title: Fibroblast growth factors 1 and 2 in cerebrospinal fluid are associated with HIV disease, methamphetamine use, and neurocognitive functioning.
abstract: BACKGROUND
  Human immunodeficiency virus (HIV) and methamphetamine use commonly affect neurocognitive (NC) functioning. We evaluated the relationships between NC functioning and two fibroblast growth factors (FGFs) in volunteers who differed in HIV serostatus and methamphetamine dependence (MAD).
  
  
  METHODS
  A total of 100 volunteers were categorized into four groups based on HIV serostatus and MAD in the prior year. FGF-1 and FGF-2 were measured in cerebrospinal fluid by enzyme-linked immunosorbent assays along with two reference biomarkers (monocyte chemotactic protein [MCP]-1 and neopterin). Comprehensive NC testing was summarized by global and domain impairment ratings.
  
  
  RESULTS
  Sixty-three volunteers were HIV+ and 59 had a history of MAD. FGF-1, FGF-2, and both reference biomarkers differed by HIV and MAD status. For example, FGF-1 levels were lower in subjects who had either HIV or MAD than in HIV- and MAD- controls (P=0.003). Multivariable regression identified that global NC impairment was associated with an interaction between FGF-1 and FGF-2 (model R(2)=0.09, P=0.01): higher FGF-2 levels were only associated with neurocognitive impairment among subjects who had lower FGF-1 levels. Including other covariates in the model (including antidepressant use) strengthened the model (model R(2)=0.18, P=0.004) but did not weaken the association with FGF-1 and FGF-2. Lower FGF-1 levels were associated with impairment in five of seven cognitive domains, more than FGF-2, MCP-1, or neopterin.
  
  
  CONCLUSIONS
  These findings provide in vivo support that HIV and MAD alter expression of FGFs, which may contribute to the NC abnormalities associated with these conditions. These cross-sectional findings cannot establish causality and the therapeutic benefits of recombinant FGF-1 need to be investigated.
authors.affiliation: Department of Medicine, University of California San Diego, San Diego, CA, USA.
authors.forename: Ajay R
authors.initials: AR
authors.lastname: Bharti
authors.affiliation: Department of Psychiatry, University of California San Diego, San Diego, CA, USA.
authors.forename: Steven Paul
authors.initials: SP
authors.lastname: Woods
authors.affiliation: Department of Neurosciences, University of California San Diego, San Diego, CA, USA.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Ellis
authors.affiliation: Department of Psychiatry, University of California San Diego, San Diego, CA, USA.
authors.forename: Mariana
authors.initials: M
authors.lastname: Cherner
authors.affiliation: Department of Neurosciences, University of California San Diego, San Diego, CA, USA.
authors.forename: Debra
authors.initials: D
authors.lastname: Rosario
authors.affiliation: Department of Neurosciences, University of California San Diego, San Diego, CA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Potter
authors.affiliation: Department of Psychiatry, University of California San Diego, San Diego, CA, USA.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Heaton
authors.affiliation: Department of Psychiatry, University of Melbourne, Victoria, Australia.
authors.forename: Ian P
authors.initials: IP
authors.lastname: Everall
authors.affiliation: Department of Pathology, University of Californa San Diego, San Diego, CA, USA.
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
authors.affiliation: Department of Psychiatry, University of California San Diego, San Diego, CA, USA.
authors.forename: Igor
authors.initials: I
authors.lastname: Grant
authors.affiliation: Department of Medicine, University of California San Diego, San Diego, CA, USA.
authors.forename: Scott L
authors.initials: SL
authors.lastname: Letendre
keywords: HAND; HIV; HIV-associated neurocognitive disorders; biomarker; cerebrospinal fluid; fibroblast growth factor; methamphetamine; neurocognitive impairment