HIV-associated deficits in action (verb) generation may reflect astrocytosis

Abstract

Commensurate with the hypothesized neural dissociation between verb and noun generation, research in HIV infection shows that, relative to noun fluency, action (verb) fluency is disproportionately impaired, more strongly related to executive dysfunction, and more sensitive to declines in everyday functioning. However, whether the neurobiological correlates of HIV-associated deficits in verb and noun generation are separable have not heretofore been investigated. The present study examined the biomarker correlates of action and noun fluency in 74 participants with HIV infection. Biomarkers of viral burden, neuroaxonal damage, macrophage activation, neuroprotection, inflammation, and astrocytosis were measured in plasma and cerebrospinal fluid (CSF). Deficits in action, but not noun generation, were significantly associated with higher CSF levels of S100β, a marker of astrocyte activation, even after controlling for antiretroviral therapy, current immune compromise, and general cognitive impairment. Concurrent validity for the frontal systems hypothesis of verb generation was provided by post hoc analyses demonstrating that S100β was also associated with measures of executive functions, but not semantic memory or psychomotor speed. Overall, these findings suggest that HIV-associated impairment in action fluency, and executive dysfunction more generally, may reflect astrocytosis (i.e., elevated S100β). Complementing the literature in HIV and other clinical populations with frontal systems involvement, these data also support the possible neurobiological dissociation of noun and verb generation.

Keywords:

• Human immunodeficiency virus
• Cognitive processes
• Verbal fluency
• Verbs
• Frontal lobe

This research was supported by Grants MH073419 and MH62512 from the National Institute of Mental Health. The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of Defense, or the United States Government. Aspects of these data were presented at the 36th Annual Meeting of the International Neuropsychological Society in Waikoloa, Hawaii, USA. The authors thank Janis Durelle for her assistance with biomarker assays and Lisa Moran and Catherine L. Carey for their substantial contributions to the parent grant.