14 research outputs found
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Lipopolysaccharide-stimulated intracellular cytokines and depressive symptoms in community-dwelling older adults
BackgroundInflammation is involved in the pathophysiology of depression, and circulating inflammatory cytokines have been associated with depressive symptoms. However, measuring circulating cytokines have inherent methodological limitations. In vitro lipopolysaccharide (LPS)-stimulated intracellular cytokines (ICCs) overcome these limitations. Furthermore, because psychosocial and physiological stressors activate inflammatory responses and LPS-stimulated ICCs reflect the inflammatory responsivity of monocytes to such stressors, ICCs may reflect individual stress responsivity.MethodsThis cross-sectional study examined whether LPS-stimulated expression of ICCs in peripheral blood mononuclear cells (PBMCs) is a sensitive inflammation measure correlated with depressive symptoms in 180 community-dwelling older adults. We tested correlations of not only intracellular but also circulating inflammatory markers with depressive symptoms assessed using the 10-item Center for Epidemiological Studies Depression Scale (CES-D). Intracellular markers included expression of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and both in PBMCs. Circulating markers included IL-6, TNF-α, and C-reactive protein (CRP) in plasma.ResultsNone of the correlations were statistically significant. However, in contrast to circulating markers, the correlations of ICCs were consistently in the expected direction, i.e., higher ICC expression correlating with higher depression severity.DiscussionDespite the non-significant findings, further research is required for the evaluation of LPS-stimulated ICC expression as biomarkers of depressive symptoms
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Transcriptomic predictors of inflammation-induced depressed mood.
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
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Associations of objective versus subjective social isolation with sleep disturbance, depression, and fatigue in community-dwelling older adults.
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
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Kynurenine metabolism and inflammation-induced depressed mood: A human experimental study.
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
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Prevalence and Predictors of Sleep-Disordered Breathing in Men Participating in the Multicenter AIDS Cohort Study
Data on the prevalence of sleep-disordered breathing (SDB) in people with HIV are limited. Moreover, whether the associations between SDB and age or BMI differ by HIV status is unknown.
Is SDB more prevalent in men with HIV than those without HIV, and do the predictors of SDB differ between the two groups?
Home polysomnography was used in the Multicenter AIDS Cohort Study to assess SDB prevalence in men with (n = 466; 92% virologically suppressed) and without (n = 370) HIV. SDB was defined using the oxygen desaturation index (ODI) and the apnea-hypopnea index (AHI), using four definitions: ≥ 5 events/h based on an ODI with a 3% (ODI3) or 4% (ODI4) oxygen desaturation, or an AHI with a 3% oxygen desaturation or EEG arousal (AHI3a) or with a 4% oxygen desaturation (AHI4).
SDB prevalence was similar in men with and without HIV using the ODI3 and AHI3a definitions. However, SDB prevalence was higher in men with than without HIV using the ODI4 (55.9% vs 47.8%; P = .04) and the AHI4 definitions (57.9% vs 50.4%; P = .06). Mild and moderate SDB were more common in men with than without HIV. Associations between SDB prevalence and age, race, and BMI were similar in men with and without HIV. Among men with HIV, viral load, CD4 cell count, and use of antiretroviral medications were not associated with SDB prevalence.
SDB prevalence was high overall but greater in men with than without HIV using the ODI4 threshold definition. Efforts to diagnose SDB are warranted in people with HIV, given that SDB is associated with daytime sleepiness and impaired quality of life.
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Shorter total sleep time is associated with lower CD4+/CD8+ T cell ratios in virally suppressed men with HIV
Abstract Study Objectives Although poor sleep quality is associated with lower CD4+ T cell counts among people living with HIV (PLWH), the association between objective sleep metrics and T lymphocyte subset counts is unknown. We evaluated the association between polysomnography (PSG) derived sleep metrics and T lymphocyte subpopulations in a cohort of men living with HIV. Methods Virally suppressed men living with HIV participating in the Multicenter AIDS Cohort Study underwent home overnight PSG. We assessed the association of PSG parameters with CD4+ and CD8+ T cell counts and the CD4+/CD8+ T cell ratio. Results Overall, 289 men with mean (±SD) age 55.3 ±11.3 years and mean CD4+ T cell count 730 ±308 cells/mm3 were evaluated. Total sleep time (TST) was significantly associated with CD8+ but not CD4+ T cell counts. After adjusting for age, race, depressive symptoms, antidepressant use, and non-nucleoside reverse transcriptase inhibitors use, every hour of shorter TST was associated with an additional 33 circulating CD8+ T cells/mm3 (p=0.05) and a 5.6% (p=0.0007) decline in CD4+/CD8+ T cell ratio. In adjusted models, every hour of shorter REM sleep was associated with an additional 113 CD8+ T cells/mm3 (p=0.02) and a 15.1% lower CD4+/CD8+ T cell ratio (p=0.006). In contrast, measures of sleep efficiency and sleep-disordered breathing were not associated with differences in T lymphocyte subpopulations. Conclusions Our findings suggest that shorter TST and REM sleep durations are associated with differences in T lymphocyte subpopulations among men living with HIV. Addressing sleep may reflect a novel opportunity to improve immune function in PLWH
Methods for home-based self-applied polysomnography: the Multicenter AIDS Cohort Study
Abstract
Study Objectives
Along with multiple chronic comorbidities, sleep disorders are prevalent in people living with human immunodeficiency virus (HIV) infection. The goal of this study was to establish methods for assessing sleep quality and breathing-related disorders using self-applied home polysomnography in people with and without HIV.
Methods
Self-applied polysomnography was conducted on 960 participants in the Multicenter AIDS Cohort Study (MACS) using the Nox A1 recorder to collect data on the frontal electroencephalogram (EEG), bilateral electrooculograms, and a frontalis electromyogram during sleep. Breathing patterns were characterized using respiratory inductance plethysmography bands and pulse oximetry. Continuous recordings of the electrocardiogram were also obtained. All studies were scored centrally for sleep stages and disordered breathing events.
Results
Successful home polysomnography was obtained in 807 of 960 participants on the first attempt and 44 participants on the second. Thus, a successful polysomnogram was obtained in 851 (88.6%) of the participants. Reasons for an unsuccessful study included less than 3 h of data on oximetry (34.6%), EEG (28.4%), respiratory inductance plethysmography (21.0%), or two or more of these combined (16.0%). Of the successful studies (N = 851), signal quality was rated as good, very good, or excellent in 810 (95.2%). No temporal trends in study quality were noted. Independent correlates of an unsuccessful study included black race, current smoking, and cocaine use.
Conclusions
Home polysomnography was successfully completed in the MACS demonstrating its feasibility in a community cohort. Given the burden of in-lab polysomnography, the methods described herein provide a cost-effective alternative for collecting sleep data in the home