Tuesday, April 29, 2014

Stress Rx: Chant two Ommsss, with food, twice daily

How can and should meditation be used to restore physical and mental health in a clinical setting?  That is the question that Emory University neuroscience graduate student Jordan Kohn posed to begin the latest Neuroethics Journal Club.  The discussion thereafter centered on Black et al.’s 2013 Psychoneuroendocrinology paper entitled “Yogic meditation reverses NF-κB and IRF-related transcriptome dynamics in leukocytes of family dementia caregivers in a randomized controlled trial.”1 This paper laudably attempts to bridge the mind-body gap and suggests a biological, and perhaps more importantly, a genetic mechanism to explain how yoga can apparently help relieve stress, protect against depression, and restore immune function in caregivers.  The implications of this line of investigation could be widespread as the scientific and medical communities grapple with our fundamental understanding of the mind and body and how to integrate what used to be considered fringe or alternative approaches into the mainstream.

Caregivers for dementia patients have been widely studied because they experience high levels of chronic stress and in turn suffer high rates of depression and other mental and physical health problems.2 Both acute and chronic stress can drastically alter immune system function3 and, not surprisingly, dementia patient caregivers show marked impairments in immunological measures.4 The connection between the immune system and mental health is increasingly studied for its apparent bi-directionality.  Sickness behavior – characterized by fatigue, poor sleep, irritability, and lack of appetite – closely resembles major depression.  In fact, pro-inflammatory cytokines, which are up-regulated during an infection, can induce depression.4


In this study, participants were randomly assigned to practice the Kirtan Kriya Meditation, guided by an audio CD, for only 12 minutes per day, or to listen to a CD of relaxing music for the same amount of time each day.  After 8 weeks, nearly two thirds of the meditators had improved depression scale scores of at least 50% and most of them also scored 50% better than they had at baseline on a cognitive test.  Significantly fewer music listeners improved by 50% in either of these measures. These data had actually been, in part, reported previously6 but in this study the authors sought to determine whether meditation modulated gene expression in an attempt to understand how yogic meditation mechanistically elicits these beneficial effects.  Black and colleagues assessed genome-wide expression levels at baseline and post-treatment for both groups and also performed more focused analyses on genes related to immune system function or under the control of the well-known transcription factors NF-κB and IRF-1.9  They found that there was a significant reduction in the expression of genes that respond to NF- κB and an increase in those that can be activated by IRF-1 which, together would suggest a decrease in pro-inflammatory cytokines and a better functioning immune system.

This paper, along with a growing literature on the clinical benefits of meditation, raises the question of how ecologically valid such studies are and how one would, on a practical level, implement such interventions.  For one thing there is the issue of standardization.  Several high-profile meta-analyses have been performed to try to answer the question of whether meditative interventions actually improve clinical measures but only a fraction of relevant studies can be included in any one analysis due, at least in part, to the heterogeneity of interventions and study designs.7,8 This has led to poor power which has made it difficult to determine what effect these interventions actually have.9 A second question is in what contexts should meditation be most appropriately prescribed? Our journal club facilitator, Jordan Kohn, noted that meditation has been shown to be useful for people incarcerated in prison and perhaps uniquely beneficial for training the military to cultivate their ‘Warrior Minds’ (though there may be additional ethical concerns for some). However, there may not be a one-size-fits all approach to meditation. While there might be benefit for stress reduction in Alzheimer’s caregivers, or cultivating compassion in those who are incarcerated, or creating sharper minds for our military personnel, Jordan mentioned that there may be some individuals who would not find benefit and might actually be harmed, by certain kinds of meditation. For example, individuals who suffered PTSD might only relive their trauma more vividly during their meditation sessions.

An important issue that this paper speaks to indirectly is the apparent necessity to have biological data to support psychological findings.  This is undoubtedly an important pursuit as it may lead to new therapeutic targets, but it also seems to be missing the point.  Does a psychological or mind-based intervention absolutely need to affect biological measures (in the body) in order to be valid?  In this case, the reported effect is most likely indirect where meditation helps to relieve perceptions of stress which may allow hormone levels to normalize and the immune system to get back to business as usual.  Since the authors do not report effects on any of the biological “levels” between the mind and gene transcripts in immune tissue, their genetics results serve mainly to support the aforementioned psychological data but do not really extend the findings.  However, in the public one can easily find alternative medicine skeptics as well as enthusiasts who are already mesmerized by the exoticism of meditative traditions and alternative medicine. Having a biological marker as compelling as genetic data might convince skeptics that meditation has true validity and is worthy of future funding and integration into clinical care.

Another question along these lines is whether biological measures – which can be altered by meditation – can shift a sense of disease responsibility?  It is well known that not every individual who is exposed to trauma or put under stress will develop a stress-related pathology.  Some people seem to be resilient.  If the remedy for those who are not resilient is a drug that alters neurochemistry, then one would think that the susceptibility must have been due to a pre-existing chemical imbalance – a biological deficit so to speak.  But if the prescribed therapy is to train yourself in mindfulness, then does that mean the disease is the result of a character or personality flaw?  That is, if a patient can just use his/her mind to reduce stress through meditation should the patient just summon the moral fortitude to not be so affected by stress to begin with?  One wonders if prescribing something like a pill versus meditation, indicates that the patient needs “real” medicine for their illness because it is something out of the patient’s control.  These and other issues are likely to be continually discussed as alternative approaches including meditation are increasingly studied and expanded into clinical settings.


References

1.  Black, D. S. et al. Yogic meditation reverses NF-kappa B and IRF-related transcriptome dynamics in leukocytes of family dementia caregivers in a randomized controlled trial. Psychoneuroendocrinology 38, 348-355, doi:DOI 10.1016/j.psyneuen.2012.06.011 (2013).
2.  Pinquart, M. & Sorensen, S. Differences between caregivers and noncaregivers in psychological health and physical health: A meta-analysis. Psychol Aging 18, 250-267, doi:Doi 10.1037/0882-7974.18.2.250 (2003).
3.  Dhabhar, F. S. & McEwen, B. S. Acute stress enhances while chronic stress suppresses cell-mediated immunity in vivo: A potential role for leukocyte trafficking. Brain Behav Immun 11, 286-306, doi:DOI 10.1006/brbi.1997.0508 (1997).
4.  Lovell, B. & Wetherell, M. A. The cost of caregiving: Endocrine and immune implications in elderly and non elderly caregivers. Neurosci Biobehav Rev 35, 1342-1352, doi:DOI 10.1016/j.neubiorev.2011.02.007 (2011).
5.  Dantzer, R., O'Connor, J. C., Freund, G. G., Johnson, R. W. & Kelley, K. W. From inflammation to sickness and depression: when the immune system subjugates the brain. Nature reviews. Neuroscience 9, 46-56, doi:10.1038/nrn2297 (2008).
6.  Lavretsky, H. et al. A pilot study of yogic meditation for family dementia caregivers with depressive symptoms: effects on mental health, cognition, and telomerase activity. International journal of geriatric psychiatry 28, 57-65, doi:10.1002/gps.3790 (2013).
7.  Goyal, M. et al. Meditation programs for psychological stress and well-being: a systematic review and meta-analysis. JAMA internal medicine 174, 357-368, doi:10.1001/jamainternmed.2013.13018 (2014).
8.  Grossman, P., Niemann, L., Schmidt, S. & Walach, H. Mindfulness-based stress reduction and health benefits. A meta-analysis. Journal of psychosomatic research 57, 35-43, doi:10.1016/S0022-3999(03)00573-7 (2004).
9.  Bartlett, T. "Wait, So Does Meditation Actually Work or Not?" in Percolator  (Chronicle.com, 2014).
10.  NF-κB and IRF-1 are transcription factors which, when activated by an extracellular signal, can induce the expression of a variety proteins in order to mount a cellular response. NF-κB is typically associated with an increase in pro-inflammatory cytokines whereas IRF-1 induces interferon beta, an antiviral cytokine.



Want to cite this post?

Purcell, R. (2014). Stress Rx: Chant two Ommsss, with food, twice daily. The Neuroethics Blog. Retrieved on , from http://www.theneuroethicsblog.com/2014/04/stress-rx-chant-two-ommsss-with-food.html

1 comment:

Jordan Kohn said...

Great post, Ryan!

In response to some points you make in the final paragraph, it's important to keep in mind that just because a certain biological illness can be alleviated through non-pharmacological means, does not necessarily imply that it was psychosomatic in origin. Likewise, an effective pharmacological treatment does not suggest that the sickness is more "real," nor that it originated in the body (e.g. genes, neurochemistry, etc.) To think otherwise perpetuates an outdated perspective of human health as involving mind, brain, and body, as if they were somehow separate systems, when in fact they are completely interdependent - the mind cannot exist without the brain, without the body, without the mind. Two findings in PNI (among countless others) support this claim - the Black et al. study illustrating that psychosocial interventions alter inflammatory biology in white blood cells, and Dr. Andrew Miller's work using anti-inflammatory turmeric extracts to improve depressive symptoms. But change is a gradual process, particularly in the medical profession, so this paradigm shift will take time and no doubt will be expedited as public attitudes toward health shift as well.