Fibroblast growth factors 1 and 2 in cerebrospinal fluid are associated with HIV disease, methamphetamine use, and neurocognitive functioning
Authors Bharti A, Woods S, Ellis R, Cherner M, Rosario D, Potter M, Heaton RK, Everall I, Masliah E, Grant I, Letendre S
Received 29 July 2015
Accepted for publication 9 December 2015
Published 29 April 2016 Volume 2016:8 Pages 93—99
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Venkata Atluri
Peer reviewer comments 5
Editor who approved publication: Professor Bassel Sawaya
Ajay R Bharti,1 Steven Paul Woods,2 Ronald J Ellis,3 Mariana Cherner,2 Debra Rosario,3 Michael Potter,3 Robert K Heaton,2 Ian P Everall,4 Eliezer Masliah,5 Igor Grant,2 Scott L Letendre1
On behalf of the Translational Methamphetamine AIDS Research Center Group
1Department of Medicine, 2Department of Psychiatry, 3Department of Neurosciences, University of California San Diego, San Diego, CA, USA; 4Department of Psychiatry, University of Melbourne, Victoria, Australia; 5Department of Pathology, University of Californa San Diego, San Diego, CA, USA
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 R2=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 R2=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.
Conclusion: 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.
Keywords: biomarker, cerebrospinal fluid, fibroblast growth factor, HIV, methamphetamine, HIV-associated neurocognitive disorders, HAND, neurocognitive impairment
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