Links Between Inflammation, Mood, and Physical Function Among Older Adults With HIV.

OBJECTIVES: People living with human immunodeficiency virus (PLWH) treated with antiretrovirals have life spans similar to their HIV-negative peers. Yet, they experience elevated inflammation-related multimorbidity. Drawing on biopsychosocial determinants of health may inform interventions, but these links are understudied in older PLWH. We investigated cross-sectional relationships between psychosocial factors (mood, loneliness, and stigma), inflammatory markers, and age-related health outcomes among 143 PLWH aged 54-78 years. METHOD: Participants provided blood samples for serum cytokine and C-reactive protein (CRP) analyses, completed surveys assessing psychosocial factors and health, and completed frailty assessments. Regression models tested relationships between key psychosocial-, inflammation, and age-related health variables, adjusting for relevant sociodemographic and clinical factors. RESULTS: Participants with more depressive symptoms had higher composite cytokine levels than those with fewer depressive symptoms (ß = 0.22, t(126) = 2.71, p = .008). Those with higher cytokine levels were more likely to be prefrail or frail (adjusted odds ratio = 1.72, 95% confidence interval = 1.01-2.93) and reported worse physical function (ß = -0.23, t(129) = -2.64, p = .009) and more cognitive complaints (ß = -0.20, t(129) = -2.16, p = .03) than those with lower cytokine levels. CRP was not significantly related to these outcomes; 6-month fall history was not significantly related to inflammatory markers. DISCUSSION: Novel approaches are needed to manage comorbidities and maximize quality of life among older PLWH. Illustrating key expected biopsychosocial links, our findings highlight several factors (e.g., depressive symptoms, poorer physical function) that may share bidirectional relationships with chronic inflammation, a key factor driving morbidity. These links may be leveraged to modify factors that drive excessive health risk among older PLWH.

Associations between beta-blocker use and psychological distress in bereaved adults with cardiovascular conditions.

The death of a close other is a major life stressor that disrupts mental and physical health. Beta-blocker medications are indicated treatments for cardiovascular conditions that may also mitigate psychological distress in the context of stressors by reducing adrenergic activity. We sought to examine observational links between beta-blocker medication use and psychological distress during bereavement. Using publicly available data from the Midlife in the United States Refresher study, we examined associations between beta-blocker use and general distress, depressive symptoms, and anxiety symptoms (as measured by the Mood and Anxiety Symptom Questionnaire) among bereaved adults with cardiovascular conditions (n = 161) using t-tests and regression models. Beta-blocker users reported lower levels of anxiety-related general distress (b = -2.49, SE = 0.88, p = 0.005) and depression-related general distress than non-users (b = -2.39, SE = 1.14, p = 0.039) in multivariate linear regression models adjusting for demographic characteristics, mental health treatments, time since loss and comorbid health conditions. These observed links between beta-blockers and lower psychological distress in bereavement warrant further investigation in prospective and randomized studies, as beta-blockers could be a scalable intervention for mitigating distress following loss.

Childhood sexual abuse history amplifies the link between disease burden and inflammation among older adults with HIV.

As they age, people living with HIV (PLWH) experience greater rates of inflammation-related health conditions compared to their HIV-negative peers. Because early life adversity can exaggerate proinflammatory effects of later physiological challenges, inflammation may be higher among PLWH with these combined risks, which could inform intervention approaches to mitigate multimorbidity. In this cross-sectional analysis, we investigated individual and combined effects of childhood sexual abuse (CSA) history and physiological burden (Veterans Aging Cohort Study Index scores) on serum cytokine and C-reactive protein (CRP) levels among PLWH. Participants (n â€‹= â€‹131; age 54 and older) were patients at an outpatient HIV clinic who completed a psychosocial survey and biomedical research visit as part of a larger study. 93% were virally suppressed, and 40% reported experiencing sexual abuse in childhood. Composite cytokine levels (summarizing IL-6, TNF-α, IFN-γ), CRP, and disease burden did not differ significantly between those who had a history of CSA and those who did not. Participants with greater disease burden had higher composite cytokine levels (r â€‹= â€‹0.29, p â€‹= â€‹0.001). The disease burden by CSA interaction effect was a significant predictor of composite cytokine levels (but not CRP), and remained significant after controlling for age, sex, race, BMI, anti-inflammatory medication use, selective serotonin reuptake inhibitor use, depressive symptoms, and smoking status (F(1, 114) â€‹= â€‹5.68, p â€‹= â€‹0.02). In follow-up simple slopes analysis, greater disease burden was associated with higher cytokine levels among those with CSA history (b â€‹= â€‹0.03, SE â€‹= â€‹0.008, p<0.001), but not among those without CSA history. Further, in the context of greater disease burden, individuals with a CSA history tended to have higher cytokine levels than those without a CSA history (b â€‹= â€‹0.38, SE â€‹= â€‹0.21, p â€‹= â€‹0.07). These data suggest that the physiological sequelae of childhood trauma may persist into older age among those with HIV. Specifically, links between physiological burden and inflammation were stronger among survivors of CSA in this study. The combined presence of CSA history and higher disease burden may signal a greater need for and potential benefit from interventions to reduce inflammation, an area for future work.

Urine Cell-Free Mitochondrial DNA as a Marker of Weight Loss and Body Composition in Older Adults With HIV.

BACKGROUND: Older adults with HIV (OAH) experience more comorbidities and geriatric syndromes than their HIV-negative peers, perhaps because of chronic inflammation. Cell-free mitochondrial DNA (cfmtDNA) released from cells undergoing necrosis-mediated cell death potentially acts as both a mediator and marker of inflammatory dysregulation. We hypothesized that urinary cfmtDNA would be associated with frailty, body composition, and fall history in OAH. METHODS: OAH completed frailty testing, a psychosocial survey, body composition assessment, and measurement of urine cfmtDNA and urine albumin:creatinine in this cross-sectional study. Urine cfmtDNA was measured by quantative polymerase chain reaction and normalized to urinary creatinine. RESULTS: Across 150 participants, the mean age was 61 years (SD 6 years), half identified as Black, one-third were women, and 93% had HIV-1 viral load <200 copies/mL. Two-thirds met criteria for a prefrail or frail state. Those with unintentional weight loss had higher urine cfmtDNA concentrations (P = 0.03). Higher urine cfmtDNA was inversely associated with the skeletal muscle index (ß = -0.19, P < 0.01) and fat mass index (ß = -0.08, P = 0.02) in separate multiple linear regression models adjusted for age, sex, and presence of moderate-severe albuminuria. CONCLUSIONS: In this cross-sectional study of OAH, higher levels of urine cfmtDNA were more common in subjects with less robust physical condition, including unintentional weight loss and less height-scaled body mass of fat and muscle. These findings suggest urine cfmtDNA may reflect pathophysiologic aging processes in OAH, predisposing them to geriatric syndromes. Longitudinal investigation of urine cfmtDNA as a biomarker of geriatric syndromes is warranted.

Gait Speed Is Associated with Cognitive Function among Older Adults with HIV.

Objectives: To determine links between objectively and subjectively measured physical function and cognitive function among HIV-positive older adults, a growing yet understudied group with elevated risk for multimorbidity. Methods: At a biomedical research visit, 162 participants completed objective tests of gait speed (4-m walk), grip strength (dynamometer), and cognitive function (Montreal Cognitive Assessment, MoCA) and reported their well-being (Medical Outcomes Study-HIV survey). Results: Those with faster gait speed had better overall cognitive function than those with slower gait speed (b = 3.98, SE = 1.30, p = .003) in an adjusted regression model controlling for age, sex, race, height, preferred language, and assistive device use. Grip strength was not significantly associated with overall cognitive function. Self-rated cognitive function was weakly related to MoCA scores (r = .26) and gait speed (r = .14) but was strongly associated with emotional well-being (r = .53). Discussion: These observed, expected connections between physical and cognitive function could inform intervention strategies to mitigate age-related declines for older adults with HIV.

Palliative Chemotherapy or Radiation and Prognostic Understanding among Advanced Cancer Patients: The Role of Perceived Treatment Intent.

Background: As patients' accurate understanding of their prognosis is essential for informed end-of-life planning, identifying associated factors is important. Objective: We examine if receiving palliative chemotherapy or radiation, and the perception of those treatments as curative or noncurative, is associated with prognostic understanding. Design: Cross-sectional analyses from a multisite, observational study. Setting/Subjects: Patients with advanced cancers refractory to at least one chemotherapy regimen (N = 334). Measurements: In structured interviews, patients reported whether they were receiving chemotherapy or radiation, and whether its intent was curative or not. Their responses were categorized into three groups: patients not receiving chemotherapy/radiation (no cancer treatment group); patients receiving chemotherapy/radiation and misperceiving it as curative (treatment misperception group); and patients receiving chemotherapy/radiation and accurately perceiving it as noncurative (accurate treatment perception group). Patients also reported on various aspects of their prognostic understanding (e.g., life expectancy). Results: Eighty-six percent of the sample was receiving chemotherapy or radiation; of those, 16.7% reported the purpose of treatment to be curative. The no-treatment group had higher prognostic understanding scores compared with the treatment misperception group (adjusted odds ratio [AOR] = 5.00, p < 0.001). However, the accurate treatment perception group had the highest prognostic understanding scores in comparison to the no-treatment group (AOR = 2.04, p < 0.05) and the treatment misperception group (AOR = 10.19, p < 0.001). Conclusions: Depending on patient perceptions of curative intent, receipt of palliative chemotherapy or radiation is associated with better or worse prognostic understanding. Research should examine if enhancing patients' understanding of treatment intent can improve accurate prognostic expectations.

Emotions in the room: common emotional reactions to discussions of poor prognosis and tools to address them.

Introduction: Advanced cancer patients often want prognostic information, and discussions of prognosis have been shown to enhance patient understanding of their illness. Such discussions can lead to high-quality, value-consistent care at the end of life, yet they are also often emotionally challenging. Despite how common and normal it is for patients to experience transient emotional distress when receiving 'bad news' about prognosis, emotional responses have been under-addressed in existing literature on prognostic discussions. Areas covered: Drawing upon psychology research, principles of skilled clinical communication, and published approaches to discussions of serious illness, we summarize patients' common emotional reactions and coping strategies. We then provide suggestions for how to respond to them in clinic. Expert opinion: Ultimately, effective management of emotional reactions to bad news may lead to earlier, more frequent, and more transparent discussions of prognosis, thus promoting cancer patients' understanding of, and adjustment to, their illness and improving the quality of their end-of-life care.

Advanced cancer patients' understanding of prognostic information: Applying insights from psychological research.

PURPOSE: Informed medical decision-making at the end of life often requires engaging in highly emotional, potentially upsetting discussions about prognosis, while ensuring that patients grasp its personal meaning. Behavioral science offers insights into ways to promote prognostic understanding among patients with advanced cancer. SUMMARY: In this literature review, we synthesize complementary findings from basic behavioral science and applied clinical research, which suggest that psychological factors can significantly influence both patients' clinical interactions and their prognostic understanding. For example, stress and emotion can affect cognition, which may shape how patients process complex medical information. Additionally, clinicians may be less likely to share prognostic information with distressed patients who, in turn, may be hesitant to ask about their prognosis for fear of the answer. Although traditional approaches for increasing advanced cancer patients' understanding focus on improving information delivery, these efforts may not be sufficient without corresponding interventions that assist patients in managing distress. CONCLUSIONS: Psychological barriers may limit opportunities for patients to fully understand their prognosis and to receive high quality of end-of-life care that is linked with an accurate understanding of their disease and treatment options. Failure to attend to patients' emotional distress may undermine efforts to improve medical communication. This underscores the importance of increased attention to the psychological factors that impede patients' comprehension of material shared in cancer clinic visits, in order to inform interventions that address patient distress both before and after receiving "bad news." Integrating findings from psychological research into prognostic discussions may not only improve advanced cancer patients' mental health, but may also promote their ability to make informed, value-consistent medical decisions.

Associations between Anxiety, Poor Prognosis, and Accurate Understanding of Scan Results among Advanced Cancer Patients.

Background: Routine imaging ("scan") results contain key prognostic information for advanced cancer patients. Yet, little is known about how accurately patients understand this information, and whether psychological states relate to accurate understanding. Objective: To determine if patients' sadness and anxiety, as well as results showing poorer prognosis, are associated with patients' understanding of scan results. Design: Archival contrasts performed on multi-institutional cohort study data. Subjects: Advanced cancer patients whose disease progressed after at least one chemotherapy regimen (N = 94) and their clinicians (N = 28) were recruited before an oncology appointment to discuss routine scan results. Measurements: In preappointment structured interviews, patients rated sadness and anxiety about their cancer. Following the appointment, patients and clinicians reported whether the imaging results discussed showed progressive, improved, or stable disease. Results: Overall, 68% of patients reported their imaging results accurately, as indicated by concordance with their clinician's rating. Accuracy was higher among patients whose results indicated improved (adjusted odds ratio [AOR] = 4.12, p = 0.02) or stable (AOR = 2.59, p = 0.04) disease compared with progressive disease. Patients with greater anxiety were less likely to report their imaging results accurately than those with less anxiety (AOR = 0.09, p = 0.003); in contrast, those with greater sadness were more likely to report their results accurately than those with less sadness (AOR = 5.23, p = 0.03). Conclusions: Advanced cancer patients with higher anxiety and those with disease progression may need more help understanding or accepting their scan results than others.

Inflammation: depression fans the flames and feasts on the heat.

Depression and inflammation fuel one another. Inflammation plays a key role in depression's pathogenesis for a subset of depressed individuals; depression also primes larger cytokine responses to stressors and pathogens that do not appear to habituate. Accordingly, treatment decisions may be informed by attention to questions of how (pathways) and for whom (predispositions) these links exist, which are the focus of this article. When combined with predisposing factors (moderators such as childhood adversity and obesity), stressors and pathogens can lead to exaggerated or prolonged inflammatory responses. The resulting sickness behaviors (e.g., pain, disturbed sleep), depressive symptoms, and negative health behaviors (e.g., poor diet, a sedentary lifestyle) may act as mediating pathways that lead to further, unrestrained inflammation and depression. Depression, childhood adversity, stressors, and diet can all influence the gut microbiome and promote intestinal permeability, another pathway to enhanced inflammatory responses. Larger, more frequent, or more prolonged inflammatory responses could have negative mental and physical health consequences. In clinical practice, inflammation provides a guide to potential targets for symptom management by signaling responsiveness to certain therapeutic strategies. For example, a theme across research with cytokine antagonists, omega-3 fatty acids, celecoxib, and exercise is that anti-inflammatory interventions have a substantially greater impact on mood in individuals with heightened inflammation. Thus, when inflammation and depression co-occur, treating them in tandem may enhance recovery and reduce the risk of recurrence. The bidirectional links between depression, inflammation, and disease suggest that effective depression treatments could have a far-reaching impact on mood, inflammation, and health.

Sex Differences in Depression: Does Inflammation Play a Role?

Women become depressed more frequently than men, a consistent pattern across cultures. Inflammation plays a key role in initiating depression among a subset of individuals, and depression also has inflammatory consequences. Notably, women experience higher levels of inflammation and greater autoimmune disease risk compared to men. In the current review, we explore the bidirectional relationship between inflammation and depression and describe how this link may be particularly relevant for women. Compared to men, women may be more vulnerable to inflammation-induced mood and behavior changes. For example, transient elevations in inflammation prompt greater feelings of loneliness and social disconnection for women than for men, which can contribute to the onset of depression. Women also appear to be disproportionately affected by several factors that elevate inflammation, including prior depression, somatic symptomatology, interpersonal stressors, childhood adversity, obesity, and physical inactivity. Relationship distress and obesity, both of which elevate depression risk, are also more strongly tied to inflammation for women than for men. Taken together, these findings suggest that women's susceptibility to inflammation and its mood effects may contribute to sex differences in depression. Depression continues to be a leading cause of disability worldwide, with women experiencing greater risk than men. Due to the depression-inflammation connection, these patterns may promote additional health risks for women. Considering the impact of inflammation on women's mental health may foster a better understanding of sex differences in depression, as well as the selection of effective depression treatments.

Yoga and self-reported cognitive problems in breast cancer survivors: a randomized controlled trial.

OBJECTIVES: Cancer survivors often report cognitive problems. Furthermore, decreases in physical activity typically occur over the course of cancer treatment. Although physical activity benefits cognitive function in noncancer populations, evidence linking physical activity to cognitive function in cancer survivors is limited. In our recent randomized controlled trial, breast cancer survivors who received a yoga intervention had lower fatigue and inflammation following the trial compared with a wait list control group. This secondary analysis of the parent trial addressed yoga's impact on cognitive complaints. METHODS: Posttreatment stage 0-IIIA breast cancer survivors (n = 200) were randomized to a 12-week, twice-weekly Hatha yoga intervention or a wait list control group. Participants reported cognitive complaints using the Breast Cancer Prevention Trial Cognitive Problems Scale at baseline, immediately postintervention, and 3-month follow-up. RESULTS: Cognitive complaints did not differ significantly between groups immediately postintervention (p = 0.250). However, at 3-month follow-up, yoga participants' Breast Cancer Prevention Trial Cognitive Problems Scale scores were an average of 23% lower than wait list participants' scores (p = 0.003). These group differences in cognitive complaints remained after controlling for psychological distress, fatigue, and sleep quality. Consistent with the primary results, those who practiced yoga more frequently reported significantly fewer cognitive problems at 3-month follow-up than those who practiced less frequently (p < 0.001). CONCLUSIONS: These findings suggest that yoga can effectively reduce breast cancer survivors' cognitive complaints and prompt further research on mind-body and physical activity interventions for improving cancer-related cognitive problems.

Omega-3 supplementation and loneliness-related memory problems: secondary analyses of a randomized controlled trial.

OBJECTIVE: Loneliness enhances risk for episodic memory declines over time. Omega-3 supplementation can improve cognitive function for people experiencing mild cognitive difficulties. Accordingly, we explored whether omega-3 supplementation would attenuate loneliness-related episodic memory problems. METHODS: Participants (n = 138) from a parent randomized controlled trial were randomized to the placebo, 1.25 grams/d of omega-3, or 2.50 grams/d of omega-3 conditions for a 4-month period. They completed a baseline loneliness questionnaire and a battery of cognitive tests both at baseline and at the end of the randomized controlled trial. RESULTS: After adjustment for baseline verbal episodic memory scores, lonelier people within the placebo condition had poorer verbal episodic memory postsupplementation, as measured by immediate (b = -0.28, t (117) = -2.62, p = .010) and long-delay (b = -0.06, t (116) = -2.07, p = .040) free recall, than their less lonely counterparts. This effect was not observed in the 1.25- and 2.50-grams/d supplementation groups (all p values > .10). The plasma omega-6:omega-3 ratio data mirrored these results. There were no loneliness-related effects of omega-3 supplementation on short-delay recall or the other cognitive tests (all p values > .32). CONCLUSION: These results suggest that omega-3 supplementation attenuates loneliness-related verbal episodic memory declines over time and support the use of exploring novel interventions for treating episodic memory problems among lonely people. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00385723.

Lower subjective social status exaggerates interleukin-6 responses to a laboratory stressor.

Growing evidence suggests that lower subjective social status (SSS), which reflects where a person positions himself on a social ladder in relation to others, is independently related to poor health. People who rate themselves lower in status also experience more frequent stressors and report higher stress than those who rate themselves higher in status, and chronic stress can enhance an individual's response to subsequent stressors. To address whether SSS predicted stress-induced interleukin-6 (IL-6) changes, we assessed 138 healthy adults at rest and following the Trier Social Stress Test (TSST). Participants completed the TSST at two study visits, separated by 4 months. People who placed themselves lower on the social ladder had larger IL-6 responses from baseline to 45 min post-stressor (p=0.01) and from baseline to 2h post-stressor (p=0.03) than those who placed themselves higher on the social ladder. Based on a ratio of subjective threat and coping ratings of the stress task, participants who viewed themselves as lower in status also tended to rate the speech task as more threatening and less manageable than those who viewed themselves as higher in status (p=0.05). These data suggest that people with lower perceived status experience greater physiological and psychological burden from brief stressors compared to those with higher perceived status. Accordingly, responses to stressors may be a possible mechanistic link among SSS, stress, and health.

Relationships and Inflammation across the Lifespan: Social Developmental Pathways to Disease.

There are well documented links between close relationships and physical health, such that those who have supportive close relationships have lower rates of morbidity and mortality compared to those who do not. Inflammation is one mechanism that may help to explain this link. Chronically high levels of inflammation predict disease. Across the lifespan, people who have supportive close relationships have lower levels of systemic inflammation compared to people who have cold, unsupportive, conflict-ridden relationships. Not only are current relationships associated with inflammation, but past relationships are as well. In this article, we will first review the literature linking current close relationships across the lifespan to inflammation. We will then explore recent work showing troubled past relationships also have lasting consequence on people's inflammatory levels. Finally, we will explore developmental pathways that may explain these findings.