The effect of mindfulness meditation training on biological acute stress responses in generalized anxiety disorder
Introduction
Chronic or repeated psychological stress has been associated with abnormalities in stress hormones and inflammatory markers. These hormonal and immune abnormalities are in turn associated with negative health consequences such as cardiovascular disease risk and metabolic syndrome (Chrousos, 2000, Ridker et al., 2000). For example, chronic over-secretion of cortisol is associated with metabolic and hemodynamic disturbances such as high systolic blood pressure, fasting glucose, and insulin (Kaur, 2014). In addition, higher levels of circulating pro-inflammatory cytokines such as interleukin-6 (IL-6) are associated with other metabolic syndrome elements including higher body-mass index and the development of type 2 diabetes, and with an increased risk for coronary artery disease (Pradhan et al., 2002).
The causal link between hormonal and inflammatory markers and stress suggested by this body of cross-sectional data is supported by studies showing changes in these biomarkers in response to an experimental stress. Paralleling the epidemiological observations of chronically stressed populations, laboratory stress challenge tests have thus been found to provoke similar elevations in stress hormones (cortisol and adrenocorticotropic hormone (ACTH)) and markers of inflammation (tumor necrosis factor-alpha (TNF-alpha), and IL-6) in the bloodstream (Kirschbaum et al., 1993, Pace et al., 2006, von Kanel et al., 2005).
Mindfulness-Based interventions have greatly increased in popularity and have been used to treat anxiety in recent years. However, randomized and adequately controlled trials are needed to validate waitlist-controlled findings and provide additional confirmation of biological effects (Chiesa and Serretti, 2010, Goyal et al., 2014). Given that mindfulness meditation focuses on one's present experience is often ignored or avoided in Generalized Anxiety Disorder (GAD), we conducted a randomized, controlled study comparing Mindfulness-Based Stress Reduction (MBSR), a standardized and manualized mindfulness meditation training course, with an attention control, Stress Management Education (SME) in individuals with GAD. We measured the effect of MBSR vs. SME on clinical anxiety measures, and found a greater drop in anxiety ratings in most of our measures (see (Hoge et al., 2013) for detailed results). In a group of these patients, we examined resilience to subsequent stress by measuring hormones and inflammatory markers during the laboratory-based Trier Social Stress Test (TSST). Resilience is āthe ability of individuals to adapt successfully in the face of acute stress, trauma, or chronic adversity, maintaining or rapidly regaining psychological well-being and physiological homeostasisā (Charney, 2004), and the TSST, which provides a way to measure coping and recovery from a standardized stressor, has been used to assess resilience in the laboratory (Rose et al., 2013). Prior research has demonstrated that patients with GAD, like other chronically stressed populations, have an exaggerated stress hormone response to the TSST or other laboratory stress provocation, compared to healthy controls (Gerra et al., 2000).
Although participantsā ratings of subjective stress were reduced more after MBSR compared to SME in our clinical study, we wanted to examine biomarkers in a separate planned analysis using blood markers previously linked to acute and chronic stress, such as the stress hormones cortisol and ACTH, and markers of inflammation, TNF-alpha and IL-6. We were interested in whether MBSR could improve coping and mitigate the physiological effects of acute stress. In addition, decreases in stress hormones and chronic inflammatory markers after mindfulness meditation, compared to a control intervention, would provide some support to the hypothesis that mindfulness meditation training may contribute to improvements in overall medical (cardiovascular and metabolic) health through reductions in stress related biological responses. We hypothesized that mindfulness meditation would mitigate the previously reported elevated response to acute stress observed in GAD, evidenced by a greater reduction in stress hormones and inflammatory markers with treatment.
Section snippets
Participants and procedures
The procedures of the clinical randomized controlled trial have been described in detail previously (Hoge et al., 2013). Briefly, individuals age 18 and older with GAD, as determined by the Structured Clinical Interview for the DSM-IV (SCID) (First et al., 2002), were randomized to either a modified group MBSR or group SME (see below for course descriptions). Exclusion criteria included lifetime history of psychotic disorder, intellectual disability, organic medical disorders (such as endocrine
Results
Demographic characteristics by treatment group are presented in Table 1; there were no significant differences in gender, age, or race distribution. After randomization, 11 participants from the SME group dropped out, and 3 from the MBSR group dropped. Mean values and changes in AUC concentrations for hormone and cytokine levels between before and after the 8-week treatment, are shown in Table 2.
Discussion
We found that mindfulness meditation training was associated with an attenuated stress response to laboratory stress in GAD, with evidence from both HPA axis hormones and inflammatory markers, raising the possibility that mindfulness meditation may imbue some resilience to stressful psychological challenges. The TSST is a well-validated, widely used laboratory-based model of psychological stress that can be used in a controlled fashion to understand the effects of potential real-world stressors
Funding/support
This study was primarily supported by grant K23AT4432 from the National Center on Complementary and Alternative Medicine, National Institutes of Health (Hoge, P.I.). The Highland Street Foundation provided additional support including to Ms. Palitz, Mr. Schwarz, Ms. Owens, and Drs. Bui, Pollack and Simon.
Authorship contributions
EAH, MHP, NMS, MEO and JMJ were responsible for the study conception and design; EAH, EB, SAP, and NRS analyzed and interpreted the data.
All authors participated in the drafting the article or with revising it critically for important intellectual content and all authors gave final approval of the version to be published.
Declaration of interest
Dr. Hoge reports grants from National Institutes of Health (K23AT4432) during the conduct of the study. Dr. Bui received funding from the National Institute of Health, the American Foundation for Suicide Prevention, the Highland Street Foundation, and from the U.S. Department of Defense during the conduct of the study. Ms. Palitz and Mr. Schwarz received funding from the National Institute of Health and the Highland Street Foundation during the conduct of the study. Ms. Owens received funding
Acknowledgements
The authors would like to thank Zayda Vallejo for her work in teaching the study courses, and the MGH hospital volunteers who assisted in this study, and to acknowledge nursing support from the Harvard Clinical and Translational Science Center (NIH Award #UL1 RR 025758 and financial contributions from Harvard University and its affiliated academic health care centers). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard
References (39)
- et al.
Impairment of several immune functions in anxious women
J. Psychosom. Res.
(2007) - et al.
Maintenance of a positive outlook during acute stress protects against pro-inflammatory reactivity and future depressive symptoms
Brain Behav. Immun.
(2012) - et al.
Cortisol response to a cognitive stress challenge in posttraumatic stress disorder (PTSD) related to childhood abuse
Psychoneuroendocrinology
(2003) - et al.
Mindfulness-based cognitive therapy improves emotional reactivity to social stress: results from a randomized controlled trial
Behav. Ther.
(2012) - et al.
Acute psychosocial stress: does the emotional stress response correspond with physiological responses?
Psychoneuroendocrinology
(2012) - et al.
Decreased adrenocorticotropic hormone and cortisol responses to stress in healthy adults reporting significant childhood maltreatment
Biol. Psychiatry
(2007) - et al.
Generalized anxiety disorder is associated with metabolic syndrome in the Vietnam experience study
Biol. Psychiatry
(2009) - et al.
Medial prefrontal cortex and right insula activity predict plasma ACTH response to trauma recall
Neuroimage
(2009) - et al.
Exhaustion is associated with reduced habituation of free cortisol responses to repeated acute psychosocial stress
Biol. Psychol.
(2006) - et al.
Life events and panic disorder/agoraphobia
Compr. Psychiatry
(1995)
Salivary cortisol is associated with diagnosis and severity of late-life generalized anxiety disorder
Psychoneuroendocrinology
Innate immune, neuroendocrine and behavioral responses to psychosocial stress do not predict subsequent compassion meditation practice time
Psychoneuroendocrinology
The longitudinal impact of exposure to violence on cortisol reactivity in adolescents
J. Adolesc. Health
Increasing correlations between personality traits and cortisol stress responses obtained by data aggregation
Psychoneuroendocrinology
Two formulas for computation of the area under the curve represent measures of total hormone concentration versus time-dependent change
Psychoneuroendocrinology
Anxiety and risk of incident coronary heart disease: a meta-analysis
J. Am. Coll. Cardiol.
A randomized controlled trial of a self-guided, multimedia, stress management and resilience training program
Behav. Res. Ther.
Variations in anticipatory cognitive stress appraisal and differential proinflammatory cytokine expression in response to acute stress
Brain Behav. Immun.
Psychobiological mechanisms of resilience and vulnerability: implications for successful adaptation to extreme stress
Am. J. Psychiatry
Cited by (120)
T cell-mediated skin-brain axis: Bridging the gap between psoriasis and psychiatric comorbidities
2024, Journal of AutoimmunityComparative efficacy of psychological interventions on immune biomarkers: A systematic review and network meta-analysis (NMA)
2023, Brain, Behavior, and Immunity