Roger C. McIntosh

Self-reported sleep disturbance is associated with lower CD4 count and 24-h urinary dopamine levels in ethnic minority women living with HIV

BACKGROUND Sleep disturbance is associated with dopamine dysregulation, which can negatively impact immune status. Individuals living with HIV experience more sleep difficulties, and poor sleep may compound immune decrements associated with HIV infection. Little research has examined associations between sleep, dopamine, and immune status (CD4 count) in individuals with HIV. As ethnic minority women living with HIV (WLWH) are at heightened risk for HIV disease progression, we related sleep reports to both CD4 count and dopamine levels in a cohort of ethnic minority WLWH. METHODS Participants were 139 low-income WLWH (ages 20-62; 78.3% African-American or Caribbean) who reported both overall sleep quality and sleep disturbance on the Pittsburgh sleep quality index (PSQI). CD4 count and HIV viral load were measured via morning peripheral venous blood samples, and concentrations of dopamine were measured via 24-h urine collection. Covariates included HIV viral load, length of time since HIV diagnosis, HAART adherence, perceived stress and depression. RESULTS After controlling for all covariates, greater sleep disturbance was associated with significantly lower CD4 count (β=-.20, p=.03) and lower levels of dopamine (β=-.25, p=.04). Poorer overall sleep quality was marginally associated with lower CD4 count (β=-.16, p=.08), and was not associated with dopamine. CONCLUSION Our analyses suggest that sleep disturbance is independently related with immune status and dopamine levels in WLWH. Lower levels of dopamine may indicate neuroendocrine dysregulation and may impact immune and health status. Results highlight sleep disturbance rather than overall sleep quality as potentially salient to neuroendocrine and immune status in ethnic minority WLWH.

Neuropathological sequelae of Human Immunodeficiency Virus and apathy: A review of neuropsychological and neuroimaging studies

Apathy remains a common neuropsychiatric disturbance in the Human Immunodeficiency Virus (HIV-1) despite advances in anti-retroviral treatment (ART). The goal of the current review is to recapitulate findings relating apathy to the deleterious biobehavioral effects of HIV-1 in the post-ART era. Available literatures demonstrate that the emergence of apathy with other neurocognitive and neuropsychiatric symptoms may be attributed to neurotoxic effects of viral proliferation, e.g., aggregative effect of Tat and gp120 on apoptosis, transport and other enzymatic reactions amongst dopaminergic neurons and neuroglia. An assortment of neuroimaging modalities converge on the severity of apathy symptoms associated with the propensity of the virus to replicate within frontal-striatal brain circuits that facilitate emotional processing. Burgeoning research into functional brain connectivity also supports the effects of microvascular and neuro-inflammatory injury linked to aging with HIV-1 on the presentation of neuropsychiatric symptoms. Summarizing these findings, we review domains of HIV-associated neurocognitive and neuropsychiatric impairment linked to apathy in HIV. Taken together, these lines of research suggest that loss of affective, cognitive and behavioral inertia is commensurate with the neuropathology of HIV-1.

Emotionally negative pictures increase attention to a subsequent auditory stimulus.

Emotionally negative stimuli serve as a mechanism of biological preparedness to enhance attention. We hypothesized that emotionally negative stimuli would also serve as motivational priming to increase attention resources for subsequent stimuli. To that end, we tested 11 participants in a dual sensory modality task, wherein emotionally negative pictures were contrasted with emotionally neutral pictures and each picture was followed 600 ms later by a tone in an auditory oddball paradigm. Each trial began with a picture displayed for 200 ms; half of the trials began with an emotionally negative picture and half of the trials began with an emotionally neutral picture; 600 ms following picture presentation, the participants heard either an oddball tone or a standard tone. At the end of each trial (picture followed by tone), the participants categorized, with a button press, the picture and tone combination. As expected, and consistent with previous studies, we found an enhanced visual late positive potential (latency range=300-700 ms) to the negative picture stimuli. We further found that compared to neutral pictures, negative pictures resulted in early attention and orienting effects to subsequent tones (measured through an enhanced N1 and N2) and sustained attention effects only to the subsequent oddball tones (measured through late processing negativity, latency range=400-700 ms). Number pad responses to both the picture and tone category showed the shortest response latencies and greatest percentage of correct picture-tone categorization on the negative picture followed by oddball tone trials. Consistent with previous work on natural selective attention, our results support the idea that emotional stimuli can alter attention resource allocation. This finding has broad implications for human attention and performance as it specifically shows the conditions in which an emotionally negative stimulus can result in extended stimulus evaluation.

Alexithymia is linked to neurocognitive, psychological, neuroendocrine, and immune dysfunction in persons living with HIV.

The neuropathological changes resulting from Human Immunodeficiency Virus (HIV) infection may manifest in alexithymia (AL), a multidimensional trait characterized by impairments in the cognitive assimilation of feelings and emotions. A sample of 93 HIV survivors scoring high, i.e., ⩾74 on the 26-item Toronto Alexithymia Scale (TAS-26), were compared to 79 low AL (TAS-26⩽54) survivors on measures of neurocognitive, psychological, neuroendocrine and immune function. Neurocognitive function was evinced by a standardized test of psychomotor speed, cognitive flexibility and task switching ability, HIV Dementia and general cognitive status. Patients were also screened for levels of depression, anxiety and psychological stress. A 24-h urinary norepinephrine (NE) and cortisol (CORT) collection was taken; blood was drawn for T lymphocyte subset counts (CD4+CD3+) and HIV-1 viral load. Alexithymic patients exhibited higher levels of executive dysfunction, psychological distress, norepinephrine-to-cortisol (NE/CORT) ratio and viral load. Linear regression models accounting for sociodemographic and disease-related variables revealed two AL subscales, difficulties identifying and describing feelings, predicted and explained a significant proportion of variance in the outcome measures. Specifically, poorer executive task-switching/cognitive flexibility was associated with greater difficulty describing feelings; dysregulated autonomic response (high NE/CORT ratio) and depressive symptoms were predicted by difficulty identifying feelings; higher levels of anxiety and psychological stress were both predicted by greater difficulty describing and identifying feelings. Overall, the psychoneuroimmunological profile of alexithymia in HIV positive persons at mid-stage of infection suggests a greater vulnerability for disease progression.

Cognitive vulnerability for depression in HIV

UNLABELLED Biased inhibitory processing, frequency and valence of automatic thoughts, and inability to use positive schemas to regulate negative mood are cognitive factors linked to depression. These processes may underlie the established link between adaptive cognitive coping strategies (acceptance and positive reframing) and depression in persons with HIV. How individual differences in HIV-related neurocognitive deficits moderate such effects is unknown. In a secondary analysis, we tested the direct effects of coping on depressed affect as mediated by the frequency and valence of automatic thoughts and how this model was moderated by neurocognitive function in a cohort of HIV+ men and women. METHODS HIV+ adults (mage=39.8, SD=9.5) provided data for the baseline assessment of a randomized trial that investigated the effects of a cognitive-behavioral stress management intervention. Measures included coping, depressive symptoms, positive (PAT) and negative automatic thoughts (NAT), and HIV-dementia. RESULTS After controlling for covariates, cognitive coping was related to depressed mood as mediated via NAT (β=-.92) and PATs (β=.61), (R(2)=.42, F(7, 325)=33.50, p<.0001). The indirect effect of coping on depressive symptoms via NAT and PAT was moderated by neurocognitive function. LIMITATION Cross-sectional design does not allow for the inference of causation among the variables. CONCLUSION Results support a cognitive vulnerability model for depression whereby HIV-related neurocognitive deficits interfere with the ability to use acceptance and positive reframing strategies to increase the frequency of PAT and decrease NAT in adults living with symptoms of depression.

HIV-positive females show blunted neurophysiological responses in an emotion–attention dual task paradigm

OBJECTIVE Although HIV is associated with decreased emotional and cognitive functioning, the mechanisms through which affective changes can alter cognitive processes in HIV-infected individuals are unknown. We aimed to clarify this question through testing the extent to which emotionally negative stimuli prime attention to a subsequent infrequently occurring auditory tone in HIV+ compared to HIV- females. METHODS Attention to emotional compared to non-emotional pictures was measured via the LPP ERP. Subsequent attention was indexed through the N1 and late processing negativity ERP. We also assessed mood and cognitive functioning in both groups. RESULTS In HIV- females, emotionally negative pictures, compared to neutral pictures, resulted in an enhanced LPP to the pictures and an enhanced N1 to subsequent tones. The HIV+ group did not show a difference in the LPP measure between picture categories, and accordingly, did not show a priming effect to the subsequent infrequent tones. CONCLUSIONS The ERP findings, combined with neuropsychological deficits, suggest that HIV+ females show impairments in attention to emotionally-laden stimuli and that this impairment might be related to a loss of affective priming. SIGNIFICANCE This study is the first to provide physiological evidence that the LPP, a measure of attention to emotionally-charged visual stimuli, is reduced in HIV-infected individuals. These results set the stage for future work aimed at localizing brain activation to emotional stimuli in HIV+ individuals.

Reduced functional connectivity between ventromedial prefrontal cortex and insula relates to longer corrected QT interval in HIV+ and HIV− individuals

OBJECTIVE Prolongation of the QT interval, i.e., measure of the time between the start of the Q wave and the end of the T wave, is a precursor to fatal cardiac arrhythmias commonly observed in individuals infected with the Human Immunodeficiency Virus (HIV), and is related to dysregulation of the autonomic nervous system. We investigated the relationship between QT interval length and resting state functional connectivity (rsFC) of the ventromedial prefrontal cortex (VMPFC), a core region of the brain that is involved with cardio-autonomic regulation. METHOD Eighteen HIV+ men on antiretroviral therapy and with no history of heart disease were compared with 26 HIV-negative control subjects who had similar demographic and cardio-metabolic characteristics. A seed-based rsFC analysis of the right and left VMPFC was performed at the individual subject level, and 2nd-level analyses were conducted to identify the following: group differences in connectivity, brain regions correlating with corrected (QTc) interval length before and after controlling for those group differences, and regions where seed-based rsFC correlates with CD4 count and QTc interval within HIV+ individuals. RESULTS HIV-negative adults showed greater rsFC between the VMPFC seed regions and several default mode network structures. Across groups greater rsFC with the left anterior insula was associated with shorter QTc intervals, whereas right posterior insula connectivity with the VMPFC correlated with greater QTc intervals. HIV patients with lower CD4 counts and higher QTc intervals showed greater rsFC between the right VMPFC and the right posterior insula and dorsal cingulate gyrus. CONCLUSIONS This study demonstrates that QTc interval lengths are associated with distinct patterns of VMPFC rsFC with posterior and anterior insula. In HIV patients, longer QTc interval and lower CD4 count corresponded to weaker VMPFC connectivity with the dorsal striatrum. SIGNIFICANCE A forebrain control mechanism may be implicated in the suppression of cardiovagal influence that confers risk for ventricular arrhythmias and sudden cardiac death in HIV+ individuals.

Interhemispheric Asymmetries and Theta Activity in the Rostral Anterior Cingulate Cortex as EEG Signature of HIV-Related Depression: Gender Matters.

Resting EEGs of 40 people living with HIV (PLWH) on long-term antiretroviral treatment were examined for z-scored deviations from a healthy control (normative database) to examine the main and interaction effects of depression and gender. Regions of interest were frontal (alpha) and central (all bands) for interhemispheric asymmetries in quantitative EEGs and theta in the rostral anterior cingulate cortex (rACC) in low-resolution electromagnetic tomography (LORETA). Z-scored normed deviations of depressed PLWH, compared with nondepressed, showed right-dominant interhemispheric asymmetries in all regions. However, after adjusting for multiple testing, significance remained only central for theta, alpha, and beta. Reversed (left-dominant) frontal alpha asymmetry is a potential EEG marker of depression in the HIV negative population that was not reversed in depressive PLWH; however, corresponding with extant literature, gender had an effect on the size of frontal alpha asymmetry. The LORETA analysis revealed a trending interactional effect of depression and gender on theta activity in the rACC in Brodmann area 32. We found that compared to men, women had greater right-dominant frontal alpha-asymmetry and elevated theta activity in voxels of the rACC, which may indicate less likelihood of depression and a higher likelihood of response to antidepressants. In conclusion, subtle EEG deviations, such as right-dominant central theta, alpha, and beta asymmetries and theta activity in the rACC may mark HIV-related depressive symptoms and may predict the likelihood of response to antidepressants but gender effects need to be taken into account. Although this study introduced the use of LORETA to examine the neurophysiological correlates of negative affect in PLWH, further research is needed to assess the utility of this tool in diagnostics and treatment monitoring of depression in PLWH.

Doctor-Patient Relationship: Active Patient Involvement (DPR:API) is related to long survival status and predicts adherence change in HIV

Background: Active patient involvement is one of the aims of patient-centered care. Little is known regarding the unique impact of patients’ active participation in their care on health outcomes, and scales are needed to measure this construct. The aim of the present study was to examine the application of the Doctor-Patient Relationship: Active Patient Involvement (DPR:API) scale, a 5-item scale, in predicting relevant health outcomes among HIV positive patients. Methods: In Study 1 we compared active patient involvement between long survivors (those who survived more than twice as long as expected after getting an AIDS defining symptom; n=176) and normal course controls (HIV positive patients; n=79). Study 2 was a longitudinal study following the normal course controls to determine whether active patient involvement at baseline would predict adherence to combination antiretroviral therapy (ART; percentage of missed doses) using the AIDS Clinical Trials Group scale (ACTG) at one-year follow-up. Results: In Study 1, long survivors were significantly higher on active patient involvement than the normal course HIV controls. In Study 2, hierarchical multiple regression models showed that patients’ involvement in their care at baseline significantly predicted change in percentage of missed doses one year later, such that patients who were more involved early in treatment became more adherent to ART after one year. Conclusion: Findings highlight the relevance of patient involvement in their care to important health outcomes. Interventions designed to help patients become more active in their care throughout the illness trajectory might positively affect medication-taking behaviors and survival. The DRP:API offers an easy and quickly-administered tool to assess patient involvement within the context of both research and practice.

Current assessment of heart rate variability and QTc interval length in HIV/AIDS

Purpose of review The increasing prevalence of cardiovascular disease comorbidity in persons infected with the HIV has become a global concern. The electrocardiogram (ECG) is increasingly being utilized to provide clinically relevant information regarding cardiac arrhythmias and cardio-autonomic dysfunction. The purpose of this review is to summarize the latest research comparing QT and R-to-R interval length as a function of HIV+ status or antiretroviral therapy (ART) regimen. Recent findings Prolongation of the corrected QTc interval may be acquired in HIV+ ART-naive individuals, exacerbated by various classes of ART drugs, and is generally predictive of lethal cardiac arrhythmias, with effects observed from childhood to adulthood. Recent literature also suggests the trend of lower heart rate variability in HIV is indicative of cardiorespiratory and inflammatory-immune dysfunction. Summary These emergent studies support the clinical relevance of the ECG across the age and HIV disease spectrum. Furthermore, the reported findings have implications for the management of cardiovascular and chronic inflammatory disease comorbidity in persons living with HIV.