title: Lower total and regional grey matter brain volumes in youth with perinatally-acquired HIV infection: Associations with HIV disease severity, substance use, and cognition.
abstract: Despite improved survival due to combination antiretroviral therapy (cART), youth with perinatally-acquired HIV (PHIV) show cognitive deficits and developmental delay at increased rates. HIV affects the brain during critical periods of development, and the brain may be a persistent reservoir for HIV due to suboptimal blood brain barrier penetration of cART. We conducted structural magnetic resonance imaging (sMRI) and cognitive testing in 40 PHIV youth (mean age=16.7years) recruited from the NIH Pediatric HIV/AIDS Cohort Study (PHACS) who are part of the first generation of PHIV youth surviving into adulthood. Historical and current HIV disease severity and substance use measures were also collected. Total and regional cortical grey matter brain volumes were compared to a group of 334 typically-developing, HIV-unexposed and uninfected youth (frequency-matched for age and sex) from the Pediatric Imaging, Neurocognition, and Genetics (PING) study (mean age=16.1years). PHIV youth had smaller (2.8-5.1%) total and regional grey matter volumes than HIV-unexposed and uninfected youth, with smallest volumes seen among PHIV youth with higher past peak viral load (VL) and recent unsuppressed VL. In PHIV youth, worse cognitive performance correlated with smaller volumes. This pattern of smaller grey matter volumes suggests that PHIV infection may influence brain development and underlie cognitive dysfunction seen in this population. Among PHIV youth, smaller volumes were also linked to substance use (alcohol use: 9.0-13.4%; marijuana use: 10.1-16.0%). In this study, collection of substance use information was limited to the PHIV cohort; future studies should also collect substance use information in controls to further address interactions between HIV and substance use on brain volume.
authors.affiliation: Northwestern University Interdepartmental Neuroscience Program, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.
authors.forename: C Paula
authors.initials: CP
authors.lastname: Lewis-de Los Angeles
authors.affiliation: Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, United States.
authors.forename: Paige L
authors.initials: PL
authors.lastname: Williams
authors.affiliation: Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, United States.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Huo
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.
authors.forename: Shirlene D
authors.initials: SD
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Children's Hospital Los Angeles, Los Angeles, CA, United States.
authors.forename: Kristina A
authors.initials: KA
authors.lastname: Uban
authors.affiliation: Department of Pediatrics, Children's Hospital Los Angeles, Los Angeles, CA, United States.
authors.forename: Megan M
authors.initials: MM
authors.lastname: Herting
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Malee
authors.affiliation: Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, United States.
authors.forename: Ram
authors.initials: R
authors.lastname: Yogev
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.
authors.forename: John G
authors.initials: JG
authors.lastname: Csernansky
authors.affiliation: Department of Neurosciences, University of California, San Diego, La Jolla, CA, United States.
authors.forename: Sharon
authors.initials: S
authors.lastname: Nichols
authors.affiliation: Department of Pediatrics, Tulane University School of Medicine, New Orleans, LA, United States.
authors.forename: Russell B
authors.initials: RB
authors.lastname: Van Dyke
authors.affiliation: Department of Pediatrics, Children's Hospital Los Angeles, Los Angeles, CA, United States; Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Sowell
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States; Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States. Electronic address: leiwang1@northwestern.edu.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology; D002648:Child; D003071:Cognition / Q000502:physiology*; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging* / Q000473:pathology; D015658:HIV Infections / Q000150:complications / Q000000981:diagnostic imaging* / Q000473:pathology / Q000635:transmission; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D009929:Organ Size / Q000502:physiology; D012720:Severity of Illness Index; D019966:Substance-Related Disorders / Q000150:complications / Q000000981:diagnostic imaging* / Q000473:pathology; D055815:Young Adult
keywords: Adolescence; Brain; Development; Grey matter; HIV; Magnetic resonance imaging; Neuroimaging; Neuropsychology; Perinatally-acquired