Brief Report: Higher Peripheral Monocyte Activation Markers Are Associated With Smaller Frontal and Temporal Cortical Volumes in Women With HIV.

BACKGROUND: Persistent inflammation is a life-long complication of HIV infection, even in virally suppressed individuals. Elevated plasma concentrations of soluble(s) CD14 and CD163 have been established as biomarkers of chronic inflammation, conferring higher risk for cognitive, neurovascular, and structural abnormalities. METHODS: Structural magnetic resonance imaging (frontal and temporal regions) as well as plasma inflammatory biomarkers of monocyte activation (sCD14 and sCD163), general inflammation (plasma C-reactive protein, interleukin[IL]-6), and gut microbial translocation (plasma intestinal fatty acid-binding protein) were available on 38 women (25 with HIV) from the Chicago Women's Interagency HIV Study site. Partial least-squares models adjusting for relevant covariates (eg, age, education, and race) were conducted to evaluate the relationship between inflammatory biomarkers and brain volume in the overall sample and among women with HIV (WWH). RESULTS: In the total sample, higher plasma sCD14 was associated with smaller volumes in multiple frontal and temporal lobe regions. In the WWH-only sample, sCD163 was associated with smaller volumes only in one region of the left frontal lobe. C-reactive protein, IL-6, and intestinal fatty acid-binding protein were not associated with brain volumes for either group of women. CONCLUSIONS: Of the inflammatory monocyte markers evaluated, sCD14 was associated with smaller frontal and temporal cortical volume in the overall and WWH-only samples, while plasma sCD163 was only associated with smaller left caudal middle frontal gyrus in the WWH-only group. Validating these monocyte proteins as neurological biomarkers of structural brain deficits in a larger sample is critical for understanding HIV-associated neurobiological complications.

Diurnal and stress-reactive dehydroepiandrosterone levels and telomere length in youth.

The current investigation examined the association between the aging-related biomarkers dehydroepiandrosterone (DHEA) and telomere length (TL) in community-recruited African-American youth. The examination of DHEA included stress reactive, basal and diurnal sampling, in order to elucidate the underlying physiological process that may overlap with TL. One hundred and two participants completed the Trier Social Stressor Test for children (TSST-C). TL was obtained from all youth from buccal swabs on the same day as the TSST-C. Saliva samples from 83 participants were obtained over the course of two additional days to measure waking and diurnal levels of DHEA. DHEA diurnal slope was a robust predictor of TL (B=0.516, P<0.05), while other DHEA values were not significantly associated with TL. This study is one of the first studies to examine basal, diurnal and reactivity measurements of DHEA in youth. Furthermore, this is the first study, to our knowledge, to demonstrate a positive association between DHEA, a putative anti-aging hormone, and TL, an indicator of cellular aging.

Elevated stress is associated with prefrontal cortex dysfunction during a verbal memory task in women with HIV.

HIV-infected women may be particularly vulnerable to verbal learning and memory deficits. One factor contributing to these deficits is high perceived stress, which is associated with prefrontal cortical (PFC) atrophy and memory outcomes sensitive to PFC function, including retrieval and semantic clustering. We examined the association between stress and PFC activation during a verbal memory task in 36 HIV-infected women from the Chicago Consortium of the Women's Interagency HIV Study (WIHS) to better understand the role of the PFC in this stress-related impairment. Participants completed standardized measures of verbal learning and memory and stress (perceived stress scale-10). We used functional magnetic resonance imaging to assess brain function while participants completed encoding and recognition phases of a verbal memory task. HIV-infected women with higher stress (scores in top tertile) performed worse on all verbal memory outcomes including strategic encoding (p < 0.05) compared to HIV-infected women with lower stress (scores in lower two tertiles). Patterns of brain activation during recognition (but not encoding) differed between women with higher vs. lower stress. During recognition, women with higher stress demonstrated greater deactivation in medial PFC and posterior cingulate cortex compared to women with lower stress (p < 0.05). Greater deactivation in medial PFC marginally related to less efficient strategic retrieval (p = 0.06). Similar results were found in analyses focusing on PTSD symptoms. Results suggest that stress might alter the function of the medial PFC in HIV-infected women resulting in less efficient strategic retrieval and deficits in verbal memory.

Prefrontal cortical volume loss is associated with stress-related deficits in verbal learning and memory in HIV-infected women.

Deficits in verbal learning and memory are a prominent feature of neurocognitive function in HIV-infected women, and are associated with high levels of perceived stress. To understand the neurobiological factors contributing to this stress-related memory impairment, we examined the association between stress, verbal memory, and brain volumes in HIV-infected women. Participants included 38 HIV-infected women (Mean age=43.9years) from the Chicago Consortium of the Women's Interagency HIV Study (WIHS). Participants underwent structural magnetic resonance imaging (MRI) and completed standardized measures of verbal learning and memory and stress (Perceived Stress Scale-10; PSS-10). Brain volumes were evaluated in a priori regions of interest, including the medial temporal lobe (MTL) and prefrontal cortex (PFC). Compared to HIV-infected women with lower stress (PSS-10 scores in lower two tertiles), HIV-infected women with higher stress (scores in the top tertile), performed worse on measures of verbal learning and memory and showed smaller volumes bilaterally in the parahippocampal gyrus, superior frontal gyrus, middle frontal gyrus, and inferior frontal gyrus (p's<0.05). Reduced volumes in the inferior frontal gyrus, middle frontal gyrus, and superior frontal gyrus (all right hemisphere) were negatively associated with verbal learning and memory performance. Prefrontal cortical atrophy is associated with stress-related deficits in verbal learning and memory in HIV-infected women. The time course of these volume losses in relation to memory deficits has yet to be elucidated, but the magnitude of the volumetric differences between women with higher versus lower stress suggests a prolonged vulnerability due to chronic stress and/or early life trauma.

Experience, cortisol reactivity, and the coordination of emotional responses to skydiving.

Physiological habituation to laboratory stressors has previously been demonstrated, although the literature remains equivocal. Previous studies have found skydiving to be a salient naturalistic stressor that elicits a robust subjective and physiological stress response. However, it is uncertain whether (or how) stress reactivity habituates to this stressor given that skydiving remains a risky, life-threatening challenge with every jump despite experience. While multiple components of the stress response have been documented, it is unclear whether an individual's subjective emotions are related to their physiological responses. Documenting coordinated responsivity would lend insight into shared underlying mechanisms for the nature of habituation of both subjective (emotion) and objective (cortisol) stress responses. Therefore, we examined subjective emotion and cortisol responses in first-time compared to experienced skydivers in a predominantly male sample (total n = 44; males = 32, females = 12). Hierarchical linear modeling (HLM) revealed that experienced skydivers showed less reactivity and faster recovery compared to first-time skydivers. Subjective emotions were coordinated with physiological responses primarily within first-time skydivers. Pre-jump anxiety predicted cortisol reactivity within first-time, but not experienced, skydivers. Higher post-jump happiness predicted faster cortisol recovery after jumping although this effect overlapped somewhat with the effect of experience. Results suggest that experience may modulate the coordination of emotional response with cortisol reactivity to skydiving. Prior experience does not appear to extinguish the stress response but rather alters the individual's engagement of the HPA axis.

Genetic predictor of working memory and prefrontal function in women with HIV.

The Val158Met (rs4680) single-nucleotide polymorphism (SNP) of the catechol-O-methyltransferase gene (COMT) influences executive function and prefrontal function through its effect on dopamine (DA) metabolism. Both HIV and the Val allele of the Val158Met SNP are associated with compromised executive function and inefficient prefrontal function. The present study used behavioral and neuroimaging techniques to determine independent and interactive associations between HIV serostatus and COMT genotype on working memory and prefrontal function in women. For the behavioral study, 54 HIV-infected and 33 HIV-uninfected women completed the 0-, 1-, and 2-back conditions of the verbal N-back, a working memory test. For the imaging study, 36 women (23 HIV-infected, 13 HIV-uninfected) underwent functional magnetic resonance imaging (fMRI) assessments while completing the N-back task. HIV-infected women demonstrated significantly worse N-back performance compared with HIV-uninfected women (p < 0.05). A significant serostatus by genotype interaction (p < 0.01) revealed that, among Val/Val, but not Met allele carriers, HIV-infected women performed significantly worse than HIV-uninfected controls across N-back conditions (p < 0.01). Analogous to behavioral findings, a serostatus by genotype interaction revealed that HIV-infected Val/Val carriers showed significantly greater prefrontal activation compared with HIV-uninfected Val/Val carriers (p < 0.01). Conversely, HIV-uninfected Met allele carriers demonstrated significantly greater prefrontal activation compared with HIV-infected Met allele carriers. Findings suggest that the combination of HIV infection and the Val/Val COMT genotype leads to working memory deficits and altered prefrontal function in HIV-infected individuals.

Crack cocaine use impairs anterior cingulate and prefrontal cortex function in women with HIV infection.

Crack cocaine use is associated with impaired verbal memory in HIV-infected women more than uninfected women. To understand the neural basis for this impairment, this study examined the effects of crack cocaine use on activation of the prefrontal cortex (PFC) and strategic encoding during a verbal memory task in HIV-infected women. Three groups of HIV-infected women from the Chicago Consortium of the Women's Interagency HIV Study were compared: current users of crack cocaine (n = 10), former users of cocaine (n = 11), and women who had never used cocaine (n = 9). Participants underwent functional magnetic resonance imaging during a verbal memory task and completed a neuropsychological test of verbal memory. On the neuropsychological test, current crack users performed significantly worse than other groups on semantic clustering, a measure of strategic encoding, p < 0.05. During encoding, activation in left anterior cingulate cortex (ACC) was lower in current and former cocaine users compared to never users. During recognition, activation in bilateral PFC, specifically left dorsal medial PFC and bilateral dorsolateral PFC, was lower in current and former users compared to women who had never used cocaine. Lower activation in left dorsolateral PFC was correlated with worse performance on the recognition task, p < 0.05. The verbal learning and memory deficits associated with cocaine use in women with HIV may be partially accounted for by alterations in ACC and PFC function.

HIV and recent illicit drug use interact to affect verbal memory in women.

OBJECTIVE: HIV infection and illicit drug use are each associated with diminished cognitive performance. This study examined the separate and interactive effects of HIV and recent illicit drug use on verbal memory, processing speed, and executive function in the multicenter Women's Interagency HIV Study. METHODS: Participants included 952 HIV-infected and 443 HIV-uninfected women (mean age = 42.8, 64% African-American). Outcome measures included the Hopkins Verbal Learning Test-Revised and the Stroop test. Three drug use groups were compared: recent illicit drug users (cocaine or heroin use in past 6 months, n = 140), former users (lifetime cocaine or heroin use but not in past 6 months, n = 651), and nonusers (no lifetime use of cocaine or heroin, n = 604). RESULTS: The typical pattern of recent drug use was daily or weekly smoking of crack cocaine. HIV infection and recent illicit drug use were each associated with worse verbal learning and memory (P < 0.05). Importantly, there was an interaction between HIV serostatus and recent illicit drug use such that recent illicit drug use (compared with nonuse) negatively impacted verbal learning and memory only in HIV-infected women (P < 0.01). There was no interaction between HIV serostatus and illicit drug use on processing speed or executive function on the Stroop test. CONCLUSIONS: The interaction between HIV serostatus and recent illicit drug use on verbal learning and memory suggests a potential synergistic neurotoxicity that may affect the neural circuitry underlying performance on these tasks.

Neuropsychological characteristics and personality traits in pathological gambling.

INTRODUCTION: Pathological gambling disorder (PG) has been associated with fronto-temporal dysfunction and maladaptive personality traits, such as impulsivity and novelty seeking. The purpose of this study was to examine the predictive variance of neuropsychological and personality characteristics in PG. METHODS: Persons with PG (n=25) and a comparison group (n=34) were administered a battery of neuropsychological tests, the Temperament and Character Inventory, and the Barratt Impulsiveness Scale. Subjects with PG had evidence of fronto-temporal dysfunction as assessed by the Stroop, Wisconsin Card Sorting Test-64, Wechsler Adult Intelligence Scale Letter-Number Sequencing, Controlled Oral Word Association Test, and Boston Diagnostic Aphasia Examination Animal Naming Test. RESULTS: Subjects with PG also had impaired decision making on the Iowa Gambling Task. PG subjects had elevated levels of impulsivity, novelty seeking, and harm avoidance, and lower levels of self-directedness and cooperativeness. Logistic regression analyses indicated that neuropsychological variables did not add significant incremental variance over personality traits in predicting PG (Block chi-square=5.19, P=.074), while personality variables added significant incremental variance over neuropsychological traits in predicting PG (Block chi-square=25.13, P<.001). CONCLUSION: These results suggest that personality traits are better predictors than neuropsychological characteristics of whether someone has PG.