High early life stress and aberrant amygdala activity: risk factors for elevated neuropsychiatric symptoms in HIV+ adults

Clark, Uraina S.; Sweet, Lawrence H.; Morgello, Susan; Philip, Noah S.; Cohen, Ronald A.

doi:10.1007/s11682-016-9542-5

Cited by 17 publications

(23 citation statements)

References 159 publications

(213 reference statements)

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“…This finding supports prior data indicating that high ELS exposure is associated with cognitive dysfunction in HIV+ adults ( Clark et al, 2012 ; Spies et al, 2012 ). Considering that high ELS exposure in HIV+ adults is also 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 (depression, current stress, PTSD). While the High-ELS group did indeed demonstrate elevated neuropsychiatric symptom levels, group differences in RT-IIV persisted even after controlling for neuropsychiatric symptom levels.…”

Section: Discussionmentioning

confidence: 99%

“…Early life stress exposure was quantified using the Early Life Stress Questionnaire (ELSQ) ( Cohen et al, 2006b ), which assessed the occurrence of 17 adverse childhood events (ACE) (e.g., physical abuse, sexual abuse, neglect, family conflict, bullying) prior to age 18 years. Low ELS was defined by endorsement of fewer than 3 ACEs, and high ELS was defined as an endorsement of 3 or more ACEs, consistent with prior studies ( Cohen et al, 2006a ; Paul et al, 2008 ; Seckfort et al, 2008 ; Clark et al, 2012 , 2017 ). Using these criteria, 18 participants were classified as having low ELS and 26 were classified as having high ELS.…”

Section: Methodsmentioning

confidence: 97%

“…We examined levels of neuropsychiatric symptoms known to be elevated in HIV+ High-ELS individuals ( Clark et al, 2012 , 2017 ) and associated with RT-IIV performance ( Kaiser et al, 2008 ; Ode et al, 2011 ; Swick et al, 2012 ). Levels of current depression, stress, and PTSD symptoms were quantified using the Center for Epidemiological Studies-Depression Scale (CESD) ( Radloff, 1977 ), Perceived Stress Scale (PSS) ( Cohen et al, 1983 ), and Posttraumatic Checklist – Civilian (PCLC) ( Weathers et al, 1993 ), respectively.…”

Section: Methodsmentioning

confidence: 99%

“…Accordingly, this behavioral measure is well suited to the current investigation, as the primary aim of this study is to examine whether ELS-related cognitive reductions observed in HIV+ High-ELS adults are more strongly associated with global brain volumes than with neuropsychiatric symptoms. Building on prior findings ( Clark et al, 2012 , 2017 ; Spies et al, 2012 , 2016 ), we hypothesized that HIV+ adults with high ELS, relative to those with low ELS, would demonstrate elevations in RT-IIV, greater neuropsychiatric symptom levels, and lower total gray and white matter volumes. We further hypothesized that elevations in RT-IIV would be more strongly associated with brain volume than with neuropsychiatric symptom levels.…”

Section: Introductionmentioning

confidence: 92%

“…One unresolved question is the degree to which cognitive difficulties in HIV+ High-ELS 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 particularly concerning, given recent findings indicating that high ELS exposure is associated with elevated neuropsychiatric symptoms in HIV+ adults ( Clark et al, 2017 ).…”

Section: Introductionmentioning

confidence: 97%

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Early Life Stress-Related Elevations in Reaction Time Variability Are Associated with Brain Volume Reductions in HIV+ Adults

Clark

Rentería

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et al. 2018

Front. Behav. Neurosci.

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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.

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