The Evolution of Assessing Central Nervous System Complications in Human Immunodeficiency Virus: Where Do We Go From Here?

In this fifth decade of the human immunodeficiency virus (HIV) epidemic, central nervous system (CNS) complications including cognitive impairment and mental health remain a burden for people with HIV (PWH) on antiretroviral therapy. Despite the persistence of these complications, which often co-occur, the underlying pathophysiology remains elusive and consequently treatments remain limited. To continue to grow our understanding of the underlying mechanisms of CNS complications among PWH, there is a need to reexamine our current approaches, which are now more than 2 decades old. At the 2021 National Institutes of Health-sponsored meeting on Biotypes of CNS Complications in PWH, the Neurobehavioral Working Group addressed the following: (1) challenges inherent to determining CNS complications; (2) heterogeneity in CNS complications; and (3) problems and solutions for examining integrated biotypes. The review below provides a summary of the main points presented and discussed by the Neurobehavioral Working Group at the meeting.

Anterior Insula Activation During Cardiac Interoception Relates to Depressive Symptom Severity in HIV-Positive and HIV-Negative Postmenopausal Women.

OBJECTIVE: This study aimed to determine whether subclinical symptoms of depression in postmenopausal women are associated with blood oxygen level-dependent (BOLD) activity within the anterior insula during cardiac interoceptive awareness and whether this association differs for persons living with the human immunodeficiency virus (PWH). METHOD: Twenty-three postmenopausal (mean [standard deviation] age = 56.5 [4.8] years) and 27 HIV-negative women (mean [standard deviation] age = 56.4 [8.0]) underwent functional magnetic resonance imaging while performing a heartbeat detection task. BOLD activation within the bilateral anterior insula based on the contrast of a heartbeat detection condition with and without a distracting tone was entered along with age, HIV status, and psychological stress into two multivariate regression models with self-reported depressive symptom severity as the outcome. RESULTS: Depressive symptoms did not vary by HIV status, nor was there a main effect or interaction for PWH on insula BOLD activation. Depressive symptoms were positively associated with psychological stress for the left ( ß = 0.310, t (49) = 2.352, p = .023) and right brain models ( ß = 0.296, t (49) = 2.265, p = .028) as well as the magnitude of BOLD activation in the left insula ( ß = 0.290, t (49) = 2.218, p = .032) and right insula ( ß = 0.318, t (49) = 2.453, p = .018), respectively. Exploratory analyses revealed that greater magnitude of BOLD activation attributed to exteroceptive noise (tone) was also correlated with self-reported distrust and preoccupation with interoceptive sensations. CONCLUSIONS: Results support an active interference model for interoceptive awareness wherein greater BOLD signal in the anterior insula in the presence of distracting exteroceptive stimuli may reflect greater prediction error, a feature of depression.

Impaired Neurocognitive Performance and Mortality in HIV: Assessing the Prognostic Value of the HIV-Dementia Scale.

This study examined whether global HIV-associated neurocognitive impairment (NCI), assessed with the HIV-Dementia Scale (HDS), predicted mortality in an ethnically diverse sample of 209 HIV-positive adults. Participants were predominantly in the mid-range of illness at baseline, and followed over 13-years. At baseline, 31 (15%) participants scored in the NCI range (HDS ≤ 10); 58 (28%) died during follow-up. Baseline NCI was significantly associated with earlier mortality (HR = 2.10, 95% CI [1.10-4.00]) independent of sociodemographic and HIV disease-related covariates. Less errors on the antisaccade task, an index of executive/attention control, was the only HDS subtest predicting earlier mortality (HR = 0.72, 95% CI [0.58-0.90]). In the absence of an AIDS-defining condition, NCI, particularly in the executive/attention domain, is an independent prognostic marker of mortality in a diverse HIV-positive cohort. These findings highlight the clinical utility of brief cognitive screening measures in this population.

Psychosocial risk and management of physical diseases.

During the 40 years since the Yale conference on Behavioral Medicine and the founding of the Journal of Behavioral Medicine considerable progress has been made in understanding the role of psychosocial risk and management of physical diseases. We here describe the development of these fundamental concepts from early research on stress through studies of the Type A behavior pattern to more contemporary approaches to the relationship between psychosocial risks and benefits in relation to disease processes. This includes the relationship of psychosocial risk to cancers, cardiovascular diseases (CVD), cardiometabolic disorders, Human Immunodeficiency Virus (HIV)/Acquired Human Immune Deficiency Syndrome. During the past 40 years the effects of prolonged distress responses in the pathogenesis of some cancers and CVD have been well-established and modifiable behavioral, cognitive and social factors have been shown to produce favorable outcome components in the management of such diseases as breast cancer, coronary heart disease and HIV.

Resting-state connectivity and spontaneous activity of ventromedial prefrontal cortex predict depressive symptomology and peripheral inflammation in HIV.

Depression and chronic inflammation are common in persons infected with the human immunodeficiency virus (HIV+). Although depression and response to inflammatory challenge are shown to reflect activity in common neural networks, little is known regarding sub-clinical presentation in persons chronically infected with HIV. The relationship of resting-state functional connectivity (rsFC) between the subgenual anterior cingulate cortex (sgACC) and bilateral amygdala to Beck Depression Inventory-1 (BDI) scores were compared within a group of 23 HIV+ and 23 HIV-negative comparison adults. An interaction was found wherein lower rsFC between the sgACC and both right and left amygdala was associated with higher BDI scores in HIV+ individuals. Total BDI scores and plasma levels of IL-6, IL-8, TNF-α, and IL-10 made available from 10 of the HIV+ patients were regressed upon an index of spontaneous whole-brain activity at rest; i.e., the amplitude of low-frequency fluctuations (ALFFs). Elevated levels of depression and IL-6 were associated with increased ALFF in a cluster of voxels on the medial portion of the ventral surface of the frontal lobe (Brodmann Area 11). Within this sample of HIV+ individuals lower rsFC of the sgACC with subcortical limbic regions predicts greater burden of depressive symptomology whereas elevated activity in the adjacent BA 11 may reflect sickness, indexed by elevated IL-6, and associated depressive behaviors.

Change in urinary cortisol excretion mediates the effect of angry/hostile mood on 9 month diastolic blood pressure in HIV+ adults.

Cardiovascular disease is a growing concern in HIV disease management and nearly 1 out of 3 persons living with the virus is hypertensive. Biobehavioral factors such as anger, hostility, and HPA axis reactivity are emperically linked to blood pressure regulation. Whether HPA axis or mood disturbance increases risk for hypertension remains unclear in HIV disease. The aim of this study was to determine whether 9-month change in angry/hostile mood predicts alterations in systolic (SBP) or diastolic blood pressure (DBP), and whether this change is mediated by 24-h urinary cortisol (CORT) output. Sixty-one HIV positive adults, aged 41.1 ± 8.6 years, assigned to the control condition of a stress management intervention provided blood samples, 24-h urine specimens, blood pressure in-office, and self-reported mood at baseline and a 9-month follow-up. CORT was tested as a mediator in two separate models controlling for baseline BP, CD4 count, HIV-1 viral load, protease inhibitor use, body mass index, smoking status, and family history of cardiometabolic disease. Increase in angry/hostile mood was associated with greater SBP (ß = 0.33, CI 0.09, 0.56, p = 0.01) and DBP (ß = 0.39, CI 0.16, 0.62, p < 0.001) at follow-up. CORT partially mediated the effect of angry/hostile mood on DBP (ß = 0.28, CI 0.03, 0.54, p = 0.03). Change in CORT was not related to SBP (ß = 0.12, CI -0.20, 0.44, p = 0.46). The final mediation model accounted for 41.2% of the variance in 9-month DBP. Angry or hostile mood may contribute to increased risk for hypertension in persons treated for HIV via disturbance of the HPA-axis.

Psychological Distress Mediates the Effect of Alexithymia on 2-Year Change in HIV Viral Load.

PURPOSE: Individuals with trait alexithymia (AL) display poor cognitive assimilation of thoughts, feelings, and emotions. This may result in the persistence of stress, anxiety, and depressive disorders. The cumulative effect of this psychological distress is also linked clinical markers of human immunodeficiency virus (HIV) disease progression. This study examines the indirect effect of AL on HIV viral load as a function of baseline levels and change in psychological distress. METHODS: N = 123 HIV positive adults aged 37.9 ± 9.2 years provided blood samples for HIV-1 viral RNA and CD4 T lymphocytes along with self-reported stress, anxiety, and depression every 6 months for 2 years. A second-order conditional latent growth model was used to represent baseline and 2-year change in cumulative levels of psychological distress and to test the indirect effect of baseline levels of trait AL on change in HIV-1 viral load through this latent measure. RESULTS: AL was associated with baseline and latent change in psychological distress. Furthermore, baseline psychological distress predicted 2-year change in HIV-1 viral RNA after controlling for viral load at baseline. Altogether, trait AL had a significant indirect effect on change in viral load (ß = 0.16, p = 0.03) as a function of baseline levels of distress. CONCLUSION: Identification and communication of thoughts, feelings, and emotions are important for long-term psychological adaptation in HIV. Greater psychological distress, in turn, allows for persistence of peripheral viral replication.

Alexithymia, Assertiveness and Psychosocial Functioning in HIV: Implications for Medication Adherence and Disease Severity.

Psychosocial function and adherence to antiretroviral regimen are key factors in human immunodeficiency virus (HIV) disease management. Alexithymia (AL) is a trait deficit in the ability to identify and describe feelings, emotions and bodily sensations. A structural equation model was used to test whether high levels of AL indirectly relate to greater non-adherent behavior and HIV disease severity via psychosocial dysfunction. Blood draws for HIV-1 viral load and CD4 T-lymphocyte, along with psychosocial surveys were collected from 439 HIV positive adults aged 18-73 years. The structural model supports significant paths from: (1) AL to non-active patient involvement, psychological distress, and lower social support, (2) psychological distress and non-active involvement to non-adherent behavior, and (3) non-adherence to greater HIV disease severity (CFI = .97, RMSEA = .04, SRMR = .05). A second model confirmed the intermediary effect of greater patient assertiveness on the path from AL to social support and non-active patient involvement (CFI = .94, RMSEA = .04, SRMR = .05). Altogether, AL is indirectly linked with HIV disease management through it's association with poor psychosocial function, however greater patient assertiveness buffers the negative impact of AL on relationship quality with healthcare providers and members of one's social support network.

A meta-analysis of HIV and heart rate variability in the era of antiretroviral therapy.

BACKGROUND: Heart rate variability (HRV) has been used to assess autonomic dysfunction since the beginning of the HIV epidemic. Although autonomic failure was commonly detected in HIV and AIDS patients prior to the advent of antiretroviral therapy (ART), the effect of HIV on HRV in the current era of widespread ART availability is more ambiguous. METHODS: A systematic search and review was conducted on cross-sectional observational and case-control studies published in the era of ART (1996-2015) that compared HRV between HIV + individuals treated with ART and HIV - controls. Eight out of the 20 studies identified, enrolling a total of 292 HIV + adults (mean age 38.7 years) and 201 HIV seronegative controls (mean age 35.1 years), were included in a meta-analysis based on stringent methodological criteria. RESULTS: At rest, individuals with HIV showed lower HRV in the time (g) = -0.72, 95 % CI (-1.03 to -0.42) and low-frequency (LF) domain (g) = -0.51, (-0.81 to -0.21); markers of lower parasympathetic tone in the time (g) = -0.55, (-0.85 to -0.25) and high-frequency (HF) domain (g) = -0.42, (-0.71 to -0.12); and higher LF:HF ratio (g) = 0.46, (0.12-0.86) in the frequency domain, suggestive of parasympathetic withdrawal. CONCLUSION: This meta-analysis confirmed, within a relatively young cohort of HIV + adults on ART, a general reduction in autonomic function with a shift toward sympathetic dominance. This shift may predispose HIV patients to early and elevated risk of arrhythmias, cardiac events, and accelerated HIV disease progression.

The ABCs of Trait Anger, Psychological Distress, and Disease Severity in HIV.

BACKGROUND: Trait anger consists of affective, behavioral, and cognitive (ABC) dimensions and may increase vulnerability for interpersonal conflict, diminished social support, and greater psychological distress. The concurrent influence of anger and psychosocial dysfunction on Human Immunodeficiency Virus (HIV) disease severity is unknown. PURPOSE: The purpose of this study was to examine plausible psychosocial avenues (e.g., coping, social support, psychological distress), whereby trait anger may indirectly influence HIV disease status. METHODS: Three hundred seventy-seven HIV seropositive adults, aged 18-55 years (58% AIDS-defined), completed a battery of psychosocial surveys and provided a fasting blood sample for HIV-1 viral load and T lymphocyte count assay. RESULTS: A second-order factor model confirmed higher levels of the multidimensional anger trait, which was directly associated with elevated psychological distress and avoidant coping (p<.001) and indirectly associated with greater HIV disease severity (p<.01) (comparative fit index (CFI)=0.90, root-mean-square error of approximation (RMSEA)=0.06, standardized root-mean-square residual (SRMR)=0.06). CONCLUSION: The model supports a role for the ABC components of anger, which may negatively influence immune function through various psychosocial mechanisms; however, longitudinal study is needed to elucidate these effects.

Negative attention bias and processing deficits during the cognitive reappraisal of unpleasant emotions in HIV+ women.

Deficits in emotional processing may be attributed to HIV disease or comorbid psychiatric disorders. Electrocortical markers of emotional attention, i.e., amplitude of the P2 and late positive potential (LPP), were compared between 26 HIV+ women and 25 healthy controls during an emotional regulation paradigm. HIV+ women showed early attention bias to negative stimuli indexed by greater P2 amplitude. In contrast, compared with the passive viewing of unpleasant images, HIV+ women demonstrated attenuation of the early and late LPP during positive reappraisal. This interaction remained significant after adjusting for individual differences in apathy, anxiety, and depression. Post hoc analyses implicated time since HIV diagnosis with LPP attenuation during positive reappraisal. Advancing HIV disease may disrupt neural generators associated with the cognitive reappraisal of emotions independent of psychiatric function.

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.

The central executive network moderates the relationship between posttraumatic stress symptom severity and gastrointestinal related issues.

Although most adults experience at least one traumatic event in their lifetime, a smaller proportion will go on to be clinically diagnosed with post-traumatic stress disorder (PTSD). Persons diagnosed with PTSD have a greater likelihood of developing gastrointestinal (GI) disorders. However, the extent to which subclinical levels of post-traumatic stress (PTS) correspond with the incidence of GI issues in a normative sample is unclear. Resting state fMRI, medical history, psychological survey, and anthropometric data were acquired from the Enhanced Nathan Kline Institute-Rockland Sample (n = 378; age range 18-85.6 years). The primary aim of this study was to test the main effect of subclinical PTS symptom severity on the number of endorsed GI issues. The secondary aim was to test the moderating effect of high versus low resting state functional connectivity (rsFC) of the central executive network (CEN) on the relationship between PTS symptom severity and GI issues. Trauma Symptom Checklist-40 (TSC-40) scores were positively associated with the number of endorsed GI issues (b = -0.038, SE = .009, p < .001). The interaction between TSC-40 scores and rsFC within the CEN was significant on GI issues after controlling for sociodemographic and cardiometabolic variables (b = -0.031, SE = .016, p < .05), such that above average rsFC within the CEN buffered the effect of TSC-40 scores on GI issues. Our findings of higher rsFC within the CEN moderating the magnitude of coincidence in PTS and GI symptom severity may reflect the mitigating role of executive control processes in the putative stress signaling mechanisms that contribute to gut dysbiosis.

Synergistic effects of high early-life stress exposure and HIV infection on reaction time variability.

Addressing comorbidities contributing to cognitive impairment in people living with HIV (PLWH) remains imperative. Prior studies utilizing reaction time intra-individual variability (RT-IIV), a robust behavioral marker of cognitive dysfunction, demonstrate increased cognitive impairment in adults living with HIV who have high early life stress (ELS) exposure relative to those with low-ELS exposure. Yet, it is unknown whether RT-IIV elevations are due to high-ELS alone or both HIV-status and high-ELS. In the current study, we explore the potential additive effects of HIV and high-ELS exposure on RT-IIV to better characterize the independent and combined effects of these factors on RT-IIV among PLWH. We assessed 59 PLWH and 69 HIV-negative healthy control (HC) participants with either low or high ELS on RT-IIV during a working memory task (1-back). We observed a significant interaction between HIV status and ELS exposure on RT-IIV, PLWH who had experienced high ELS demonstrating RT-IIV elevations relative to all other groups. In addition, RT-IIV was significantly associated with ELS exposure in PLWH, but not in the HC group. We also observed associations between RT-IIV and measures of HIV-disease severity (plasma HIV viral load, nadir CD4) among PLWH. Taken as a whole, these findings provide novel evidence of the combined effects of HIV and high-ELS exposure on RT-IIV, and thus suggest HIV-related and ELS-related neural abnormalities may act in an additive or synergistic manner to affect cognition. Such data warrant further investigation into the neurobiological mechanisms associated with HIV and high-ELS exposure that contribute to increased neurocognitive dysfunction among PLWH.

Stress and coping in women living with HIV: a meta-analytic review.

To examine effects between stressors and coping mechanisms on behavioral health outcomes a meta-analysis was conducted using forty empirical articles which sampled 7,602 adult women living with HIV/AIDS in the U.S. (M = 36.3 years). Three independent reviewers conducted searches in abstract databases from 1997 to present day. Articles reporting effect sizes amongst psychosocial stressors and coping mechanisms with indices of behavioral/mental health were selected. The meta-analyses revealed that in a time frame characterized by the widespread availability of anti-retroviral medication, poor mental health outcomes were predicted, in a similar manner, by psychosocial stress and HIV/AIDS symptomology. Significant effects were also observed with functional impairment, though to a lesser degree. Coping by avoidance and social isolation predicted more severe mental health outcomes. Spirituality and positive reappraisal predicted greater psychological adaptation than did social support seeking. Despite advancements in anti-retroviral treatment for women, HIV/AIDS symptoms and acute and/or chronic psychosocial stress pose the same threat to behavioral and mental health. In the face of these stressors, positive reframing appears to promote psychological adaptation in a way which may lead to positive health outcomes in women living with HIV/AIDS.

Neutrophil to lymphocyte ratio is a transdiagnostic biomarker of depression and structural and functional brain alterations in older adults.

The neutrophil to lymphocyte ratio (N:L) is an emergent transdiagnostic biomarker shown to predict peripheral inflammation as well as neuropsychiatric impairment. The afferent signaling of inflammation to the central nervous system has been implicated in the pathophysiology of sickness behavior and depression. Here, the N:L was compared to structural and functional limbic alterations found concomitant with depression within a geriatric cohort. Venous blood was collected for a complete blood count, and magnetic resonance imaging as well as phenotypic data were collected from the 66 community-dwelling older adults (aged 65-86 years). The N:L was regressed on gray matter volume and resting-state functional connectivity (rsFC) of the subgenual anterior cingulate (sgACC). Thresholded parameter estimates were extracted from structural and functional brain scans and bivariate associations tested with scores on the geriatric depression scale. Greater N:L predicted lower volume of hypothalamus and rsFC of sgACC with ventromedial prefrontal cortex. Both parameters were correlated (p < 0.05) with greater symptomology in those reporting moderate to severe levels of depression. These findings support the N:L as a transdiagnostic biomarker of limbic alteration underpinning mood disturbance in non-treated older adults.

Association of cardiometabolic health factors with age-related executive function and episodic memory.

Although decline of cognitive abilities in late life is regarded as a common facet of aging, there is inter-individual variability in this decline. Possible contributors are cardiometabolic risk factors associated with cerebrovascular dysfunction, but a dearth in unifying health-cognition models confound exactly how these risk factors mediate age-related changes in executive function (EF) and episodic memory. This study investigated the indirect effect of age on these cognitive abilities via cardiometabolic risk factors using a structural equation modeling approach. Participants included 738 adults (64% female) ranging from 21 to 85 years of age (M = 47.47, SD = 18.28). An exploratory factor analysis was applied to an EF battery yielding a two-factor solution, consisting of inhibition and cognitive flexibility, that showed acceptable fit (χ2(48) = 101.84, p < .001, CFI = .980, RMSEA = .039, SRMR = .035). The EF latent factors were then included in a confirmatory factor analysis exploring the indirect role of age on episodic memory and EF via blood pressure, cholesterol, triglycerides and body mass index. The theoretical model demonstrated acceptable fit, χ2(108) = 204.071, p < .001, CFI = .972, RMSEA = .035, SRMR = .035. Blood pressure was associated with lower cognitive flexibility (ß = -.20, p < .001) and there was a significant indirect effect of age on episodic memory through cognitive flexibility (ß = .07, p = .021). Results support the "Executive Decline Hypothesis" of age-related episodic memory decline and specifically implicate lower blood pressure control and cognitive flexibility in these changes.

Brainstem network connectivity with mid-anterior insula predicts lower systolic blood pressure at rest in older adults with hypertension.

Central regulation of heart rate and blood pressure provides the bases for a neurogenic mechanism of hypertension (HTN). Post menopause (PM) age coincides with changes in resting state functional brain connectivity (rsFC) as well as increased risk for HTN. Whether the neural networks underpinning cardioautonomic control differ between PM women with and without HTN is unclear. Phenotypic and functional neuroimaging data from the Nathan Kline Institute was first evaluated for group differences in intrinsic network connectivity between 22 HTN post menopausal women and 22 normotensive controls. Intrinsic rsFC of the midbrain-brainstem-cerebellar network with bilateral mid-anterior insula was lower in women with HTN (FWE-corrected, p < 0.05). Z-scores indicating rsFC of these regions were extracted from the 44 PM women and a cohort of 111 adults, not presenting with metabolic or neurodegenerative disease, and compared to in-office systolic and diastolic blood pressure. Lower rsFC of the left (r  = -0.17, p = 0.019) and right (r  = -0.14, p = 0.048) mid-anterior insula with brainstem nuclei was associated with higher systolic blood pressure in the combined sample. The magnitude of this effect in men and women of post menopausal age supports a neurogenic mechanism for blood pressure regulation in older adults with HTN.

Paradoxical effect of cumulative stress exposure on information processing speed in Hispanics/Latinos with elevated heart rate variability.

Chronic stress has a deleterious effect on prefrontal lobe functioning. Empirical evidence suggests elevated vagal tone, indexed by elevated heart rate variability (HRV), mitigates the effect of mental stress on frontal lobe function. Here, the mitigating effect of HRV on stress-related decrements in cognitive performance is assessed based on information processing speed (DSST), word fluency and verbal learning task performance. Artifact free electrocardiogram (ECG) data was analyzed from 1420 Hispanic/Latino adults from the Sociocultural Ancillary of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). A 12-lead ECG was used to collect short-term recordings of the root mean square of successive differences in all normal R-peak to R-peak intervals (RMSSD) and the change between adjacent beats and the standard deviation of those intervals (SDNN) as indices of total HRV. As predicted, an interaction emerged for HRV and stress on the task presumed to require the greatest prefrontal lobe involvement, i.e., the DSST. After accounting for sociodemographic factors, chronic stress was associated with better DSST performance amongst individuals at higher quartile of SDNN, but not RMSSD. The paradoxical effect for greater stress exposure on DSST performance may in part be explained by increased speed of information processing and decision making often reported in high-stress cohorts. The nature of this interaction highlights the importance of examining the relationship between stress and cognition across a spectrum of vagal tone.

Do religious and spiritual identity confer risk for hypertension via psychosocial and lifestyle factors?

The total and indirect effect of hostility on systolic and diastolic blood pressure was compared as a function of religious and spirituality identity in a nationally representative sample of 2971 adults aged 46.44 years. Structural equation modeling uncovered an indirect path from hostility to diastolic blood pressure via unhealthy behaviors and hostility to unhealthy behaviors via social isolation. Compared to a non-religious/non-spiritual reference group, the effect for unhealthy behaviors on diastolic blood pressure was greater for those endorsing some form of religious identity. However, the direction of the effect for hostility on social isolation and social isolation on unhealthy behaviors was reversed in those endorsing spiritual and religious identity.