Reduced stress and inflammatory responsiveness in experienced meditators compared to a matched healthy control group
Introduction
Psychological stress is now widely accepted as an important trigger of inflammation and a major contributor to symptoms of chronic inflammatory disease (Pace et al., 2009, Rohleder, 2014, Steptoe et al., 2001, Weik et al., 2008). As such, the impact of behavioral interventions designed to reduce psychological stress, such as meditation training, on inflammatory outcomes has been a growing focus of interest and attention by the scientific community. The overwhelming majority of studies addressing this question have randomly assigned participants to relatively short interventions (Bower and Irwin, 2015, Gu et al., 2015, Khoury et al., 2015). While this design is considered the gold-standard and has considerable merit, it also has some shortcomings when applied to behavioral interventions, that may be reflected in the mixed results reported in the literature (Black et al., 2015, Malarkey et al., 2013, Morgan et al., 2014, Rosenkranz et al., 2013). First, the ability of these interventions to reliably reduce stress may be highly variable across individuals and/or of small effect size in the early stages of training, perhaps becoming more stable and more easily detectible when the trained skills become more established. Second, the efficacy of any behavioral intervention is predicated upon an individual’s engagement with the training and the persistence of practice, unlike in a pharmaceutical trial, where one can be fairly confident that every individual is receiving roughly the same dose. Outside of the laboratory, individuals choose pathways of change that they are most drawn to, or for which they have some aptitude. Choice is a strong predictor of adherence to and engagement in an intervention (Lindhiem et al., 2014, Rennie et al., 2007) and effect sizes have been shown to be higher when an intervention is individually initiated, rather than part of a volunteer effort (Brown et al., 2015). Thus, through random assignment, these studies may unintentionally reduce the effect size of the intervention. As a complement to the extant RCTs, the current study was designed to compare individuals with a long-standing and self-initiated practice of meditation to a carefully matched group of healthy, non-meditating community volunteers in stress- and inflammatory responsiveness.
Major advances have been made in the last decade in our understanding of the mechanisms that underlie the relationship between stress and inflammation. However, most of these advances have been focused on the impact of stress on brain-immune pathways that function systemically, whereas very little attention has been paid to pathways through which stress modulates inflammation locally. Though systemic elevations in inflammatory markers are not uncommon in individuals suffering from chronic inflammatory diseases, local inflammatory processes are often more sensitive indicators of disease onset and progression (Bamias et al., 2013, Lotti et al., 2014, Riol-Blanco et al., 2014, Schleich et al., 2014, Ugraş et al., 2011) and the two are not always highly correlated (Davel et al., 2012, Lima et al., 2015, Malinovschi et al., 2013, Schleich et al., 2014, Vernooy et al., 2002). For this reason, we chose capsaicin application to skin as our model to investigate stress responsiveness and local neurogenic inflammation in long-term meditators and community controls.
Capsaicin is a naturally occurring compound found in hot peppers that imparts their “hotness”. It causes depolarization of predominantly C-fiber type sensory neurons by binding to vanilloid receptors (sub-type 1; TRPV1), leading to a descending impulse or axon reflex. The axon reflex travels down branches of the same sensory nerve, causing neuropeptide release from nearby terminals. When these neuropeptides are released in the skin, they evoke a neurogenic inflammatory response, characterized by a “flare response” − the area of redness or erythema that extends beyond the area covered by capsaicin, which is caused by nerve-mediated vasodilation (Helme and McKernan, 1985, Holzer, 1988).
We hypothesized that long-term meditators (LTMs) would have a smaller physiological stress response to an acute laboratory stressor and a reduced flare response to capsaicin application. Further, we predicted that the reduction in stress response would account for a significant amount of variance in the size of the flare. Finally, we hypothesized that smaller stress hormone and flare responses would be associated with lower perceived stress and better mental and physical well-being.
Section snippets
Participants
Our participants included 37 meditation-naïve participants (MNP; average age 48.0 ± 10.4 years, 25 female) and 31 long-term meditators (LTM; average age 50.7 ± 10.1 years, 17 female). The groups did not differ in socioeconomic status (SES) as measured by the Hollingshead Index of Social Position (t(66) = −.56, p = .58) or by family income (t(66) =.47, p = .64). Descriptive statistics can be found in Table 1. MNPs were recruited within Madison, WI and the surrounding community using flyers, online
Results
The outcome of analyses testing for group differences in biological variables showed a significant effect of group on both cortisol AUC (F(1, 59) = 5.03, p = .029), after controlling for the effects of age and sex, and flare peak1
Discussion
Our results suggest that individuals with a long-term meditation practice experienced less stress in response to the TSST, as indicated by both self-report and salivary cortisol measures, compared to a control group with no meditation experience. Moreover, though the difference between the correlations was not statistically significant, the perception of stress in response to the TSST more closely reflected the HPA-axis response in long-term meditators, suggesting that this group may have
Conflict of interest
Dr. Richard J. Davidson serves on the board of directors for the following non-profit organizations: The Mind and Life Institute and the Center for Investigating Healthy Minds, Inc.
Contributors
MAR conceived of and designed the study, analyzed the data, and wrote the manuscript.
AL contributed to the conception and design of the study, interpretation of data, and revision of the manuscript.
DMP contributed to analysis of the data and revision of the manuscript.
DRWB contributed to data acquisition and revision of the manuscript.
BSS contributed to analysis of the data and preparation and revision of the manuscript.
DGM contributed to conception and design of the study.
RJD contributed to
Acknowledgements
This research was supported by the National Center for Complementary and Integrative Health (NCCIH) P01AT004952 to RJD & AL, a core grant to the Waisman Center from the National Institute of Child Health and Human Development (NICHD) P30HD003352 to Albee Messing, and generous donations from individuals to the Center for Investigating Healthy Minds. No donors, either anonymous or identified, have participated in the design, conduct, or reporting of research results in this manuscript.
References (87)
- et al.
Stress inhibits hair growth in mice by induction of premature catagen development and deleterious perifollicular inflammatory events via neuropeptide substance P-dependent pathways
Am. J. Pathol.
(2003) - et al.
Mindfulness-based therapy for inflammatory bowel disease patients with functional abdominal symptoms or high perceived stress levels
J. Crohn's Colitis
(2014) Stress and the inflammatory response: a review of neurogenic inflammation
Brain. Behav. Immun.
(2002)- et al.
Endothelial dysfunction in the pulmonary artery induced by concentrated fine particulate matter exposure is associated with local but not systemic inflammation
Toxicology
(2012) - et al.
How do mindfulness-based cognitive therapy and mindfulness-based stress reduction improve mental health and wellbeing? A systematic review and meta-analysis of mediation studies
Clin. Psychol. Rev.
(2015) - et al.
Mindfulness practice leads to increases in regional brain gray matter density
Psychiatry Res.
(2011) Local effector functions of capsaicin-sensitive sensory nerve endings: involvement of tachykinins, calcitonin gene-related peptide and other neuropeptides
Neuroscience
(1988)- et al.
Mindfulness-based stress reduction for healthy individuals: a meta-analysis
J. Psychosom. Res.
(2015) Enhancement of allergic skin wheal responses and in vitro allergen-specific IgE production by computer-induced stress in patients with atopic dermatitis
Brain. Behav. Immun.
(2003)- et al.
Excitatory non-adrenergic-non-cholinergic neuropeptides: key players in asthma
Eur. J. Pharmacol.
(2000)
Reduced age-related degeneration of the hippocampal subiculum in long-term meditators
Psychiatry Res.
Client preferences affect treatment satisfaction, completion, and clinical outcome: a meta-analysis
Clin. Psychol. Rev.
Long-term follow-up of internet-delivered exposure and mindfulness based treatment for irritable bowel syndrome
Behav. Res. Ther.
The role of neuropeptides in the control of regional immunity
Clin. Dermatol.
The validation of an active control intervention for Mindfulness Based Stress Reduction (MBSR)
Behav. Res. Ther.
Workplace based mindfulness practice and inflammation: a randomized trial
Brain. Behav. Immun.
Effect of compassion meditation on neuroendocrine, innate immune and behavioral responses to psychosocial stress
Psychoneuroendocrinology
Further exploring the brain-skin connection: stress worsens dermatitis via substance P-dependent neurogenic inflammation in mice
J. Invest. Dermatol.
Neurogenic inflammation in stress-induced termination of murine hair growth is promoted by nerve growth factor
Am. J. Pathol.
Recapitulating atopic dermatitis in three dimensions: cross talk between keratinocytes and nerve fibers
J. Invest. Dermatol.
Two formulas for computation of the area under the curve represent measures of total hormone concentration versus time-dependent change
Psychoneuroendocrinology
Chronic stress induces transient spinal neuroinflammation, triggering sensory hypersensitivity and long-lasting anxiety-induced hyperalgesia
Pain
Determinants of salivary alpha-amylase in humans and methodological considerations
Psychoneuroendocrinology
A comparison of mindfulness-based stress reduction and an active control in modulation of neurogenic inflammation
Brain. Behav. Immun.
Acute immobilization stress triggers skin mast cell degranulation via corticotropin releasing hormone, neurotensin, and substance P: a link to neurogenic skin disorders
Brain. Behav. Immun.
Impact of mindfulness on the neural responses to emotional pictures in experienced and beginner meditators
Neuroimage
Which is more important after total knee arthroplasty: local inflammatory response or systemic inflammatory response?
Knee
Neuropeptides and general neuronal marker in psoriasis—an immunohistochemical study
Clin. Exp. Dermatol.
Cognitive-affective neural plasticity following active-controlled mindfulness intervention
J. Neurosci.
Construct validity of the five facet mindfulness questionnaire in meditating and nonmeditating samples
Assessment
Intestinal-specific TNFα overexpression induces Crohn’s-like ileitis in mice
PLoS One
A quantitative comparison of the effect of local analgesics on argon laser induced cutaneous pain and on histamine induced wheal flare and itch
Acta Derm. Venereol.
Mindfulness meditation and improvement in sleep quality and daytime impairment among older adults with sleep disturbances
JAMA Intern. Med.
Mind-body therapies and control of inflammatory biology: a descriptive review
Brain. Behav. Immun.
Patients or volunteers? The impact of motivation for trial participation on the efficacy of patient decision AIDS: a secondary analysis of a Cochrane systematic review
Med. Decis. Making
The neuroendocrinology of social isolation
Annu. Rev. Psychol.
A new scale of social desirability independent of psychopathology
J. Consult. Psychol.
A mulitdimensional approach to individual differences in empathy
J. Pers. Soc. Psychol.
The satisfaction with life scale
J. Personal. Assess.
Self-Theories: Their Role in Motivation, Personality, and Development
The parasympathetic nervous system as a regulator of mast cell function
Methods Mol. Biol.
Effects of mindfulness-based stress reduction (MBSR) on emotion regulation in social anxiety disorder
Emotion
Association between income and the hippocampus
PLoS One
Cited by (57)
Efficacy of mindfulness to regulate induced emotions in the laboratory: A systematic review and meta-analysis of self-report and biobehavioral measures
2022, Neuroscience and Biobehavioral ReviewsDoes meditation training promote pro-environmental behavior? A cross-sectional comparison and a randomized controlled trial
2022, Journal of Environmental PsychologyEffects of two mindfulness based interventions on the distinct phases of the stress response across different physiological systems
2022, Biological PsychologyCitation Excerpt :Systematic assessment of the effects of contemplative training on the biological changes associated with stress has only recently started. The relationship between meditation practice and the attenuation of the stress response at the physiological level has been found in observational studies comparing long-term meditation practitioners and matched controls (Gamaiunova et al., 2019; Rosenkranz et al., 2016). In addition to observational research designs, several intervention studies have focused on the effects of MBIs on stress-related changes in physiological pathways.
Empowering the Health and Well-Being of the Palliative Care Workforce: Evaluation of a Weekly Self-Care Checklist
2021, Journal of Pain and Symptom ManagementCitation Excerpt :Its inclusion among the clinical standard operating procedures is intended to stress that self-care is considered a cornerstone of good clinical practice. The checklist uses evidence-based practices for increasing health and well-being32–39 and reducing stress and burnout.34,35,38,40–46 See Fig. 1 for the checklist.
Changes in hair cortisol and self-reported stress measures following mindfulness-based stress reduction (MBSR): A proof-of-concept study in pediatric hematology-oncology professionals
2020, Complementary Therapies in Clinical PracticeCitation Excerpt :Our findings could reflect an absence of biological change. One hypothesis is that it would require more practice over a longer time period to yield biological changes, as is suggested by a number of studies on experienced meditators [42,43]. The timing of the hair sample collection may also have influenced the results.
Life in Suspension with Death: Biocultural Ontologies, Perceptual Cues, and Biomarkers for the Tibetan Tukdam Postmortem Meditative State
2024, Culture, Medicine and Psychiatry