title: Biomarkers and neurodevelopment in perinatally HIV-infected or exposed youth: a structural equation model analysis.
abstract: OBJECTIVE
  To examine the relationship between markers of vascular dysfunction and neurodevelopmental outcomes in perinatally HIV-infected (PHIV+) and perinatally HIV-exposed but uninfected (PHEU) youth.
  
  
  METHODS
  Cross-sectional design within a prospective, 15-site US-based cohort study.
  
  
  METHODS
  Neurodevelopmental outcomes were evaluated in relation to nine selected vascular biomarkers in 342 youth (212 PHIV+, 130 PHEU). Serum levels were assessed for adiponectin, C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), soluble vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sE-selectin), monocyte chemoattractant protein (sMCP-1), intercellular adhesion molecule-1 (sICAM-1), and P-selectin (sP-selectin). The Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) was administered at entry, yielding a Full-Scale IQ score, and four index scores. Factor analysis was conducted to reduce the biomarkers to fewer factors with related biological roles. Structural equation models (SEMs) were used to measure associations between resulting factors and WISC-IV scores.
  
  
  RESULTS
  Mean participant age was 11.4 years, 54% were female, 70% black. The nine biomarkers were clustered into three factor groups: F1 (fibrinogen, CRP, and IL-6); F2 (sICAM-1 and sVCAM-1); and F3 (MCP-1, sP-selectin, and sE-selectin). Adiponectin showed little correlation with any factor. SEMs revealed significant negative association of F1 with WISC-IV processing speed score in the total cohort. This effect remained significant after adjusting for HIV status and other potential confounders. A similar association was observed when restricted to PHIV+ participants in both unadjusted and adjusted SEMs.
  
  
  CONCLUSIONS
  Aggregate measures of fibrinogen, CRP, and IL-6 may serve as a latent biomarker associated with relatively decreased processing speed in both PHIV+ and PHEU youth.
authors.affiliation: aNational Institute of Mental Health, National Institutes of Health, Bethesda, Maryland bDepartment of Biostatistics, Harvard School of Public Health, Boston, Massachusetts cDepartment of Neurosciences, University of California San Diego, San Diego, California dCenter for Neural Development and Disease, University of Rochester Medical Center, Rochester, New York eUniversity of Miami Miller School of Medicine, Miami, Florida fEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland gDivision of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida hFeinberg School of Medicine, Northwestern University, Chicago, Illinois iDepartment of Psychiatry, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Suad
authors.initials: S
authors.lastname: Kapetanovic
authors.forename: Ray
authors.initials: R
authors.lastname: Griner
authors.forename: Bret
authors.initials: B
authors.lastname: Zeldow
authors.forename: Sharon
authors.initials: S
authors.lastname: Nichols
authors.forename: Erin
authors.initials: E
authors.lastname: Leister
authors.forename: Harris A
authors.initials: HA
authors.lastname: Gelbard
authors.forename: Tracie L
authors.initials: TL
authors.lastname: Miller
authors.forename: Rohan
authors.initials: R
authors.lastname: Hazra
authors.forename: Armando J
authors.initials: AJ
authors.lastname: Mendez
authors.forename: Kathleen
authors.initials: K
authors.lastname: Malee
authors.forename: Betsy
authors.initials: B
authors.lastname: Kammerer
authors.forename: Paige L
authors.initials: PL
authors.lastname: Williams
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood*; D002648:Child; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D008297:Male; D009422:Nervous System Diseases / Q000473:pathology*; D011446:Prospective Studies; D014481:United States
chemical_list: D015415:Biomarkers