Abstract
There is burgeoning evidence that, among HIV+ adults, exposure to high levels of early life stress (ELS) is associated with increased cognitive impairment as well as brain volume abnormalities and elevated neuropsychiatric symptoms. Currently, we have a limited understanding of the degree to which cognitive difficulties observed in HIV+ High-ELS samples reflect underlying neural abnormalities rather than increases in neuropsychiatric symptoms. Here, we utilized a behavioral marker of cognitive function, reaction time intra-individual variability (RT-IIV), which is sensitive to both brain volume reductions and neuropsychiatric symptoms, to elucidate the unique contributions of brain volume abnormalities and neuropsychiatric symptoms to cognitive difficulties in HIV+ High-ELS adults. We assessed the relation of RT-IIV to neuropsychiatric symptom levels and total gray and white matter volumes in 44 HIV+ adults (26 with high ELS). RT-IIV was examined during a working memory task. Self-report measures assessed current neuropsychiatric symptoms (depression, stress, post-traumatic stress disorder). Magnetic resonance imaging was used to quantify total gray and white matter volumes. Compared to Low-ELS participants, High-ELS participants exhibited elevated RT-IIV, elevated neuropsychiatric symptoms, and reduced gray and white matter volumes. Across the entire sample, RT-IIV was significantly associated with gray and white matter volumes, whereas significant associations with neuropsychiatric symptoms were not observed. In the High-ELS group, despite the presence of elevated neuropsychiatric symptom levels, brain volume reductions explained more than 13% of the variance in RT-IIV, whereas neuropsychiatric symptoms explained less than 1%. Collectively, these data provide evidence that, in HIV+ High-ELS adults, ELS-related cognitive difficulties (as indexed by RT-IIV) exhibit strong associations with global brain volumes, whereas ELS-related elevations in neuropsychiatric symptoms appear to contribute minimally to these cognitive difficulties. Such findings support a growing body of evidence indicating that high ELS exposure is a significant risk factor for neurocognitive dysfunction in HIV+ adults. Further, these data highlight the need to better understand how ELS-related pathophysiological mechanisms contribute to volumetric and other neural abnormalities in HIV+ individuals.
Highlights
Recent studies indicate that exposure to high levels of early life stress (ELS) can increase the risk of cognitive impairment among HIV+ adults (Clark et al, 2012; Spies et al, 2012; Womersley et al, 2017)
We examined the relation of reaction time intraindividual variability (RT-IIV) to neuropsychiatric symptoms and gray matter volumes using hierarchical regression (Table 2)
Considering that high ELS exposure in HIV+ adults is associated with elevated neuropsychiatric symptoms (Myers et al, 2006; Clark et al, 2017), which are known to be associated with elevations in RT-IIV (Ode et al, 2011; Swick et al, 2012), we examined whether RT-IIV elevations in the High-ELS group were driven by neuropsychiatric symptoms
Summary
Recent studies indicate that exposure to high levels of early life stress (ELS) can increase the risk of cognitive impairment among HIV+ adults (Clark et al, 2012; Spies et al, 2012; Womersley et al, 2017). One unresolved question is the degree to which cognitive difficulties in HIV+ HighELS adults reflect underlying neural abnormalities as opposed to neuropsychiatric symptoms (e.g., depression, post-traumatic stress disorder [PTSD]), which have detrimental effects on cognitive functions (Ode et al, 2011; Swick et al, 2012; Fellows et al, 2013). This is concerning, given recent findings indicating that high ELS exposure is associated with elevated neuropsychiatric symptoms in HIV+ adults (Clark et al, 2017). While the aforementioned studies utilized neuropsychological batteries that were tailored to detect HIV-related cognitive decline, the current study takes a novel approach by utilizing a sensitive behavioral measure of cognitive function, reaction time intraindividual variability (RT-IIV), to examine these issues in greater depth
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