Associations of cytokines, sleep patterns, and neurocognitive function in youth with HIV infection

Abstract

Youth infected with HIV at birth often have sleep disturbances, neurocognitive deficits, and abnormal psychosocial function which are associated with and possibly resulted from elevated blood cytokine levels that may lead to a decreased quality of life. To identify molecular pathways that might be associated with these disorders, we evaluated 38 HIV-infected and 35 uninfected subjects over 18-months for intracellular cytokine levels, sleep patterns and duration of sleep, and neurodevelopmental abilities. HIV infection was significantly associated with alterations of intracellular pro-inflammatory cytokines (TNF-α, IFN-γ, IL-12), sleep factors (total time asleep and daytime sleep patterns), and neurocognitive factors (parent and patient reported problems with socio-emotional, behavioral, and executive functions; working memory-mental fatigue; verbal memory; and sustained concentration and vigilance. By better defining the relationships between HIV infection, sleep disturbances, and poor psychosocial behavior and neurocognition, it may be possible to provide targeted pharmacologic and procedural interventions to improve these debilitating conditions.

Copyright © 2012 Elsevier Inc. All rights reserved.

Figures

Figure 1

Multivariate path analysis showing the significance of associations between HIV infection and cytokine, sleep, and neurodevelopment factors in HIV-infected youth using all data across all time points (0, 6, 12, and 18-months). Factor associations are indicated by directional arrows that describe the induced changes per unit with the level of significance indicated by P-values in parentheses. For example, HIV infection is associated with a 1) 8.8% decrease in ICF 2 (CD4+ and CD8+ TNF-α), 2) a 20.2 minute increase in AF 4 (total 24 hour sleep and day time sleep), and 3) a 12-point decrease in NDF 2 performance (working memory-mental fatigue). Numbers in parentheses in boxes are the averaged mean values of HIV-infected and control patients. P-values in this Figure have no direct relationship to those in Tables 3-5, but rather to Table 6 and the tables in the Appendix. *Neurodevelopmental test scores normalized to 100. (See Results: Multivariate Path Analysis Section).

Figure 2

Proposed overall associations between HIV infection, immune responses, sleep disorders, and neurocognition. Assumption of the flow of causation is indicated by the thick (HIV-dependent) arrows. HIV-dependent, immune response-independent and HIV-independent events that influence factors downstream are indicated by the thin arrows at the top of the figure.