and anatomical impairments have been linked independently to HIV and alcohol use, and these impairments have bases in specific frontally mediated pathways within the brain. METHODS: Magnetic resonance imaging data were acquired for 37 HIV+ participants without dementia or hepatitis C. Imaging data were processed through the FreeSurfer and TraCULA pipelines to obtain 4 bilateral frontal white matter tracts for each participant. Diffusion metrics of white matter integrity along the highest probability pathway for each tract were analyzed with respect to demographics, disease-specific variables, and reported substance use. RESULTS: Significantly increased axial diffusivity (decreased axonal integrity) and a trending increase in mean diffusivity were observed along the anterior thalamic radiation (ATR) in participants with a history of AUD. A diagnosis of AUD explained over 36% of the variance in diffusivity along the ATR overall when accounting for clinical variables including nadir CD4 and age-adjusted HIV infection length. CONCLUSIONS: This study provides evidence of HIV-related associations between alcohol use and indicators of axonal integrity loss along the ATR, a frontal pathway involved in the inhibition of addictive or unwanted behaviors. Reduced axonal integrity of this pathway was greatest in HIV+ participants with an AUD, even when considering the effect of age-adjusted disease length and severity (nadir CD4). This finding implicates a potential biological mechanism linking reduced integrity of frontal white matter to the high prevalence of AUD in an HIV+ population without dementia or hepatitis C.
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