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  1. All, Over on the loneliness thread we've discussed how loneliness (or perhaps even simply living alone) can increase mortality (PMID 21834390). And as Zeta pointed out in this post about this article, loneliness can aggravate chronic viral infections, which in turn are associated with more rapid cognitive decline, as discussed in this post about PMID 26710257. So besides practicing CR, which at least in some of us seems to promote psychological resilience and a sense of "calm abiding", what can we do to avoid the apparent negative effects (esp. inflammation) resulting from loneliness, and stress/anxiety in general? This new study [1] (popular press article) from CMU1 researchers, and some of the papers it cites (see below) suggest a solution, namely mindfulness meditation, a practice I find quite helpful, as discussed here. Study [1] was a randomized control trial comparing the effects of 3-days of mindfulness training vs. relaxation training in 35 stressed and unemployed job seekers. Using FMRI brain imaging, they found that mindfulness training (vs. relaxation training) positively influenced activity in both the default mode network (the network of areas in the brain that becomes active when we aren't engaged in deliberate thought - e.g. when ruminating) and in the left dorsolateral prefrontal cortex, a brain area involved in executive function. But most importantly for this topic, they found that four months after the intervention, those in the mindfulness meditation group had reduced levels of an important marker of inflammation, interleukin-6, relative to the relaxation training group. This effect was independent of whether during the intervening 4 months the subjects found a job or not, which half of the subjects in each group in fact did. Some of the interesting commentary on the research expressed by the authors in the popular press article : The researchers concluded that the changes in functional brain connectivity resulting from the mindfulness program seemed to help the brain manage stress (a known inflammation trigger), and therefore is responsible for the reduced levels of inflammation. Why does it seem to be more beneficial than mere relaxation for managing stress? [Lead researcher] Creswell suggests that mindfulness may have a more lasting impact. "Mindfulness meditation teaches participants how to be more open and attentive to their experiences, even difficult ones," Creswell said. "By contrast, relaxation approaches are good in the moment for making the body feel relaxed, but ... [they're] harder to translate when you are dealing with difficult stressors in your daily life." In the full text of the paper, the authors point to a number of other recent studies [2-5] that have found mindfulness meditation reduces both stress and inflammatory markers in the elderly, people experiencing job stress, as well as cancer patients and caregivers. Study [2] by this same group of researchers is particularly germane for this topic, since it investigated the effects of mindfulness meditation on feelings of loneliness and inflammation in elderly subjects. People who did 8 weeks of once-per-week mindfulness classes reported reduced loneliness and exhibited a decrease in pro-inflammatory gene expression relative to a control group from the waiting list for the mindfulness training. I resonated with this quote from the introduction of [2]: “Usually we regard loneliness as an enemy. Heartache is not something we choose to invite in. It's restless and pregnant and hot with the desire to escape and find something or someone to keep us company. When we can rest in the middle [through meditation practice], we begin to have a nonthreatening relationship with loneliness, a relaxing and cooling loneliness that completely turns our usual fearful patterns upside down” -- Pema Chodron (2000), Buddhist nun and teacher These were small studies and not without some shortcomings - e.g. the mindfulness training classes themselves might have reduced loneliness in [2]. But they are nonetheless suggestive evidence that practicing mindfulness meditation can help one deal with the negative effects of loneliness and stress in general. --Dean ----------- 1CMU is my alma mater and is located in Pittsburgh. Those Pittsburgh scientists are really churning out interesting research! -------------- [1] Biological Psychiatry, http://dx.doi.org/10.1016/j.biopsych.2016.01.008 Alterations in resting state functional connectivity link mindfulness meditation with reduced interleukin-6: a randomized controlled trial, J. David Creswell PhD, Adrienne A. Taren MD, Emily K. Lindsay MA, Carol M. Greco PhD, Peter J. Gianaros PhD, April Fairgrieve BS, Anna L. Marsland PhD, Kirk Warren Brown PhD, Baldwin M. Way PhD, Rhonda K. Rosen LCSW, Jennifer L. Ferris MA Full text: http://dx.doi.org.sci-hub.io/10.1016/j.biopsych.2016.01.008 Abstract Background Mindfulness meditation training interventions have been shown to improve markers of health, but the underlying neurobiological mechanisms are not known. Building on initial cross-sectional research showing that mindfulness meditation may increase default mode network (DMN) resting state functional connectivity (rsFC) with regions important in top-down executive control (dorsolateral prefrontal cortex, dlPFC), here we test whether mindfulness meditation training increases DMN-dlPFC rsFC, and whether these rsFC alterations prospectively explain improvements in interleukin-6 (IL-6) in a randomized controlled trial. Method Stressed job-seeking unemployed community adults (N=35) were randomized to either a 3-day intensive residential mindfulness meditation or relaxation training program. Participants completed a five-minute resting state scan before and after the intervention program. Participants also provided blood samples at pre-intervention and at 4-month follow-up, which were assayed for circulating IL-6, a biomarker of systemic inflammation. Results We tested for alterations in DMN rsFC using a posterior cingulate cortex (PCC) seed-based analysis, and found that mindfulness meditation training, and not relaxation training, increased PCC rsFC with left dlPFC (p<.05, corrected). These pre-post training alterations in PCC-dlPFC rsFC statistically mediated mindfulness meditation training improvements in IL-6 at 4-month follow-up. Specifically, these alterations in rsFC statistically explained 30% of the overall mindfulness meditation training effects on IL-6 at follow-up. Conclusions These findings provide the first evidence that mindfulness meditation training functionally couples the DMN with a region known to be important in top-down executive control at rest (left dlPFC), which in turn is associated with improvements in a marker of inflammatory disease risk. Trial Registration The RCT is registered on clinicaltrials.gov (#NCT01628809) Key words: mindfulness meditation, functional connectivity, IL-6, unemployment, fMRI, stress ---------------- [2] Brain Behav Immun. 2012 Oct;26(7):1095-101. doi: 10.1016/j.bbi.2012.07.006. Epub 2012 Jul 20. Mindfulness-Based Stress Reduction training reduces loneliness and pro-inflammatory gene expression in older adults: a small randomized controlled trial. Creswell JD1, Irwin MR, Burklund LJ, Lieberman MD, Arevalo JM, Ma J, Breen EC, Cole SW. Free full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3635809/ Abstract Lonely older adults have increased expression of pro-inflammatory genes as well as increased risk for morbidity and mortality. Previous behavioral treatments have attempted to reduce loneliness and its concomitant health risks, but have had limited success. The present study tested whether the 8-week Mindfulness-Based Stress Reduction (MBSR) program (compared to a Wait-List control group) reduces loneliness and downregulates loneliness-related pro-inflammatory gene expression in older adults (N = 40). Consistent with study predictions, mixed effect linear models indicated that the MBSR program reduced loneliness, compared to small increases in loneliness in the control group (treatment condition × time interaction: F(1,35) = 7.86, p = .008). Moreover, at baseline, there was an association between reported loneliness and upregulated pro-inflammatory NF-κB-related gene expression in circulating leukocytes, and MBSR downregulated this NF-κB-associated gene expression profile at post-treatment. Finally, there was a trend for MBSR to reduce C Reactive Protein (treatment condition × time interaction: (F(1,33) = 3.39, p = .075). This work provides an initial indication that MBSR may be a novel treatment approach for reducing loneliness and related pro-inflammatory gene expression in older adults. PMID: 22820409 ---------- [3] Malarkey WB, Jarjoura D, Klatt M (2013): Workplace based mindfulness practice and inflammation: A randomized trial. Brain Behav Immun. 27: 145–154. --------- [4] Rosenkranz MA, Davidson RJ, MacCoon DG, Sheridan JF, Kalin NH, Lutz A (2013): A comparison of mindfulness-based stress reduction and an active control in modulation of neurogenic inflammation. Brain Behav Immun. 27C: 174–184. -------------- [5] Lengacher CA, Kip KE, Barta MK, Post-White J, Jacobsen P, Groer M, et al. (2012): A Pilot Study Evaluating the Effect of Mindfulness-Based Stress Reduction on Psychological Status, Physical Status, Salivary Cortisol, and Interleukin-6 Among Advanced-Stage Cancer Patients and Their Caregivers. J Holist Nurs. 30: 170–185.
  2. Dean Pomerleau

    CR May Make Your Kids Chill Out

    I thought this new study [1] that James Cain posted in his great weekly CR research update (thanks James!) was well worth promoting to its own post/thread. And without a little digging & careful reading, it wasn't clear to me what it was saying. So here is my interpretation. These researchers subjected adult male rats to 25% CR prior to breeding them. They then raised the male offspring of these CR'ed rats to adulthood, and subjected them to a battery of tests to measure their anxiety-related behavior. What they found across a variety of metrics was that the male offspring of CR'ed rats were less anxious than the male offspring of rats fed ad lib. One test where the offspring of CR'ed rats weren't less anxious / cautious was the alarm they exhibited when exposed to signs of a predator (cat urine). So in a sense, the offspring of CR'ed rodents were more mellow, but no less sensitive to real danger. Overall, it seemed like a good result to me, and one that I wouldn't have necessarily expected. My intuition would say that hardship of CR in dad might make his kids more neurotic, rather than less. The authors suggest the influence of CR in one generation on the psychological tendencies of offspring in the following generation is potentially mediated epigenetically. To me it seems hard to imagine how it would happen otherwise, since I don't believe the male parent rats were involved in the rearing of their offspring in this study (i.e. it was a one-night-stand with mom after which the dads were out of the kids' life). So this study did not address the influence of practicing CR in the presence of children on the children's psychological health, attitude towards food, etc. I think that would be at least as interesting a topic to investigate. --Dean ------------- [1] Psychoneuroendocrinology. 2015 Oct 30;64:1-11. doi: 10.1016/j.psyneuen.2015.10.020. [Epub ahead of print] Paternal calorie restriction prior to conception alters anxiety-like behavior of the adult rat progeny. Govic A(1), Penman J(2), Tammer AH(3), Paolini AG(4). The maternal environment influences a broad range of phenotypic outcomes for offspring, with anxiety-like behavior being particularly susceptible to maternal environmental perturbations. Much less is known regarding paternal environmental influences. To investigate this, adult male rats were exposed to 25% calorie restriction (CR) or glucocorticoid elevation (CORT; 200μg/ml of corticosterone in drinking water) for ∼6 weeks prior to breeding. Elevated plus maze (EPM), open field (OF), predator odor (cat urine), and acoustic startle/pre-pulse inhibition (AS/PPI) were characterised in the adult male offspring. Plasma concentrations of corticotrophin-releasing hormone (CRF), adrenocorticotropin hormone (ACTH), and serum lepin were characterised in both sires and offspring. Maternal care received by litters was additionally observed. Expectedly, CR and CORT treatment attenuated weight gain, whilst only CR induced anxiolytic behavior in the EPM. The adult offspring sired by CR males also demonstrated a reduction in weight gain, food intake and serum leptin levels when compared to controls. Moreover, CR offspring demonstrated an anxiolytic-like profile in the EPM and OF, enhanced habituation to the AS pulse, reduced PPI, but no alteration to predator odor induced defensiveness compared to control. CORT offspring failed to demonstrate any behavioral differences from controls, however, exhibited a trend towards reduced ACTH and leptin concentration. Collectively, the results indicate that a reduction in calories in males prior to conception can affect the behavior of adult offspring. The phenotypic transmission of CR experiences from fathers to the progeny could potentially be mediated epigenetically. The role of glucocorticoid elevation and maternal care are also discussed. Copyright © 2015 Elsevier Ltd. All rights reserved. PMID: 26571216