Research in human social genomics has identified a conserved transcriptional response to adversity (CTRA) characterized by up-regulated expression of pro-inflammatory genes and down-regulated ...expression of Type I interferon- and antibody-related genes. This report seeks to identify the specific aspects of positive psychological well-being that oppose such effects and predict reduced CTRA gene expression. In a new confirmation study of 122 healthy adults that replicated the approach of a previously reported discovery study, mixed effect linear model analyses identified a significant inverse association between expression of CTRA indicator genes and a summary measure of eudaimonic well-being from the Mental Health Continuum - Short Form. Analyses of a 2- representation of eudaimonia converged in finding correlated psychological and social subdomains of eudaimonic well-being to be the primary carriers of CTRA associations. Hedonic well-being showed no consistent CTRA association independent of eudaimonic well-being, and summary measures integrating hedonic and eudaimonic well-being showed less stable CTRA associations than did focal measures of eudaimonia (psychological and social well-being). Similar results emerged from analyses of pooled discovery and confirmation samples (n = 198). Similar results also emerged from analyses of a second new generalization study of 107 healthy adults that included the more detailed Ryff Scales of Psychological Well-being and found this more robust measure of eudaimonic well-being to also associate with reduced CTRA gene expression. Five of the 6 major sub-domains of psychological well-being predicted reduced CTRA gene expression when analyzed separately, and 3 remained distinctively prognostic in mutually adjusted analyses. All associations were independent of demographic characteristics, health-related confounders, and RNA indicators of leukocyte subset distribution. These results identify specific sub-dimensions of eudaimonic well-being as promising targets for future interventions to mitigate CTRA gene expression, and provide no support for any independent favorable contribution from hedonic well-being.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
functional genomic perspective on human well-being Fredrickson, Barbara L.; Grewen, Karen M.; Coffey, Kimberly A. ...
Proceedings of the National Academy of Sciences - PNAS,
08/2013, Letnik:
110, Številka:
33
Journal Article
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To identify molecular mechanisms underlying the prospective health advantages associated with psychological well-being, we analyzed leukocyte basal gene expression profiles in 80 healthy adults who ...were assessed for hedonic and eudaimonic well-being, as well as potentially confounded negative psychological and behavioral factors. Hedonic and eudaimonic well-being showed similar affective correlates but highly divergent transcriptome profiles. Peripheral blood mononuclear cells from people with high levels of hedonic well-being showed up-regulated expression of a stress-related conserved transcriptional response to adversity (CTRA) involving increased expression of proinflammatory genes and decreased expression of genes involved in antibody synthesis and type I IFN response. In contrast, high levels of eudaimonic well-being were associated with CTRA down-regulation. Promoter-based bioinformatics implicated distinct patterns of transcription factor activity in structuring the observed differences in gene expression associated with eudaimonic well-being (reduced NF-κB and AP-1 signaling and increased IRF and STAT signaling). Transcript origin analysis identified monocytes, plasmacytoid dendritic cells, and B lymphocytes as primary cellular mediators of these dynamics. The finding that hedonic and eudaimonic well-being engage distinct gene regulatory programs despite their similar effects on total well-being and depressive symptoms implies that the human genome may be more sensitive to qualitative variations in well-being than are our conscious affective experiences.
The purpose of this study was to uncover the day-to-day emotional profiles and dose-response relations, both within persons and between persons, associated with initiating one of two meditation ...practices, either mindfulness meditation or loving-kindness meditation. Data were pooled across two studies of midlife adults (
N
= 339) who were randomized to learn either mindfulness meditation or loving-kindness meditation in a 6-week workshop. The duration and frequency of meditation practice was measured daily for 9 weeks, commencing with the first workshop session. Likewise, positive and negative emotions were also measured daily, using the modified Differential Emotions Scale (Fredrickson,
Advances in Experimental Social Psychology
47:1–53,
2013
). Analysis of daily emotion reports over the targeted 9-week period showed significant gains in positive emotions and no change in negative emotions, regardless of meditation type. Multilevel models also revealed significant dose-response relations between duration of meditation practice and positive emotions, both within persons and between persons. Moreover, the within-person dose-response relation was stronger for loving-kindness meditation than for mindfulness meditation. Similar dose-response relations were observed for the frequency of meditation practice. In the context of prior research on the mental and physical health benefits produced by subtle increases in day-to-day experiences of positive emotions, the present research points to evidence-based practices—both mindfulness meditation and loving-kindness meditation—that can improve emotional well-being.
Tumor necrosis factor inhibitors, including infliximab and adalimumab, are a mainstay of pediatric Crohn’s disease therapy; however, nonresponse and loss of response are common. As combination ...therapy with methotrexate may improve response, we performed a multicenter, randomized, double-blind, placebo-controlled pragmatic trial to compare tumor necrosis factor inhibitors with oral methotrexate to tumor necrosis factor inhibitor monotherapy.
Patients with pediatric Crohn’s disease initiating infliximab or adalimumab were randomized in 1:1 allocation to methotrexate or placebo and followed for 12–36 months. The primary outcome was a composite indicator of treatment failure. Secondary outcomes included anti-drug antibodies and patient-reported outcomes of pain interference and fatigue. Adverse events (AEs) and serious AEs (SAEs) were collected.
Of 297 participants (mean age, 13.9 years, 35% were female), 156 were assigned to methotrexate (110 infliximab initiators and 46 adalimumab initiators) and 141 to placebo (102 infliximab initiators and 39 adalimumab initiators). In the overall population, time to treatment failure did not differ by study arm (hazard ratio, 0.69; 95% CI, 0.45–1.05). Among infliximab initiators, there were no differences between combination and monotherapy (hazard ratio, 0.93; 95% CI, 0.55–1.56). Among adalimumab initiators, combination therapy was associated with longer time to treatment failure (hazard ratio, 0.40; 95% CI, 0.19–0.81). A trend toward lower anti-drug antibody development in the combination therapy arm was not significant (infliximab: odds ratio, 0.72; 95% CI, 0.49–1.07; adalimumab: odds ratio, 0.71; 95% CI, 0.24–2.07). No differences in patient-reported outcomes were observed. Combination therapy resulted in more AEs but fewer SAEs.
Among adalimumab but not infliximab initiators, patients with pediatric Crohn’s disease treated with methotrexate combination therapy experienced a 2-fold reduction in treatment failure with a tolerable safety profile. ClinicalTrials.gov, Number: NCT02772965.
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Tumor necrosis factor inhibitors, including infliximab and adalimumab, are a mainstay of pediatric Crohn’s disease therapy; however, nonresponse and loss of response is common. Combination therapy with methotrexate may improve response. This randomized clinical trial compared tumor necrosis factor inhibitor combination therapy with methotrexate to tumor necrosis factor inhibitor alone. Combination therapy outperformed monotherapy for patients starting adalimumab, but not infliximab.
Disparities in the recruitment of minority populations in research are well-documented. However, the degree of participation and retention of minorities following enrollment is less known, ...particularly in decentralized studies. Although decentralized clinical research methods may allow researchers to engage broader study populations with less participation burden, they may present different retention challenges. To evaluate racial and ethnic differences in the degree of participation after enrollment in a decentralized study, we analyzed data from a cohort of patients with inflammatory bowel diseases following COVID-19 immunization.
We compared by race and ethnicity the following post-enrollment participation metrics: response to > 50% of follow-up surveys, donation of a blood sample for antibody testing, consent to use of bio samples for future research, and withdrawal prior to study completion.
Overall, we observed higher levels of post-enrollment study participation among non-Hispanic White (NHW) participants as compared to Black or Hispanic participants: 95% of NHW participants completed follow-up versus 87% of Black participants and 91% of Hispanic participants, 73% of NHW participants provided bio samples versus 64% Black participants and 67% Hispanic participants, and 65% of NHW participants provided consent for future research versus 62% of Black participants and 52% of Hispanic participants.
Our findings demonstrate that the degree of study participation after enrollment in this decentralized study differed by race and ethnicity, indicating that attention to diversity, equity, and inclusion is needed not only in clinical research recruitment but also throughout study administration.
Obesity is common among patients with pediatric Crohn's disease (PCD). Some adult studies suggest obese patients respond less well to anti-tumor necrosis factor (TNF) treatment. This study sought ...compares anti-TNF response and anti-TNF levels between pediatric patients with normal and high body mass index (BMI).
The COMBINE trial compared anti-TNF monotherapy with combination therapy with methotrexate in patients with PCD. In this secondary analysis, a comparison of time-to-treatment failure among patients with normal BMI vs BMI Z -score >1, adjusting for prescribed anti-TNF (infliximab IFX or adalimumab ADA), trial treatment assignment (combination vs monotherapy), and relevant covariates. Median anti-TNF levels across BMI category was also examined.
Of 224 participants (162 IFX initiators and 62 ADA initiators), 111 (81%) had a normal BMI and 43 (19%) had a high BMI. High BMI was associated with treatment failure among ADA initiators (7/10 70% vs 12/52 23%, hazard ratio 0.29, P = 0.007) but not IFX initiators. In addition, ADA-treated patients with a high BMI had lower ADA levels compared with those with normal BMI (median 5.8 vs 12.8 μg/mL, P = 0.02). IFX trough levels did not differ between BMI groups.
Overweight and obese patients with PCD are more likely to experience ADA treatment failure than those with normal BMI. Higher BMI was associated with lower drug trough levels. Standard ADA dosing may be insufficient for overweight children with PCD. Among IFX initiators, there was no observed difference in clinical outcomes or drug levels, perhaps due to weight-based dosing and/or greater use of proactive drug monitoring.
Objectives
In contrast to formal meditation, which involves setting aside other activities to engage in contemplative practice, informal meditation can happen at any moment within the flow of daily ...activities. Whether informal meditation practice improves well-being is unclear. The purpose of this investigation was to test hypotheses about the day-to-day socioemotional profiles and dose–response relations, both within persons and between persons, associated with informal meditation practice.
Methods
Midlife adults (
N
= 231), new to meditation, were randomized to learn either mindfulness meditation or loving–kindness meditation in a 6-week workshop that taught both formal and informal meditation practices. The frequency of informal meditation practice was measured daily for 9 weeks. Likewise, formal meditation, emotions, and perceptions of social integration were also measured daily.
Results
Multilevel models of daily reports over a 9-week period revealed significant dose–response relations between the frequency of informal meditation and positive emotions and perceived social integration—both within persons and between persons (positive emotions: within-person
b
= 0.05, 95% CI 0.03, 0.07, between-person
b
= 0.35, 95% CI 0.20, 0.51; social integration: within-person
b
= 0.11, 95% CI 0.07, 0.14, between-person
b
= 0.41, 95% CI 0.12, 0.70). Effects were comparable for the distinct informal practices of mindfulness and loving–kindness, and were statistically independent of the effects of formal meditation practice.
Conclusions
The present research demonstrated that, distinct from formal meditation practice, informal meditation practice is linked to both positive emotions and social integration in a dose–response manner.
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