Stress is a crucial evolutionary survival response to threat which produces a cascade of signalling within the brain and body to allow us to flight from or fight the threat. The hormones, cytokines and neurotransmitters released are of protective benefit under acute conditions, however, this response is toxic when cumulative, if not switched off, becoming chronic. Chronic stress and its subsequent and persistent impact on the body is linked with a multitude of (and often times, a combination of) physical, mental and emotional issues including cancer, chronic pain, inflammatory disorders, depression, anxiety disorders, and impaired cognitive functioning. Regardless of how chronic stress manifests in an individual, the impact on quality of life and life span can be significant, therefore measures to attenuate the perception of stress and one’s stress response is paramount in improving outcomes.
Mindfulness is an ancient practice with Buddhist origins as far back as the first century BC. Research into the variations of mindfulness-based interventions show the practice effective in reducing the stress-adaptive state, or as McEwen (1998) terms it, the ‘allostatic load’. One such intervention, combining centuries old wisdom with modern-day science is the Mindfulness Based Stress Reduction (MBSR) programme, developed by Jon Kabat-Zinn in the late 1970’s to support those suffering from a range of physical conditions for which chronic stress as an underlying factor.
MBSR is a structured, standarised 8-week programme with clearly defined weekly protocols conducted in group sessions, home practice and a one-day retreat. Traditional mindfulness teachings are covered as well as practical tools including yoga and meditation with the aim of teaching and supporting participants in dealing with their perception of stress and their response to it by developing a non-judgemental awareness of the present moment. The perception of stress is an important distinction here, as participants are taught how to change how they react to a stressor, observing the stressor (whether external or internal) non-judgementally thereby diminishing the stressor’s influence or power.
Because of its standardised approach, MBSR is a useful tool for research, particularly when comparing results across multiple studies with otherwise varying designs.
From the beginnings of the MBSR programme, self-report or subjective measures were used to ascertain and record changes experienced after the 8-week programme, however, by their very nature, subjective measures are prone to individual interpretation, cognitive bias and opinion which can impact on the results and the validity of studies into the effects of MBSR. Therefore increasingly, biomarkers are used either instead of, or in combination with, subjective measures. Due to the potential for bias in subjective measures, some studies show significantly relevant changes in objective measures but no significance in subjective measures. In the Marcus et al (2003) study, a statistically significant reduction cortisol was reported, whilst the results from the subjective Perceived Stress Scale (PSS) were not. If only PSS was used in this study, MBSR would not been shown to be effective. This highlights the importance of using objective measures such as validated biomarkers to determine the robust legitimacy of MBSR to support its use in clinical settings and acceptance as a mainstream therapy.
Through fMRI studies, Fox et al (2006) identified two attentional networks – the top-down functioning or dorsal attentional network, which is voluntary (therefore can be controlled and selective), goal-orientated and focussed; and the bottom-up or ventral attentional network which is involuntary (therefore automatic) and driven by stimulus. Guendelman et al (2017) refer to the top-down system as ‘explicit emotion regulation’, and the bottom-up as the ‘emotion generation and implicit emotion regulation’ and that therefore mindfulness practices change the bottom-up attentional network. As this network is involved in automatic response to salient stimuli, this therefore would be involved in the survival stress response, whereas the top-down network would regulate reactivity.
In coordinating this automatic response, a number of interrelated body systems are involved in the reaction to and regulation of the stress response. Accordingly, there are multiple biomarkers within these systems that can be used by researchers to objectively measure the effects of MBSR including the hypothalamic-pituitary-adrenal (HPA) axis (biomarkers include cortisol and adrenocorticotrophic hormone (ACTH)); metabolic processes (biomarkers include glucose and cholesterol); the immune system (biomarkers include cytokines and C-reactive protein); and cardiovascular markers such as heart rate variability and blood pressure (Noushad et al, 2021) (McEwen, 1998).
The stress hormone cortisol is a widely used and well evidenced biomarker with the flexibility of being measured through saliva, urine, blood and hair allowing relative accessibility for researchers and participants (Matousek et al, 2010).
Multiple studies have been published examining changes in cortisol levels following MBSR, overall supporting MBSR, including O’Leary et al. (2016) who reviewed six cortisol studies, two of which were RCTs looking at MBSR with positive albeit inconclusive findings, citing methodological differences.
A range of alternative biomarkers have been used with beneficial results. Reive (2019) reviewed 67 studies using one or a combination of 15 biological assessments including heart rate variability, blood pressure, ACTH, fasting glucose, cytokines, HbA1C and C-reactive protein in the context of MBSR and top-down / bottom-up regulation. The overall summary was in support, although tentatively, of MBSR’s regulation of stress biomarkers to the benefit of the participant. Interestingly Reive’s (2019) view is that unless cortisol is measured multiple times a day or is taken from hair, it is not a reliable measure due to its fluctuations (although, like a tree ring this would not be a dynamic record).
A range of limitations are common across multiple studies including small sample size, insufficient follow-up, non-adherence to the full 8-week MBSR programme, single day of sample-taking, (particularly in studies using cortisol as the biomarker), potential for lax participant compliance (for example, not measuring Cortisol Awakening Response (CAR) the moment of waking), or lack of control group or baseline measures (Reive, 2019). These limitations allow for large potential for expanding and fine-tuning future studies, perhaps conducting studies using a combination of biomarkers such as cortisol, cytokines and dehydroepiandrosterone (DHEA) as the interconnected mediators work together (Matousek et al, 2010). Consideration could also be taken to ensure pre and post measurements are taken on the same day of the week. In a study with 74 full-time employed participants, Kim et al. (2010) found CAR higher on workdays which they hypothesised was due to anticipating or preparing for a stressful workday ahead.
An approach published by Nath & Thapliyal (2021) that may mitigate many of these limitations is a smart wristband detecting stress across four physiological signals, namely Electrodermal Activity, Blood Volume Pulse, Inter-Beat Interval and Skin Temperature. The data points a device like this could provide throughout the MBSR programme and well-beyond the study for follow-up, would be considerable and highly valuable. In the meantime, regardless of the study design, and whilst studies could be improved and the limitations addressed, the sheer number and depth of the studies publishing the beneficial results on stress biomarkers, whether in cancer patients, those with chronic pain, anxiety or hypertension, is evidence to suggest there is a significant effect, particularly when coupled with the seemingly lack of published contradictions or counter-arguments of MBSR’s effect.
It is well established that certain foods attenuate neuro-inflammation whilst others increase it (Dias et al., 2012) (Kiecolt-Glaser, 2010). It is also generally accepted that exercise attenuates the stress response (Di Liegro et al., 2019). Therefore, should participants in future studies be matched for exercise and nutritional factors, not just age and gender? Grouping individuals with an inflammatory diet and sedentary lifestyle separate to those with a nutritious diet who exercised daily, and comparing the differences (if any) in the results. McEwen (1998) states that an individual’s level of physical health is one of the factors that can determine how they will perceive and therefore respond to a stressor. Does it stand to reason then, that the value of a biomarker in a ‘healthy’ individual would not necessarily have the same weight as that in an ‘unhealthy’ individual. A healthy person, as evidenced by the research, should have lower stress markers (as they are undertaking activities outside of MBSR that attenuate their stress response), therefore if their markers were high, would this have more significance than the same level in an unhealthy person, where such a rating would be expected due that person not undertaking activities in their daily life to bring down their stress response.
A post-MBSR consultation could determine if a calibration was required to adjust for any out-of-the-ordinary occurrences during the study. If a participant’s biomarker did not reduce was it because MBSR was not effective, or was it because their partner left them, or they were at risk of being made redundant from their job for example.
As an aside, even if MBSR was found to not significantly attenuate biological stress markers, the practice should not necessarily be discounted. The benefits of mindfulness have a range of benefits to an individual’s daily life including self-acceptance, non-judgement and self-awareness, which support a person to live life with more ease. Likened to the argument around climate change – even if lowering toxic pollution and emissions did nothing at all to affect a reduction in global warming, the population would still benefit from the subsequent cleaner air.
The use and validation of biomarkers is important to ascertain the tangible objective resulting benefits of MBSR, a programme showing promising benefits for those with physical, mental and emotional disorders. Results to date warrant further investigation in this area, with data supporting the need for studies with larger sample sizes and more robust design. Whilst only an 8-week programme, the tools and techniques learned through the programme can last a lifetime, the benefits of which impacting the individual’s quality of life and the ease in which they flow through it. Thus, further studies to increasingly show the benefits will ensure a more mainstream adoption by clinicians, their patients, and the general public.
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