Medicine Miracles-The Biology of Belief 2013
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Medicine & Miracles: The Biology of Belief
Brenda Stockdale, Director of Behavioral Medicine RC Cancer Centers/Vantage Oncology Copyright – Brenda Stockdale – 2013 – All Rights Reserved www.brendastockdale.com
• “This [program], in and of itself, is a prescription for maximizing one's health." • -Anne Webster, PhD, Director, Benson-Henry Institute for Mind Body Medicine, Harvard Medical School.
Proinflammatory Effect of Stress
Miller, A., Maletic, V. & Raison, C.L. (2009). Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biological Psychiatry, 65, 732-741.
System-wide Endocrine Dysregulation • Raison, C.L., Borisov, A.S., Woolwine, B.J., Massung, B., Vogt, G. & Miller, A.H. (2010). Interferon-alpha effects on diurnal hypothalamic-pituitary-adrenal axis activity: relationship with proinflammatory cytokines and behavior. Molecular Psychiatry, 15, 535-547. • Summary: IFN-alpha/ribavirin administration was associated with significant flattening of the diurnal ACTH and cortisol slope and increased evening plasma ACTH and cortisol concentrations. These data indicate that chronic exposure to innate immune cytokines may contribute to the altered diurnal HPA axis activity and behavior found in medically ill individuals.
Tumor Microenvironment •
Pyter, L, et al. (2009). Peripheral tumors induce depressive-like behaviors and cytokine production and alter hypothalamic-pituitary-adrenal axis regulation. Proc Nat Acad Sci, Jun 2;106(22):9069-74. doi: 10.1073/pnas.0811949106.
Antoni MH, Lutgendorf SK, Cole SW, Dhabhar FS, Sephton SE, McDonald PG, Stefanek M, Sood AK. (2006). The influence of bio-behavioural factors on tumour biology: pathways and mechanisms. Nal Rev Cancer, Mar 6 (3): 240-8.
Lutgendorf, S., Sood, A., Antoni, M. (2010). Host factors and cancer progression: biobehavioral signaling pathways and interventions. J Clin Oncology, 2010 Sep 10;28(26):4094-9. doi: 10.1200/JCO.2009.26.9357.
Moreno-Smith, M., Lutgendorf, S., Sood, A. (2010). Impact of stress on cancer metastasis. Future Oncol, Dec ; 6(12): 1863–1881. doi:10.2217/fon.10.142.
Raison, C., Miller, A. (2011). Is depression an inflammatory disorder? Curr Psychiatry Rep, Dec;13(6):467-75. doi: 10.1007/s11920-011-0232-0.
Lamkin, D., Sloan, E., Patel, A., Chiang, B., Ma, J., Arevalo, J., Morizono, K., Cole, S. (2012). Chronic stress enhances progression of acute lymphoblastic leukemia via β-adrenergic signaling. Brain Behav Immun, May;26(4):635-41. doi: 10.1016/j.bbi.2012.
Tumor Survival, Proliferation, Angiogenesis • L Antonova and C Mueller. (2008). Hydrocortisone down-regulates the tumor suppressor gene BRCA1 in mammary cells: a possible molecular link between stress and breast cancer. Genes, Chromosomes and Cancer, 47: 341-52. • E Yang et al. (2006). Norepinephrine Up-regulates the Expression of Vascular Endothelial Growth Factor, Matrix Metalloproteinase (MMP)-2, and MMP-9 in Nasopharyngeal Carcinoma Tumor Cells. Cancer Research, 66: 10357-64. • K Sastry et al. (2006). Epinephrine Protects Cancer Cells from Apoptosis via Activation of cAMP-dependent Protein Kinase and BAD Phosphorylation. The Journal of Biological Chemistry, 282: 14094-10.
Insulin Resistance/Blue Light •
Spiegel, K., Knutson, K., Leproult, R., Tasali, E., Van Cauter, E. (2005). Sleep loss: a novel risk factor for insulin resistance and Type 2 diabetes. J Appl Physiol 99: 2008 –2019, doi:10.1152/japplphysiol.00660.
Stevens, R. (2009). Light-at-night, circadian disruption and breast cancer: assessment of existing evidence. International Journal of Epidemiology, 2009;38:963–970. doi:10.1093/ije/dyp178.
Aube ́ M, Roby J, Kocifaj M (2013). Evaluating Potential Spectral Impacts of Various Artificial Lights on Melatonin Suppression, Photosynthesis, and Star Visibility. PLoS ONE, 8(7): e67798. doi:10.1371/journal.pone.0067798.
Kloog, I., Stevens, R., Haim, A., Portnov, B. (2010). Nighttime light level co-distributes with breast cancer incidence worldwide. Cancer Causes Control, Dec;21(12):2059-68. doi: 10.1007/s10552-010-9624-4.
Kloog, I., Haim, A., Stevens, R., Portnov, B. (2009). Global co-distribution of light at night (LAN) and cancers of prostate, colon, and lung in men. Chronobiol Int, Jan;26(1):108-25. doi: 10.1080/07420520802694020.
Lockley, S., Brainard, G., Czeisler, C. (2003). High Sensitivity of the Human Circadian Melatonin Rhythm to Resetting by Short Wavelength Light. J Clin Endoc Metab, 88(9): 45024505.
Sleep & Cardiovascular Disease • Naska, A., et al. (2007). Siesta in Healthy Adults and Coronary Mortality in the General Population. Archives of Internal Medicine, 167, 296-301. • Leineweber C, Kecklund G, Orth-Gomér K. (2007). Prediction of cardiocerebrovascular and other significant disease from disturbed sleep and work strain. Scandinavian Journal of Work, Environment and Health, Jun;33(3):215-22. • Loponen, M., Hublin, C., Kalimo, R., Mänttäri, M., Tenkanen, L. (2010). Joint effect of self-reported sleep problems and three components of the metabolic syndrome on risk of coronary heart disease. Journal of Psychosomatic Research, 68, 149-58.
Cardiovascular Disease • Surtees, P., et al. (2008). Psychological distress, major depressive disorder, and risk of stroke. Neurology, Mar 4;70(10):788-94. doi: 10.1212/01.wnl.0000304109.18563.81 • Virani, S., Khan, A., de Marchena, E. (2007). Takotsubo Cardiomyopathy, or Broken-Heart Syndrome. Tex Heart Inst J, 34:76-9. • Madias, J. (2013). Frequency of takotsubo cardiomyopathy in postmenopausal women presenting with an acute coronary syndrome: still underdiagnosed. Am J Cardiol, Aug 1;112(3):464-5. doi: 10.1016/j.amjcard.2013.05.046.
• Dong, M., Giles, W., Felitti, V., Anda, R., et al. (2004). Insights Into Causal Pathways for Ischemic Heart Disease : Adverse Childhood Experiences Study. Circulation, 110:1761-1766. • Ma, W., Chen, H., Jiang, L., Song, G., Kan, H. (2011). Stock volatility as a risk factor for coronary heart disease death. European Heart Journal, 32, 1006–1011, doi:10.1093/eurheartj/ehq495.
Depression • Felger, J., Alagbe, O., pace, T., Woolwine, B., Hu, F., Raison, C., Miller A. (2011). Early activation of p38 mitogen activated protein kinase is associated with interferonalpha-induced depression and fatigue. Brain Behav Immun. August; 25(6): 1094. • Cohen, L., Cole, S., Sood, A., Prinsloo, S., et. al. (2012). Depressive symptoms and cortisol rhythmicity predict survival in patients with renal cell carcinoma: a role of inflammatory signaling. PLoS One, 2012;7(8):e42324. doi: 10.1371/journal.pone.00423 • Miller, A., Maletic, V., Raison, C. (2009). Inflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression. Biol Psychiatry. May 1; 65(9): 732–741. doi:10.1016/j.biopsych.2008.11.029. • Pyter, L., Pineros, V., Galang, J., McClintock, M., Prenderrast, B. (2009). Peripheral tumors induce depressive-like behaviors and cytokine production and alter hypothalamic-pituitary-adrenal axis regulation. Proc Nal Acad Sciences, 2;106(22):9069-74. doi
Post Traumatic Stress Disorder (PTSD) •
26% of cancer survivors exhibited criteria for current or lifetime diagnoses of PTSD: Stukas, A., et al. (1999). PTSD in Heart Transplant Recipients and Their Primary Family Caregivers. Psychosomatics, 40, 212-221. Contribution to allostatic load: Temoshok, L., Waldstein, S., Wald, R., GarzinoDemo, Al, Synowski, S., Sun, L. & Wiley, J. (2008). Type C coping, alexithymia, and heart rate reactivity are associated independently and differentially with specific immune mechanisms linked to HIV progression. Brain, Behavior and Immunity, 22, 781-792. Boscarino, J. (2004). Posttraumatic stress disorder and physical illness: results from clinical and epidemiologic studies. Annals of the New York Academy of Sciences, 1032, 141-53. Increase in all cause mortality: Ladwig, K., et al. (2008). Posttraumatic stress symptoms and predicted mortality in patients with implantable cardioverterdefibrillators: results from the prospective living with and implanted cardioverter-defibrillator study. Archives of General Psychiatry, 65, 1324-30. O’Donovan, A., et al., (2011). Childhood Trauma Associated with Short Leukocyte Telomere Length in Posttraumatic Stress Disorder. Biological Psychiatry, DOI: 10.1016/j.biopsych.2011.01.035.
Post Traumatic Stress Disorder (PTSD) •
Pace, T., Heim, C. (2011). A short review on the psychoneuroimmunology of posttraumatic stress disorder: from risk factors to medical comorbidities. Brain Behav Immun. Jan;25(1):6-13. doi: 10.1016/j.bbi.2010.10.003.
Pace, T., Wingenfeld, K., Schmidt, I., Meinlschmidt, G., Hellhammer, D., Heim, C. (2012). Increased peripheral NF-κB pathway activity in women with childhood abuse-related posttraumatic stress disorder. Brain Behav Immun. Jan;26(1):13-7. doi: 10.1016.
Pace, T., Wingenfeld, K., Schmidt, I., Meinlschmidt, G., Hellhammer, D., Helm, C. (2012). Increased peripheral NF-kB pathway activity in women with childhood abuse-related posttraumatic stress disorder. Brain Behav Immun, Jan;26(1):13-7. doi: 10.1016/j.bb.
Pace, T., Mletzko, T., Alagbe, O., Musselman, D. Nemeroff, C., Miller, A., Heim, C., (2006). Increased stress-induced inflammatory responses in male patients with major depression and increased early life stress. Am J Psychiatry. Sep;163(9):1630-3.
Fagundes, C., Glaser, R., Kiecolt-Glaser, J. (2013). Stressful early life experiences and immune dysregulation across the lifespan. Brain, Behav Immun, 27:8-12.
Inflammation/Infection • Clays, E., et al. (2005). Associations Between Dimensions of Job Stress and Biomarkers of Inflammation and Infection. Journal of Occupational and Environmental Medicine, 47, 878-83. • Cohen, S., Janicki-Deverts, D. & Miller, G.E. (2007). Psychological stress and disease. Journal of the American Medical Association, 298, 1685-1687. • Kemeny, M., Shedlowski, M. (2007). Understanding the interaction between psychosocial stress and immunerelated diseases: a stepwise progression. Brain, Behavior and Immunity, 21: 1009-18.
Life Stress • Epel, E., Blackburn, E., et al. (2004). Accelerated telomere shortening in response to life stress. Proc Natl Acad Sci, Dec 7;101(49):17312-5. • K Lillberg et al. (2003). Stressful life events and risk of breast cancer in 10,808 women, a cohort study. Am J Epidemiol, 157: 415-23. • Cohen, S., Janicki-Deverts, D. & Miller, G.E. (2007). Psychological stress and disease. JAMA, 298, 1685-1687. • Dube, S., Fairweather, D., et al. (2009). Cumulative Childhood Stress and Autoimmune Diseases in Adults. Psychosom Med. Feb; 71(2): 243–250. doi:10.1097/PSY.0b013e3181907888. • Brown, D.W., Anda, R.F., Felitti, V.J., Edwards, V.J., Malarcher, A.M., Croft, J.B., & Giles, W.H. (2010). Adverse childhood experiences and the risk of lung cancer. BMC Public Health, 10, 20. • Thornton, L., Andersen, B., Carson, W. (2008). Immune, endocrine, and behavioral precursors to breast cancer recurrence: a case-control analysis. Cancer Immunology, Immunotherapy, 57:1471-81.
Chronic Stress • • • • • • • • • •
Shrink Hippocampus / Increase proinflammatory cytokines Lower antioxidant levels Reduce Natural Killer cells Shrink telomeres Negatively affect insulin sensitivity Increase platelet aggregation Adversely affect endothelium Reduce Nitric Oxide levels Degrades bone Adversely impact genetic expression
The Genie in Your Genes
• Health and behavior assessment procedures are used to identify the psychological, behavioral, emotional, cognitive and social factors important to the prevention, treatment, or management of physical health problems. The focus of the assessment is not on mental health, but on the biopsychosocial factors important to physical health and treatments. The focus of the intervention is to improve the patient’s health and well being utilizing cognitive, behavioral, social and/or psychophysiological procedures designed to ameliorate specific disease-related problems. Codes 96150-96155 describe services associated with an acute or chronic illness (not meeting criteria for psychiatric diagnosis), prevention of a physical illness or disability, and maintenance of health, not meeting criteria for a psychiatric diagnosis, or representing a preventive medicine service.
Change Your Hormones in 2 minutes
Carney, D., Cuddy, A., Yap, A. (2010). Power Posing: Brief Nonverbal Displays Affect Neuroendocrine Levels and Risk Tolerance. Psychological Science, DOI: 10.1177/0956797610383437. 20
Vice Versa • Harvard business school & other r/s showcasing posture, facial expression changing hormones. • Peper, E., Lin, I-Mei. (2012). Increase or Decrease Depression: How Body Postures Influence Your Energy Level. Biofeedback, 40 (3):125-130. • Carney, D., Cuddy, A., Yap, A. (2010). Power Posing: Brief Nonverbal Displays Affect Neuroendocrine Levels and Risk Tolerance. Psychological Science, DOI: 10.1177/0956797610383437.
A little training can go a long way... • • • • • • • • •
Salutary effects on insulin levels Blood pressure regulation Increases Nitric Oxide Lowers cortisol: systemic benefits Regulates Autonomic Nervous System Multiple benefits on Enteric Nervous System (enhances nutrient absorption, etc.) Salutary effects on the regulatory patterns of sleep and wakefulness Normalizes platelet aggregation Protects bone health, memory, increases cellular oxygenation, reducing favorable environment for ca cells Increases size of hippocampus & pleasure centers of brain Assists in reframing crisis as challenge
Correct Maladaptive Response Cognitive Behavioral Stress Management • Antoni M, Lechner S, Diaz A, Vargas S, et al. (2009). Cognitive behavioral stress management effects on psychosocial and physiological adaptation in women undergoing treatment for breast cancer. Brain Behav Immun, Jul;23(5):580-91. • Antoni, M., Lutgendorf, S., et al. (2012). Cognitive-behavioral stress management reverses anxiety- related leukocyte transcriptional dynamics. Biol Psychiatry. Feb 15; 71(4): 366–372. doi:10.1016/j.biopsych.2011.10.007. •
Results: Baseline negative affect was associated with >50% differential expression of 201 leukocyte transcripts, including upregulated expression of pro-inflammatory and metastasis-related genes. CBSM altered leukocyte expression of 91 genes by >50% at follow-up (group x time interaction), including downregulation of pro-inflammatory and metastasis-related genes and upregulation of type I interferon response genes. Promoter-based bioinformatic analyses implicated decreased activity of NF-kB/Rel and GATA family transcription factors and increased activity of interferon response factors and the glucocorticoid receptor as potential mediators of CBSM-induced transcriptional alterations.
Death Valley temp range • February - Monthly averages – High 73 – Low 46
Death Valley National Park
The Writing Cure •
Stockdale, B. “Writing in Physical and Concomitant Mental Illness: Biological Underpinnings and Applications for Practice,” In Research on Writing Approaches in Mental Health, (In Press). Eds. Luciano L’Abate & Laura Sweeny. Emerald Group Publishing Ltd. Low, C., Stanton, A., Bower, J. & Gyllenhammer, L. (2010) A randomized controlled trial of emotionally expressive writing for women with metastatic breast cancer. American Journal of Gastroenterology, 105, 2440-8. Morgan, N., Graves, K., Poggi, E., Cheson, B. (2008). Implementing an expressive writing study in a cancer clinic. The Oncologist, 13, 85-93.
Is it a message I want to receive? • Sherman, D., Bunyan, D. & Creswell D. (2009). Psychological vulnerability and stress: The effects of self-affirmation on sympathetic nervous system responses to naturalistic stressors. Health Psychology, 28, 554-562. • Levy, B., Hausdorf, J., et al. (2000). Reducing Cardiovascular Stress with Positive Self-Stereotypes of Aging. The Journals of Gerontology Series B: Psychological Sciences and Social Sciences, 55, 205-13.
Diane & Hillbilly: Corneal Scarring
Medical Imagery • “If similar results were achieved with a medication, it would be prescribed routinely by anesthesiologists and surgeons as part of a presurgical regimen, and I hope that this study will help us move toward the day when presurgical preparation using guided imagery becomes the standard of care.”--Martin Rossman, M.D. • D Schwabb et al. (2007). A Study of Efficacy and Cost-effectiveness of Guided Imagery as a Portable, Self-administered, Presurgical Intervention Delivered by a Health Plan. Advances in Mind-Body Medicine, 22: 8-14 • Lang E, Benotsch E, Fick L, et al. (2000). Adjunctive nonpharmacological analgesia for invasive medical procedures: a randomized trial. Lancet, 355:1486-1490. • Osborne, T., Raichle, K., Jensen, M. (2006). Psychological interventions for chronic pain. Phys Med Rehabil Clin N Am, 17:415-433.
Frank: Metastatic Pancreatic Cancer
Frank - 14 years later
Sherry: Insulin Resistance, High BP • 6 months later lost 30 pounds, blood pressure normal, off Metformin.
Outcome Studies •
• • •
Hölzel, B.K., Carmody, J., Evans, K.C., Hoge, E.A., Duse, J.A., Morgan, L., Pitman, R.K., Lazar, S.W. (2010). Stress Reduction Correlates with Structural changes in the Amygdala. Social Cognitive and Affective Neuroscience, 5, 11-17. J Astin et al., “Mind-body medicine: state of the science, implications for practice,” Journal of the American Board of Family Practice, 16 (2003): 131-147. B Andersen, et al., “Distress reduction from a psychological intervention contributes to improved health for cancer patients,” Brain, Behavior and Immunity, 21 (2007): 953-61. F Fawzy et al., “Malignant Melanoma: Effects of an Early Structured Psychiatric Intervention, Coping and Affective State on Recurrence and Survival 6 Years Later, “ Archives of General Psychiatry, 50 (1993):681-89. R. Schneider et al., “Long-term effects of stress reduction on mortality in persons > or = 55 years of age with systemic hypertension,” The American Journal of Cardiology, 95 (2005):1060-4. B Andersen et al., “Psychological, behavioral, and immune changes following a psychological intervention. A clinical trial.” Journal of Clinical Oncology, 22 (2004): 357080. Dusek, J. & Benson, H. (2009). Mind-Body Medicine: A model of the Comparative Clinical Impact of the Acute Stress and Relaxation Responses. Minnesota Medicine, 92, 47-50. R. Schneider et al., “Long-term effects of stress reduction on mortality in persons > or = 55 years of age with systemic hypertension,” The American Journal of Cardiology, 95 (2005):1060-4.
Mindfulness • “Recent studies of mindful awareness practices reveal that it can result in profound improvement in a range of physiological, mental, and interpersonal domains of our lives... Cardiac, endocrine, and immune functions are improved with mindful practices.” -- Dan Siegel, MD
Mindfulness-Based Stress Reduction (MBSR) • Baer, R. (2006). Mindfulness training as a clinical intervention: A conceptual and empirical review. Clinical Psychology: Science and Practice, 10, 125-43. • Allen, N., et al. (2006). Mindfulness-based psychotherapies: a review of conceptual foundations, empirical evidence and practical considerations. Australian and New Zealand Journal of Psychiatry, 40, 285-94. • Grossman, P., et al. (2004). Mindfulness-based stress reductions and health benefits: A meta-analysis. Journal of Psychosomatic Research, 57, 35-43. • Creswell, J., Way, B., Eisenberger, N., et al., (2007). Neural correlates of dispositional mindfulness during affect labeling. Psychosomatic Medicine, 69, 560-565. • Pace, T.W., Negi, L.T., Adame, D.D., Cole, S.P., Sivilli, T.I., Brown, T.D., Issa, M.J. & Raison, C.L. (2009). Effect of compassion meditation on neuroendocrine, innate immune and behavioral responses to psychosocial stress. Psychoneuro Endo-crinology, 34, 87-98.
Long-term Benefits • Hölzel, B.K., Carmody, J., Evans, K.C., Hoge, E.A., Duse, J.A., Morgan, L., Pitman, R.K., Lazar, S.W. (2010). Stress Reduction Correlates with Structural changes in the Amygdala. Social Cognitive and Affective Neuroscience, 5:11-17. • Hölzel, B., et al. (2011). Mindfulness practice leads to increases in regional brain gray matter density. Psychiatry Res. Jan 30; 191(1): 36–43.
Summary of Risk Factors • • • • • • • •
Chronic exposure to stress hormones (proinflammatory cytokines) Adverse Childhood Experience (The ACE Study) Lack of control PTSD Depression Alexithymia Explanatory style Lack of meaningful connections/ Social isolation
6 Week M/B Medicine Program •
Psychophysiological evidence; Epigenetics; Mind/body mediation systems; Stress response; Diaphragmatic breathing; Biofeedback
Medical Imagery: Visual cortex, Auditory cortex, Sensory cortex-Limbic level; Creative problem solving; Potentiating placebo response; RR response; Eriksonian hypnosis, etc.
Physics of Sound--Good vibrations: Resonance; Sympathetic reverberation; Isomoodic principle; Psychoacoustics, etc., Sound survey; Energy evaluation; Regulatory rhythms sleep/wakefulness
Narrative Medicine: ACE Study; Alexithymia; Emotional identification, etc.
Biology of Belief--Neuroscience: Cultivating resilience, Optimism, Curiosity, Novelty and Enrichment; Survivor traits; Exercise
Meaning making: CBT, Mindfulness Based Stressed Reduction (MBSR)
Carolyn: “Chronic” Lyme
Brenda Stockdale, Director of Mind/Body Medicine RC Cancer Centers/Vantage Oncology www.brendastockdale.com 678-393-0066