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| Publication Abstract Display | | Type: Published Manuscript | | Title: Cerebrospinal fluid norepinephrine and neurocognition in HIV and methamphetamine dependence. | | Authors: Saloner R, Cherner M, Iudicello JE, Heaton RK, Letendre SL, Ellis RJ | | Year: 2020 | | Publication: Journal of Acquired Immune Deficiency Syndromes (1999) | | Volume: 85 Issue: 2 Pages: e12-e22 | | Abstract:Objective: HIV disease and methamphetamine (METH) dependence share overlapping mechanisms of neurotoxicity that preferentially compromise monoamine-rich frontostriatal circuitry. However, norepinephrine (NE) function is poorly understood in HIV and METH dependence. We evaluated associations between cerebrospinal fluid (CSF) NE and HIV, METH dependence, and neurocognition.
Methods: Participants included 125 adults, stratified by HIV serostatus (HIV+/HIV-) and recent METH dependence (METH+/METH-), who underwent comprehensive neurocognitive testing and lumbar puncture. CSF NE was assayed using high-performance liquid chromatography. Multivariable regression modelled NE as a function of HIV, METH, and their interaction, adjusting for demographic and clinical factors. Pearson's correlations examined relationships between NE and demographically-adjusted neurocognitive domain scores.
Results: HIV significantly interacted with METH (p<.001) such that compared to HIV-/METH-, CSF NE was markedly elevated in the single risk-groups (HIV+/METH- : d=0.96; HIV-/METH+: d=0.79) and modestly elevated in the dual-risk group (HIV+/METH+: d=0.48). This interaction remained significant after adjustment for lifetime depression, antidepressant use, and race/ethnicity. In the full sample, higher NE levels significantly correlated with worse global function (r=-0.19), learning (r=-0.23), and delayed recall (r=-0.18). Similar relationships between higher NE and worse neurocognition were detected in the METH- groups (i.e., HIV-/METH- and HIV+/METH-) and in the virally-suppressed persons HIV+ subgroup, but not in the METH+ groups (i.e., HIV-/METH+, HIV+/METH+).
Discussion: HIV and METH independently, but not additively, relate to noradrenergic excess in the CNS, and perturbations to noradrenergic function may represent a pathophysiological mechanism of HIV-related neurocognitive dysfunction. Consistent with prior reports that noradrenergic excess compromises hippocampal and prefrontal function, higher NE related to worse neurocognition, even among successfully-treated PWH. Pharmacological and psychosocial interventions that stabilize NE function may improve neurocognition in PWH. |
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