Combined effects of loneliness and inflammation on depression in people with HIV.

OBJECTIVE: Loneliness is prevalent in people with HIV (PWH) and associated with adverse health-related consequences, including depression. Chronic inflammation has been linked to depression in PWH, though its association with loneliness is less well established. Simultaneous examination of inflammation, loneliness and depression is needed to clarify these relationships. This study investigated the relationship between loneliness and inflammation, and the effects of loneliness and inflammation on depression in PWH. METHODS: 82 PWH who were on suppressive ART (mean age [SD] = 53.2 [9.0]) completed the UCLA Loneliness Scale-Version 3 and the Center for Epidemiologic Studies Depression Scale as part of a comprehensive evaluation. Biomarkers of systemic inflammation (CRP, IL-6, CCL2/MCP-1, sCD14) and coagulation (D-dimer) were measured in blood using commercial immunoassays. RESULTS: Multivariable linear regression analyses revealed that higher D-dimer, CCL2/MCP-1, and sCD14 were significant predictors of loneliness (ps < .05) while accounting for relevant covariates. Stepwise multiple linear regression models that included loneliness, biomarkers, and their interactions as predictors of depressive symptoms revealed significant main effects of loneliness and CCL2/MCP-1 levels (ps < .05), and a significant loneliness by D-dimer interaction (p < .05) whereby higher D-dimer was associated with increased depressive symptoms only at higher levels of loneliness. CONCLUSIONS: Increased coagulation activity is associated with loneliness, and in the context of loneliness, may increase risk for depression. Increased inflammation was associated with depression suggesting potentially dissociable underlying biological processes. To the extent that these processes are modifiable, such findings could have important implications in the treatment of loneliness and depression in PWH.

The impact of life stress, psychological resources, and proactive behaviors on quality of life among people living with HIV.

OBJECTIVES: Quality of life (QoL) is an important consideration for people living with HIV (PWH). We investigated the relationship between stress, psychological resources, and proactive behaviors, on QoL (conceptualized as life satisfaction, successful aging, and depressive symptoms) by testing the hypotheses: (1) greater life stress (stress and functional impairment) is associated with poorer QoL; (2) resources (mastery, resilience, and social support) are associated with better QoL, beyond the influence of stress; and (3) proactive behaviors (medication management and leisure activities) mediate the relationship between resources and QoL. METHODS: Secondary analyses were performed (N = 128 PWH). Participants' mean age was 52.3, 83.6% were male, and 53.9 identified as white. Multivariate regressions were performed within the context of path analyses. RESULTS: In series 1, greater stress was associated with poorer life satisfaction (p < 0.001), lower self-rated successful aging (p < 0.001), and greater depression (p < 0.001). Functional impairment was associated with lower successful aging (p = 0.017) and greater depression (p = 0.001). In series 2, which accounted for mastery, resilience, social support, as well as demographic covariates, mastery was associated with greater life satisfaction (p = 0.038). In series 3, stress, functional impairment, leisure activities, and ART management were added to the model and social support was associated with engagement in leisure activities (p < 0.001), which was associated with better successful aging (p = 0.006). Fit indices suggested adequate relative fit. In bootstrapped analyses of indirect effects, social support was indirectly associated with successful aging through leisure activities (p = 0.020). CONCLUSIONS: QoL, as captured by self-rated successful aging, is threatened by stress but positively influenced by social support and engaging in leisure activities. Findings support a model of proactive successful aging for PWH.

Loneliness in Posttraumatic Stress Disorder: A Neglected Factor in Accelerated Aging?

Prior research suggests that people with Posttraumatic Stress Disorder (PTSD) may experience a form of accelerated biological aging. In other populations, loneliness has been shown to elevate risk for many of the same components of accelerated biological aging, and other deleterious outcomes, as seen in people with PTSD. Although standard diagnostic criteria for PTSD include "feelings of detachment or estrangement from others", the relationship of such feelings to the concept of loneliness remains uncertain, in par potentially due to a failure to distinguish between loneliness versus objective social isolation. In order to catalyze wider research attention to loneliness in PTSD, and the potential contribution to accelerated biological aging, the present paper provides three components: (1) a conceptual overview of the relevant constructs and potential interrelationships, (2) a review of the limited extant empirical literature, and (3) suggested directions for future research. The existing empirical literature is too small to support many definitive conclusions, but there is evidence of an association between loneliness and symptoms of PTSD. The nature of this association may be complex, and the causal direction(s) uncertain. Guided by the conceptual overview and review of existing literature, we also highlight key areas for further research. The ultimate goal of this line of work is to elucidate mechanisms underlying any link between loneliness and accelerated aging in PTSD, and to develop, validate, and refine prevention and treatment efforts.

Relationship of the balloon analog risk task to neurocognitive impairment differs by HIV serostatus and history of major depressive disorder.

HIV and major depressive disorder (MDD) commonly co-occur and are both linked to greater risk-taking behavior, possibly due to neurocognitive impairment (NCI). The present study examined the concordance of the Balloon Analog Risk Task (BART), a gold standard measure of risk-taking propensity, with NCI and real-world sexual risk behaviors in PWH with comorbid MDD. Participants included 259 adults, stratified by HIV serostatus (HIV + /HIV -) and lifetime MDD (MDD + /MDD -), who completed neuropsychological testing, the BART, and sexual risk behavior questionnaires. Logistic regression, stratified by HIV serostatus, examined joint effects of MDD and BART (linear and quadratic) on NCI. Follow-up linear regressions examined sexual risk behavior and neurocognitive domain T-scores as correlates of the BART. NCI prevalence was lowest in HIV - /MDD - , but BART scores did not differ by HIV/MDD status. In the HIV + group, BART performance predicted NCI such that high and low BART scores related to greater odds of NCI, but only in dual-risk HIV + /MDD + individuals. HIV + /MDD + individuals with both low and high BART scores exhibited poorer learning and recall, whereas processing speed and executive function were only poor in low BART risk-taking HIV + /MDD + . Higher BART scores linearly related to higher sexual risk behaviors only in MDD + individuals, independent of HIV serostatus. Low and high risk-taking on the BART may reflect discrete neurocognitive profiles in HIV + /MDD + individuals, with differential implications for real-world sexual risk behavior. HIV and comorbid MDD may disturb corticostriatal circuits responsible for integrating affective and neurocognitive components of decision-making, thereby contributing to risk-averse and risk-taking phenotypes.

Ethnic/Racial Disparities in Longitudinal Neurocognitive Decline in People With HIV.

BACKGROUND: To examine longitudinal neurocognitive decline among Latino, non-Latino Black, and non-Latino White people with HIV (PWH) and factors that may explain ethnic/racial disparities in neurocognitive decline. METHODS: Four hundred ninety nine PWH (13.8% Latino, 42.7% Black, 43.5% White; baseline age: M = 43.5) from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study completed neurocognitive, neuromedical, and laboratory assessments every 6-12 months with up to 5 years of follow-up. Longitudinal neurocognitive change was determined via published regression-based norms. Survival analyses investigated the relationship between ethnicity/race and neurocognitive change, and baseline and time-dependent variables that may explain ethnic/racial disparities in neurocognitive decline, including socio-demographic, HIV-disease, medical, psychiatric, and substance use characteristics. RESULTS: In Cox proportional hazard models, hazard ratios for neurocognitive decline were increased for Latino compared with White PWH (HR = 2.25, 95% CI = 1.35 to 3.73, P = 0.002), and Latino compared with Black PWH (HR = 1.86, 95% CI = 1.14 to 3.04, P = 0.013), with no significant differences between Black and White PWH (P = 0.40). Comorbidities, including cardiometabolic factors and more severe neurocognitive comorbidity classification, accounted for 33.6% of the excess hazard for Latino compared with White PWH, decreasing the hazard ratio associated with Latino ethnicity (HR = 1.83, 95% CI = 1.06 to 3.16, P = 0.03), but did not fully account for elevated risk of decline. CONCLUSIONS: Latino PWH may be at higher risk of early neurocognitive decline compared with Black and White PWH. Comorbidities accounted for some, but not all, of this increased risk among Latino PWH. Future research examining institutional, sociocultural, and biomedical factors, including structural discrimination and age-related biomarkers, may further explain the observed disparities.

Loneliness, Risky Beliefs and Intentions about Practicing Safer Sex among Methamphetamine Dependent Individuals.

BACKGROUND: Methamphetamine use is a known predictor of riskier sexual behaviors, which can have important public health implications (e.g., HIV-transmission risk). Loneliness also is associated with riskier sexual behaviors, though the relationship between loneliness and beliefs and/or intentions to practice safer sex has not been examined among people dependent on methamphetamine. MATERIALS AND METHODS: Individuals who met DSM-IV criteria for lifetime methamphetamine dependence and current (≤ 18-months) methamphetamine abuse or dependence (METH+ n = 56) were compared to those without severity and recency of methamphetamine use (METH- n = 59). These groups did not differ on social network size or proportion of people with HIV (∼58% HIV+). Participants completed the NIH Toolbox Loneliness Scale and the Sexual Risks Scale's "Norms" and "Intentions" subscales. RESULTS: METH+ individuals were significantly lonelier than METH- controls (t(113) = 2.45, p = .02). Methamphetamine dependence remained significantly associated with greater loneliness, after controlling for HIV status and other relevant covariates (e.g., neurocognitive impairment, history of mood disorder, social network size; F = 3.70, Adjusted R2 = 0.18, p = .0009). Loneliness, above and beyond the aforementioned covariates, was significantly associated with riskier beliefs and intentions to practice safer sex among METH+, but not METH-, individuals (ß = 2.92, p = .02). CONCLUSIONS: Loneliness is prevalent among individuals dependent on methamphetamine, and is uniquely associated with riskier beliefs and intentions regarding practicing safer sex. Findings may aid in identifying individuals at-risk of engaging in riskier sexual behaviors and guide risk prevention strategies.

Apathy is associated with poorer abstinence self-efficacy in individuals with methamphetamine dependence.

BACKGROUND: Confidence in one's ability to achieve and maintain drug abstinence (i.e., abstinence self-efficacy) is a strong predictor of substance use treatment outcomes. Neurobehavioral factors that may interfere with abstinence self-efficacy are less well established, particularly in methamphetamine (METH). This study investigated whether apathy, which is highly prevalent during active METH use and periods of abstinence, influences abstinence self-efficacy among METH dependent individuals. METHODS: Sixty-six participants with lifetime METH dependence and METH abuse/METH dependence diagnoses within the last 18 months (mean age [SD] = 39.5 years [10.7]), and no severe psychiatric or neurological diseases, completed the Methamphetamine Self-Efficacy Scale (MSES), alongside a comprehensive neurobehavioral evaluation. The MSES presents six situations that may lead to relapse and collects self-report ratings for two subscales: "Confidence" (i.e., confidence in one's ability to abstain from using METH, or METH abstinence self-efficacy) and "Temptation" (i.e., how tempted one is to use METH) with regard to each situation. Apathy was measured using a composite T-score comprised of items and scales from three well-validated, self-report assessments. RESULTS: Multivariable linear regression found that higher Apathy T-scores were significantly associated with lower Confidence ratings (i.e., poorer METH abstinence self-efficacy; p < .05), independent of potentially relevant factors (e.g., Temptation to use METH, comorbid HIV disease, and neurocognitive impairment). CONCLUSIONS: Elevated apathy may adversely impact one's confidence to abstain from METH use. Findings highlight the importance of addressing apathy in order to improve METH abstinence self-efficacy, which may subsequently increase the likelihood of successful METH treatment outcomes.

Neurocognitive impairment in Spanish-speaking Latinos living with HIV in the US: Application of the neuropsychological norms for the US-Mexico border region in Spanish (NP-NUMBRS).

Objective Latinos in the US are at increased risk for HIV-associated neurocognitive impairment (NCI). Most studies of US Latinos living with HIV have included primarily English-speakers only. We investigated the rate, pattern, and correlates of HIV-associated NCI in native Spanish-speaking Latinos living in the US near the Mexican border. Methods Participants included 407 native Spanish-speaking Latinos (Age: M = 37.65, SD = 10.0; Education: M = 10.75, SD = 4.1; 53% male): 153 persons living with HIV (PLWH; 56% AIDS) and 254 healthy controls. All participants completed comprehensive neuropsychological assessments in Spanish. Raw neuropsychological test scores from seven domains were converted to demographically-adjusted T-scores using norms developed with healthy controls. Global and domain NCI were defined per established criteria. Among PLWH we applied norms developed for non-Hispanic (NH) Whites and Blacks, and investigated correlates of global NCI, including HIV disease characteristics and psychiatric comorbidities. Results Utilizing population specific norms, rates of global NCI were significantly higher among PLWH (39%) than healthy controls (17%), comparable to previously published rates. In contrast, rates of global NCI in the same group of PLWH were significantly different when NH White norms (63%, p < 0.0001) and NH Black norms were used (18%, p < 0.0001). Among PLWH without a history of lifetime substance use disorder, more years of antiretroviral exposure were significantly associated with decreased rates of global NCI. Conclusions Present findings lend support to the validity of newly developed norms for native Spanish-speakers living near the US-Mexico border, and underscore the importance of utilizing appropriate norms to accurately identify HIV-associated NCI.

Metabolic Risk Factors as Differential Predictors of Profiles of Neurocognitive Impairment Among Older HIV+ and HIV- Adults: An Observational Study.

OBJECTIVE: Neurocognitive performance among older persons, including those living with HIV (people living with HIV [PLWH]), exhibits significant heterogeneity, suggesting subpopulations with differing profiles of neurocognitive impairment (NCI). Metabolic factors are associated with NCI, but their relationships to cluster-derived NCI profiles are unknown. METHOD: Participants (144 PLWH and 102 HIV uninfected) aged 50+ years completed a neuropsychological battery assessing seven cognitive domains. Latent class analysis (LCA) identified NCI profiles separately by HIV serostatus and in a combined sample. Obtained classes were examined against the Montreal Cognitive Assessment (MoCA) and diagnoses of HIV-associated neurocognitive disorders (HAND). Multinomial regression identified metabolic predictors of classification. RESULTS: LCA identified three latent classes in each participant sample: Class1Multidomain NCI (high probability of impairment across multiple domains), Class 2Learning & Recall NCI (high probability of impairment in learning and recall), and Class 3NC Unimpaired (low probability of NCI across all domains). Severity of NCI implied by classes corresponded with MoCA scores and HAND diagnoses. In analyses on the combined sample, compared to HIV-uninfected individuals, PLWH were more likely to be in Class1Multidomain NCI. Among PLWH, those with dyslipidemia and hypertension had greater odds of classification in Class 1Multidomain NCI while those with central obesity had higher odds of classification in Class 2Learning & Recall NCI; metabolic syndrome approached significance as a differential predictor. Regardless of HIV status, individuals with diabetes were more likely to be in Class 1Multidomain NCI. CONCLUSIONS: Metabolic risk factors confer heightened risk of NCI in HIV infection. Interventions to reduce metabolic risk may improve neurocognitive outcomes among PLWH.

Inflammation-related genes are associated with epigenetic aging in HIV.

Chronic inflammation is characteristic of both HIV and aging ("inflammaging") and may contribute to the accelerated aging observed in people living with HIV (PLWH). We examined whether three inflammation-related single-nucleotide polymorphisms (SNPs) were risk factors for accelerated aging and HIV-associated, non-AIDS (HANA) conditions among PLWH. We examined 155 postmortem cases with HIV (mean age = 47.3, 81% male, 68% self-reported White) from the National NeuroAIDS Tissue Consortium who had pre-mortem neurobehavioral/medical/virologic data and epigenomic data from occipital cortex tissue. Accelerated aging was measured according to the Epigenetic Clock; an aging biomarker based on DNA methylation levels. Past or current age-associated HANA conditions including cerebrovascular, liver and kidney disease, chronic obstructive pulmonary disease, cancer, and diabetes were determined via self-report. Epigenetic Aging Z-scores and likelihood of past/current HANA conditions were compared between major allele homozygotes and minor allele carriers for each SNP (IL-6 - 174G>C, IL-10 - 592C>A, TNF-α - 308 G>A) separately. Analyses were adjusted for relevant demographic/clinical factors. Epigenetic aging (e.g., higher Z-scores) was significantly greater in IL-6 C allele carriers (p = .002) and IL-10 CC homozygotes (p = .02) compared to other genotype groups. The likelihood of any past/current HANA condition did not differ by IL-10 genotype but was 3.36 times greater in IL-6 C allele carriers versus others (OR = 3.36, 95%CI = 1.09-10.34, p = .03). TNF-α genotype was not associated with epigenetic aging or HANA conditions. IL-6 and IL-10 SNPs may help to identify PLWH who are at high risk for accelerated aging. These insights into pathophysiological pathways may inform interventional approaches to treat rapid aging among PLWH.

Effects of trauma, economic hardship, and stress on neurocognition and everyday function in HIV.

OBJECTIVE: The causes of neurocognitive and everyday functioning impairment among aging people living with HIV (PLWH) are multifactorial. Exposure to stress and trauma can result in neurocognitive deficits via activation of neurological and other biological mechanisms. METHOD: PLWH (n = 122) and persons without HIV (n = 95), 35-65 years of age, completed four questionnaires that were used to generate a trauma, economic hardship (food insecurity and low socioeconomic status), and stress composite variable (TES). Participants also completed a comprehensive neuropsychological battery and standardized self-reports of activities of daily living (ADLs). We examined the independent and interactive effects of TES and HIV status on neurocognitive performance and ADL declines. RESULTS: PLWH had more traumatic events, more food insecurity, lower socioeconomic status, and higher perceived stress compared with HIV- individuals (all ps < .0001). Among PLWH, a higher composite TES score was associated with worse executive functioning (p = .02), worse learning (p = .02), worse working memory (p = .02), and more ADL declines (p < .0001), even after controlling for relevant demographic, psychiatric, substance use, and HIV disease covariates. On their own, individual TES components did not predict these outcomes. Conversely, no significant relationships were observed between TES and cognitive domains nor ADL declines among HIV- individuals. CONCLUSIONS: A composite score of trauma, economic hardship, and stress was significantly associated with worse neurocognitive performance and functional declines among PLWH. These adverse experiences may contribute to neurocognitive and daily functioning difficulties commonly observed among PLWH. Longitudinal studies are needed to elucidate the relationships between economic/psychosocial adversities and cognitive/functional outcomes over time, and examine potential mediators, such as inflammatory biomarkers. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Grit and Ambition are Associated with Better Neurocognitive and Everyday Functioning Among Adults Living with HIV.

Grit and ambition are psychological factors that may protect neurocognitive function among persons living with HIV (PLWH). We examined associations between grit, ambition, premorbid verbal intellectual function, and current neurocognitive and everyday functioning among PLWH and persons without HIV (HIV-). 120 PLWH and 94 HIV- adults completed the Grit Scale (includes total score and consistency of interests and perseverance of effort subscales), ambition scale, and a comprehensive neurobehavioral battery. PLWH had lower grit scores than HIV- adults. The two groups did not differ on ambition. No relationship was observed between grit and cognition among HIV- adults. Among PLWH, however, higher perseverance of effort and more ambition was related to better global neurocognitive functioning, and higher grit, but not ambition, was related to independence in daily functioning. Longitudinal studies are needed to elucidate these relationships over time and examine whether grit or ambition have protective effects on cognitive outcomes among PLWH.

The role of emotion regulation and cognitive control in the association between mindfulness disposition and stress.

Dispositional mindfulness is associated with lower levels of perceived stress, with increased emotional regulation and cognitive control proposed as mechanisms underlying these stress-buffering effects of mindfulness. Within aging, these controlled processes represent paradoxically divergent trajectories such that older adults exhibit reduced cognitive control capacities, while emotional regulation abilities are well maintained, and at times enhanced. Our study seeks to examine the role of emotional regulation and cognitive control as possible mediators of the association between mindfulness and perceived stress. In addition, we examined age-related differences in the observed associations among mindfulness, stress, and controlled regulatory behavior. Fifty older adults and fifty young adults were recruited for the study and completed self-report measures assessing mindfulness disposition, perceived stress, and emotional regulation. In addition, computerized measures of cognitive control assessing working memory, inhibitory control, and set-shifting were also administered. We hypothesized a negative correlation between mindfulness disposition and perceived stress such that participants reporting higher levels of dispositional mindfulness would report lower stress. In addition, we hypothesized increased difficulties in emotion regulation and lower cognitive control to mediate this relationship. Corroborating previous literature, results revealed that mindfulness disposition and perceived stress were negatively correlated in both groups. However, emotion regulation, but not cognitive control, was found to mediate the relationship between mindfulness and perceived stress in both groups. Age group was not found to moderate the observed effects. Our findings reveal the role of enhanced emotional regulation abilities as a potential factor associated with the stress-reducing capacity of dispositional mindfulness.