Objective: Older adults are at higher risk of experiencing social isolation, which has been linked to impaired physical and mental health. The link between social isolation and health might be due to ...objective deprivation of social network and/or subjective experience of loneliness. This community-based cross-sectional study examined whether the associations between social isolation and behavioral symptoms including sleep disturbance, depression, and fatigue are mostly explained by its subjective component.
Methods: Randomly selected 2541 community-dwelling individuals in Los Angeles aged ≥60 years were telephone-interviewed regarding their objective and subjective social isolation (respectively social network size and loneliness), sleep disturbance, depression, and fatigue.
Results: When objective and subjective social isolation were separately included in multivariate regression models, both were significantly associated with behavioral symptoms. However, once they were simultaneously included in the same multivariate models, while subjective social isolation remained strongly associated (adjusted beta 0.24 for sleep disturbance P < 0.001, 0.44 for depression P < 0.001, 0.17 for fatigue P < 0.001), objective social isolation was weakly or non-significantly associated (-0.04 for sleep disturbance P = 0.03, -0.01 for depression P = 0.48, -0.003 for fatigue P = 0.89). Additionally, those with objective social isolation were found to have worse symptoms mostly when they also experienced subjective social isolation.
Conclusions: Older adults with objective social isolation may experience sleep disturbance, depression, and fatigue because they feel socially isolated, not just because they are deprived of social networks. Interventions that target social isolation might serve as potential treatments for improving behavioral health of older adults, especially by targeting its subjective component.
Inflammation plays a significant role in the pathophysiology of depression. However, not all individuals exposed to inflammatory challenge develop depression, and identifying those at risk is ...necessary to develop targeted monitoring, prevention, and treatment strategies. Within a randomized double-blind placebo-controlled study (n = 115), we examined whether leukocyte transcriptome profiles predicted inflammation-induced depressed mood in volunteers who received low-dose intravenous endotoxin (n = 58; aged 18-50). At baseline, transcription factor (TF) activities were assessed using genome-wide transcriptional profiling of peripheral blood mononuclear cells and promoter-based bioinformatic analyses. Then, participants were administered endotoxin. Self-reported depressed mood was assessed using the Profile of Mood States. Based on extant studies linking transcriptional profiles to depressive disorder, we examined whether post-endotoxin depressed mood is predicted by baseline activity of TFs related to immune activation, sympathetic activation, and glucocorticoid insensitivity: respectively, nuclear factor kappa B (NF-kB), cAMP response element-binding protein (CREB), and glucocorticoid receptor (GR). Twenty-one participants (36%) experienced an increase in depressed mood from baseline to 2 h post endotoxin, when depressive response peaks. Bioinformatics analyses controlling for age, sex, ethnicity, body mass index, and physical sickness response revealed that post-endotoxin depressed mood was predicted by increased baseline activity of TFs related to inflammation (NF-kB) and beta-adrenergic signaling (CREB) and by decreased activity of GR-related TFs (P's < 0.001). Inflammation-induced depressed mood is predicted by peripheral transcriptome profiles related to immune activation, sympathetic activation, and glucocorticoid insensitivity. With further replication, these stress-related molecular profiles could be used for a novel genomic approach for identifying individuals at high-risk for the inflammatory subtype of depression.
Cognitive behavioral therapy for insomnia (CBT-I) is the universally recommended treatment of choice for insomnia disorder based on its safety and posttreatment durability of benefit. However, CBT-I ...does not help all patients achieve remission. The second most evidence-based treatment, hypnotic pharmacotherapy (PCT), does not resolve perpetuating factors of insomnia, resulting in potential waning of benefit and dependence. This article presents a rationale that supports consideration of hypnotic augmentation of CBT-I (COMB), along with a review of select randomized controlled trials relevant to clinical decision-making.
A prior depressive episode is thought to increase the risk of depression. However, among older adults with prior depression, it is unclear whether sleep disturbance predicts depression recurrence ...independent of other depressive symptoms.
A 2-year prospective cohort study was conducted with 351 community-dwelling older adults ages 60 years and older: 145 persons with a history of major or nonmajor depression in full remission and 206 without a prior history of depression or any mental illness. The participants were assessed at baseline, 6 weeks, 1 year, and 2 years for depressive episodes, depressive symptoms, sleep quality, and chronic medical disease.
Twenty-three subjects (16.9%) with prior depression developed depressive episodes during follow-up, compared to only one person in the group without prior mental illness (0.5%). Within the group with prior depression, depression recurrence was predicted by sleep disturbance, and this association was independent of other depressive symptoms, chronic medical disease, and antidepressant medication use.
This study is the first to demonstrate that sleep disturbance acts as an independent risk factor for depression recurrence in community-dwelling older adults. To identify older adults at risk for depression, a two-step strategy can be employed, which involves assessment of the presence of a prior depressive episode along with sleep disturbance.
•Experimental inflammatory challenge acutely increases plasma levels of kynurenine pathway measures in humans.•Changes in plasma kynurenine and quinolinic acid positively correlate with ...inflammation-induced depressed mood.•Kynurenine metabolism may be a pathway linking inflammation and depressed mood.
Inflammation has an important physiological influence on mood and behavior. Kynurenine metabolism is hypothesized to be a pathway linking inflammation and depressed mood, in part through the impact of kynurenine metabolites on glutamate neurotransmission in the central nervous system. This study evaluated whether the circulating concentrations of kynurenine and related compounds change acutely in response to an inflammatory challenge (endotoxin administration) in a human model of inflammation-induced depressed mood, and whether such metabolite changes relate to mood change. Adults (n = 115) were randomized to receive endotoxin or placebo. Mood (Profile of Mood States), plasma cytokine (interleukin-6, tumor necrosis factor-α) and metabolite (kynurenine, tryptophan, kynurenic acid, quinolinic acid) concentrations were repeatedly measured before the intervention, and at 2 and 6 h post-intervention. Linear mixed models were used to evaluate relationships between mood, kynurenine and related compounds, and cytokines. Kynurenine, kynurenic acid, and tryptophan (but not quinolinic acid) concentrations changed acutely (p’s all <0.001) in response to endotoxin as compared to placebo. Neither kynurenine, kynurenic acid nor tryptophan concentrations were correlated at baseline with cytokine concentrations, but all three were significantly correlated with cytokine concentrations over time in response to endotoxin. Quinolinic acid concentrations were not correlated with cytokine concentrations either before or following endotoxin treatment. In those who received endotoxin, kynurenine (p = 0.049) and quinolinic acid (p = 0.03) positively correlated with depressed mood, although these findings would not survive correction for multiple testing. Changes in tryptophan and kynurenine pathway metabolites did not mediate the relationship between cytokines and depressed mood. Further work is necessary to clarify the pathways leading from inflammation to depressed mood in humans.
Background Accumulating evidence suggests that sleep disturbance is associated with inflammation and related disorders including cardiovascular disease, arthritis, and diabetes mellitus. This study ...was undertaken to test the effects of sleep loss on activation of nuclear factor (NF)-κB, a transcription factor that serves a critical role in the inflammatory signaling cascade. Methods In 14 healthy adults (seven women; seven men), peripheral blood mononuclear cell NF-κB was repeatedly assessed, along with enumeration of lymphocyte subpopulations, in the morning after baseline sleep, partial sleep deprivation (awake from 11 pm to 3:00 am ), and recovery sleep. Results In the morning after a night of sleep loss, mononuclear cell NF-κB activation was significantly greater compared with morning levels following uninterrupted baseline or recovery sleep, in which the response was found in female but not in male subjects. Conclusions These results identify NF-κB activation as a molecular pathway by which sleep disturbance may influence leukocyte inflammatory gene expression and the risk of inflammation-related disease.
Abstract
Systemic inflammation is associated with increasing age. Yet, there are limited data about the association between age and systemic inflammation within older adults, and whether older age is ...also associated with cellular and nuclear signaling markers of inflammation. In community-dwelling older adults (N = 262, 60–88 years), systemic levels of C-reactive protein, interleukin-6, and soluble tumor necrosis factor receptor II; levels of toll-like receptor-4–stimulated monocytic production of interleukin-6 and tumor necrosis factor α; and resting nuclear levels of activated nuclear factor kappa B and signal transducer and activator of transcription (STAT1, STAT3, STAT5) were evaluated. Adjusting for demographic and clinical factors, multivariate linear regression tested the association between age and each inflammatory marker. Age was positively associated with increased levels of interleukin-6 and soluble tumor necrosis factor receptor II (p’s < .05) and with increases in STAT1, STAT3, and STAT5 activation (p’s < .05). However, no relationship was found between age and C-reactive protein, toll-like receptor-4–stimulated interleukin-6/tumor necrosis factor alpha α production, or nuclear factor kappa B. Within a community-dwelling sample of older adults, older age is associated with increases in STAT activation, along with increases of systemic inflammatory cytokines. In older adults, heterogeneity in age-related increases in inflammatory disease risk may be related to individual variability in inflammation.
This study was conducted to provide basic data for chemical accident response by assessing the health risks of residents living near a chemical accident site due to long-term exposure. The study ...considered the temporal concentration changes of the leaked chemical (i.e., its behavior in the environment and dilution) until its extinction. A virtual chemical accident was assumed, in which 40 t of formaldehyde was accidentally discharged for 1 h in Ulsan Metropolitan City, Korea. Formaldehyde concentrations over time in each environmental medium after the accident were calculated using a multimedia environmental dynamics model. Exposure subjects divided into four age groups were considered. Carcinogenic risks due to respiration and non-carcinogenic risks due to soil intake were assessed. For all the age groups, the excess cancer risk did not exceed 1.0 × 10
−6
, indicating that no harmful health impact was caused by inhalation exposure to formaldehyde. The hazard index exceeded 1 for all the age groups, confirming that harmful health impacts were caused by exposure to soil containing the formaldehyde. This study is the first to assess chronic health risks by reflecting long-term residual and temporal concentration changes of a pollutant released in a chemical accident in each environmental medium until its extinction. This work is also significant in that it reflects the exposure characteristics of the toxic chemical.
Abstract
Introduction
Low CD4+ T lymphocyte counts and CD4+/CD8+ lymphocyte ratios predict mortality and cardiovascular risk among people living with HIV (PLWH). Whether polysomnographic (PSG) sleep ...measures impact T lymphocyte subset counts among PLWH is unknown. We sought to evaluate the association between lymphocyte subsets and PSG-derived sleep measures in a cohort with HIV seropositive men.
Methods
We analyzed data from HIV seropositive men who have sex with men participating in the Multicenter AIDS Cohort Study on antiretroviral therapy for >1 year with undetectable (<500 copies/mL) plasma HIV-1 RNA who underwent a sleep evaluation with home polysomnography. The following seven sleep parameters were examined: total sleep time (TST), sleep efficiency, sleep stage (N1, N2, N3, and REM) duration, and apnea-hypopnea index. Multivariable linear regression models adjusted for age and body mass index were used to assess whether sleep measures were associated with CD4+ T cell count, CD8+ T cell count, or CD4+/CD8+ ratio.
Results
Participants (n= 286) had a mean age of 55.2 ± 11.3 years, 52.8% had sleep apnea and mean CD4+ count was 728 ± 306 cells/mm3. None of the sleep measures were associated with CD4+ counts but longer TST and REM duration were associated with lower CD8+ counts and higher CD4+/CD8+ ratio. In adjusted analyses, every one hour increase in TST was associated with a 35 ± 18 cells/mm3 lower CD8+ count (p=0.049) and 6.3% elevation in CD4+/CD8+ ratio (p=0.006) while every hour increase in REM was associated with 123 ± 50 cells/mm3 lower CD8+ count (p=0.01) and 20% elevation in CD4+/CD8+ ratio (p=0.003).
Conclusion
In PLWH, longer total sleep time and REM sleep duration are associated with protective CD4+/CD8+ ratios due to lower CD8+ cell count. Further research is needed to assess if longer sleep duration is associated with decreased inflammatory markers.
Support (if any)
American Thoracic Society Academic Sleep Pulmonary Integrated Research/Clinical (ASPIRE) Fellowship
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