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Bridging the gap between emotion and health

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I gave this presentation to the Faculty of Medicine at the University of São Paulo in Ribeirão Preto, Brazil March 2014

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Bridging the gap between emotion and health

  1. 1. Bridging the gap from emotion to health: A synthesis on vagal function Dr Andrew Kemp, PhD Associate Professor, University of Sydney Visiting Professor, University of São Paulo Editor, PLOS ONE, Frontiers in Psychology email: andrew.kemp@sydney.edu.au; twitter: @andrewhkemp
  2. 2. The Devastating Impact of Mental Illness The cost of mental & physical illness is increasing › Cost of mental illness alone – $2.5T in 2010 – estimated to increase to $6T by 2030 › But what do these figures mean? - Entire global health spending in 2009 was $5.1T - Annual GDP for low income countries is less than $1T - Entire overseas development aid over the past 20 years is less than $2T › Cost of mental health, cardiovascular disease, chronic respiratory disease, cancer, & diabetes over next two decades estimated at: - cumulative output loss of $47T - or 75% of global GDP in 2010 NIMH Director, Tom Insel: http://www.nimh.nih.gov/about/director/2011/the-global-cost-of-mental-illness.shtml
  3. 3. Intimate Relationship bw Mental & Physical Health › Participants were photographed before and after a 30-day meditation retreat against a consistent background › Day 1: each person was asked to consider what they were looking for in the practice period ahead › Meditation practice: - practice continues all morning, afternoon, & evening until about 9 or 10 p.m. - centered on mindfulness meditation (‘shamatha’ meditation) - alternating sitting and walking meditation in the meditation hall - mindful eating (inc Japanese Zen practice called oryoki) › After 30-days of meditation: each participant in the project was asked to consider what the experience of mediation retreat had been for them http://shambhalatimes.org/2011/10/20/before-and-after-portraits-from-dathun/ 3
  4. 4. Before vs after 30 day meditation retreat 4 Peter Seidler, Before and After Project, 2011
  5. 5. 5 Before vs after 30 day meditation retreat Peter Seidler, Before and After Project, 2011
  6. 6. 6 Before vs after 30 day meditation retreat Peter Seidler, Before and After Project, 2011
  7. 7. 7 Before vs after 30 day meditation retreat Peter Seidler, Before and After Project, 2011
  8. 8. 8 Before vs after 30 day meditation retreat Peter Seidler, Before and After Project, 2011
  9. 9. 9 Before vs after 30 day meditation retreat Peter Seidler, Before and After Project, 2011
  10. 10. Medical consequences of Depression Gold & Chrousos, Molecular Psychiatry, 2002, 7: 254-75 10 Abnormalities Typical symptoms (& more commonly researched) Increasing knowledge on other abnormalities including autonomic function, metabolic syndrome & morbidity
  11. 11. Reduced Bone Density in Depression  Osteoporosis Trabeculations (spongy bone) are Gold & Chrousos, Molecular Psychiatry, 2002, 7: 254-75 11 reduced Cortical bone is also thinner
  12. 12. Coronary Heart Disease ELSA-Brasil is the first large multi-centre cohort study of adult health conducted in Brazil and is funded by its Ministries of Health, and Science and Technology. Kemp & colleagues, under review
  13. 13. Relationship bw Depression & Cardiac Mortality › N=2847, 55 – 85 years › Followed-up over 4 yrs › Finding observed after adjustment for confounders - smoking, alcohol, BP, BMI & antidepressants › Depression increases relative risk of cardiac mortality 3-4 fold › Mechanisms proposed: - Decreased heart rate variability - Impaired platelet functions - Hypercortisolemia - Lifestyle factors Penninx et al.., 2001. Arch Gen Psychiatry. Without CVD (n=2397) With CVD (n=450)
  14. 14. Psychological Distress  Mortality N=65,000 people from the general population free of CVD & cancer at study baseline. Dose–response association bw psychological distress & increased risk of mortality over 8 years Russ et al., 2012, BMJ
  15. 15. Summary of Talk: From Neuroscience to Public Health › Neuroscience of emotion - basic emotion theorists vs psychological constructionists - neuroscience research is at a cross-roads › Bridging the gap from emotion to health - neurovisceral integration & importance of the vagus nerve (Thayer) - polyvagal theory (Porges, 2011): implications for emotion & mental health - cholinergic anti-inflammatory reflex (Tracey, 2002): mechanism linking impaired vagal function to physical health - vagal function: the structural link? › Frontiers Research Topic: call for contributions
  16. 16. The Emotional Brain
  17. 17. Charles Darwin on Emotion (1872) › The Expression of Emotions in Man and Animals - facial expressions reflect actions necessary for life - emotions are ‘hardwired’, innate & universal - similarities across different cultures & species e.g. anger/aggression - Frowning: protects eyes in anticipation of attack Ref: Darwin, 1872; Dalgleish, 2004
  18. 18. Paul Ekman’s 6 Basic Emotions Anger Disgust Fear Happiness Sadness Surprise Carroll Izard: distinct emotions appear within the first months of life
  19. 19. Emotions as ‘Natural Kinds’ Disgust: insula Fear: amygdala From: Lindquist et al., 2013 Anger: OFC Sadness: ACC
  20. 20. But are emotions a construct of social reality? What emotion is expressed here? Ref: Barrett, 2012
  21. 21. Social reality? Ref: Barrett, 2012 And now?
  22. 22. Emotions as Psychological Constructions From: Lindquist et al., 2013 Emotion are made up of elements: Core affect Conceptualisation Language Executive attention
  23. 23. The Emotional Brain LeDoux: Research on emotion has increased exponentially over the last decade, yet ‘emotion’ remains ill-defined, leading to an “intellectual stalemate” Lindquist: “Over the last century, the emotion debate has been fought like a series of battles that resemble something like the Hundred Years’ War between England and France.” LeDoux, 1998, 2012; Lindquist et al., 2013
  24. 24. William James on Emotion (1884) “Does your heart pound because you are afraid... Or are you afraid because you feel your heart pounding?”
  25. 25. Modern neuroscience is ‘neurocentric’ “Unfortunately, most researchers in psychiatry and psychology express little interest in the mapping of autonomic regulation as a “vulnerability” dimension for various disorders and behavioural problems, although visceral features are often symptoms of the disorders they are treating.” 25 - Stephen Porges, The Polyvagal Theory, 2011, page 261 “Techniques such as human neuroimaging permit valuable insights into the brain basis of perceptions, thoughts, feelings, and actions, yet these mental functions are for the most part considered in isolation from the physiological state of the body.” - Critchley & Harrison, 2013. Neuron
  26. 26. 26
  27. 27. Bodily Maps of Emotions In five experiments, participants (n = 701) were shown two silhouettes of bodies alongside emotional words, stories, movies, or facial expressions. Nummenmaa et al., 2013. PNAS.
  28. 28. Culturally universal categorical somatotopic maps
  29. 29. Neurovisceral Integration & Emotion Nucleus Tractus Solitarius: a site of anatomical convergence of visceral inputs, which projects to regions contributing to coordinated autonomic, hormonal & immune output Thayer et al. (2009). Neurovisceral Integration Model Porges, 2011. The Polyvagal Theory
  30. 30. Depression & CVD: Potential Mechanisms? › Increased HPA-axis activity › Increased sympatho-adrenomedullary activity › Increased inflammation › Increased platelet activation and aggregation › and reduced vagal function (heart rate variability, or HRV) Musselman, D. L. et al. 1998. Archives of General Psychiatry; Nemeroff, C. B., & Goldschmidt-Clermont, P. J. 2012. Nat. Rev. Cardiol
  31. 31. The Vagus Nerve Bonaz et al., Neurogastroenterol Motil (2013) 25, 208–221
  32. 32. Vagus Nerve: A Structural Link? › Vagal function is associated with: - psychological resilience - psychophysiological flexibility & response to environmental challenge - emotion capacity & social engagement - glucose regulation - inhibition of hypothalamic-pituitary-adrenal (HPA) axis - regulation of immune function › Chronic decreases reflect impairment of the cholinergic anti-inflammatory reflex  - immune dysfunction and inflammation  - CVD, diabetes, osteoporosis, arthritis, Alzheimer's disease, periodontal disease, and certain types of cancers as well as declines in muscle strength and increased frailty and disability Kemp & Quintana, 2013; Thayer & Sternberg, 2006; Thayer et al., 2010; Kashdan & Rottenberg, 2010; Porges (2011); Tracey (2002)
  33. 33. Heart Rate Variability (HRV) • HRV relates to analyses on the R – R interval • QRS complex – ventricle depolarization • T wave – ventricle repolarization • P wave – depolarisation of the atria prior to contraction Mechanical events of the cardiac cycle lag slightly behind the electrical signals; thus, the contraction of the cardiac muscle comes just after the corresponding electrical signal
  34. 34. HRV: Time domain  Measures the temporal variation between heart beats (i.e., R-R waves)  Common measures include:  Standard deviation of normal to normal (or N-N) intervals (SDNN)  Root mean square successive differences (RMSSD): mediated by the PNS Kleiger, R., Stein, P., & Bigger, J. (2005). Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc, 10(1); Appelhans & Luecken, 2006
  35. 35.  Frequency domain: decomposes HRV signal into magnitude & frequency of multiple sinusoidal waves  A Fast Fourier transform (FFT) transforms the signal from time- to frequency-domain  High frequency (HF) power: reflects cardiac parasympathetic influence due to respiratory sinus arrhythmia  Low frequency (LF) power reflects baroreflex function, a homeostatic mechanism for maintaining blood pressure HRV: Frequency domain Saul, 1990; Kleiger, R., Stein, P., & Bigger, J. (2005); Goldstein, Bentho, Park & Sharabi, 2011; Appelhans & Luecken, 2006
  36. 36. Impact of Anxious Anticipation vs Slow Breathing Ruth Wells, 2011, Honors student. Kemp & colleagues, 2012. Matter Over Mind: A Randomised-Controlled Trial of Single-Session Biofeedback Training on Performance Anxiety and Heart Rate Variability in Musicians. PLoS ONE 7(10): e46597. doi:10.1371/journal.pone.0046597
  37. 37.  Provides additional information to more traditional measures, e.g.  Poincaré plot  Measures the complexity and predictability of heartbeats  less linearity – more variability HRV: Non-linear Domain Fig: The Poincaré graph plots each R-R interval as a function of the next R-R interval Kleiger, R., Stein, P., & Bigger, J. (2005). Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc, 10(1)
  38. 38. HRV Poincaré graph: Impact of age Healthy, young participant Older participant with CVD Lopes & White, book chapter
  39. 39. HRV & respiratory sinus arrhythmia  HR decelerates with expiration & accelerates with inspiration  Phasic changes in HRV: increases when calm, and decreases with stress  Resting state HRV: a marker of mental & physical health
  40. 40. Impact of Intensive 10-day Meditation Course Jonathan Krygier, 2011- present, PhD student. Kemp & colleagues, 2013. Int J Psychophysiol 40
  41. 41. HRV biofeedback & Performance Anxiety in Musicians Ruth Wells, Honours student, 2011; Kemp & colleagues, 2012. PLOS ONE
  42. 42. HRV biofeedback & anxious anticipation Impact of breathing intervention on RR intervals: Normal breathing during anticipation stress (left fig; 12 breaths/min) vs HRV biofeedback (right fig; 6 breaths/min) Experimental induction of performance anxiety (anxious anticipation) in professional musicians Ruth Wells, Honours student, 2011; Kemp & colleagues, 2012. PLOS ONE
  43. 43. Anxiety Decreased & HRV increased in Intervention Group Ruth Wells, Honours student, 2011; Kemp & colleagues, 2012. PLOS ONE 43
  44. 44. The traditional view of the autonomic nervous system • Two systems: • the sympathetic (red) • parasympathetic (blue) › 2 behavioural patterns: › ‘Fight or flight’: dependent on the SNS › ‘Rest & digest’: dependent on the PNS
  45. 45. Polyvagal Theory Porges (2011). The Polyvagal Theory Stephen Porges John Hughlings Jackson 1835-1911 Polyvagal Theory is a phylogenetically ordered, hierarchical model that draws on the Jacksonian principle of ‘dissolution’ John Hughlings Jackson (1858): ‘‘when the higher [phylogenetically newer neural circuits] are suddenly rendered functionless, the lower rise in activity’’
  46. 46. Polyvagal Theory: Implications for Emotion Porges (2011). The Polyvagal Theory Myelinated vagus: originates from nucleus ambiguus; supports social communication & psychophysiological flexibility; activity explicitly linked to HRV Sympathetic nervous system: supports mobilisation behaviours, e.g. fight, fight, play Unmyelinated vagus: dorsal vagal complex; most phylogenetically primitive; responsible for immobilisation behaviours, e.g. extreme terror, bradycardia, vasovagal syncope, reproduction, nursing, pair-bonding
  47. 47. HRV & Oxytocin • Oxytocin (OT) plays a key regulatory role in social behaviour • We examined the impact of OT on resting-state HRV, an index of motivation & capacity for social behaviour • Standard dose of 24 intranasal units (IU) (3 puffs per nostril, each puff containing 4 IU) of either OT or placebo • OT increases HRV, larges using the DFA non-linear measure of HRV • DFA decreases  more random Kemp et al. (2012). PLOS ONE signal
  48. 48. Heart Rate, HRV & Stress  Heart rate and it’s variability is very sensitive to stress  Under resting state: large beat to beat variability  Stress condition: decreases HRV (& HR increase) Rest Stress: Task instructions followed by task (serial 13’s task with social pressure) Sasha Saunders, Honours student, 2011
  49. 49. Heart Rate, HRV, Stress & Escitalopram - Single dose escitalopram (20mg) 49 - N=44, healthy females, cross-over design Under Stress: - HR increased - HRV (HF nu; 0.15-0.4Hz) decreased - large effect sizes observed Under Treatment: - HR decreased - HRV (HF nu; 0.15-0.4Hz) increased - large effect sizes observed Sasha Saunders, Honours student, 2011, Kemp & colleagues, 2013, Psychopharm, Dec 15. [Epub ahead of print]
  50. 50. Interaction with Age 50 Findings - Effects found to be specific to those >25yrs - No beneficial cardiac effects for those <25yrs Interpretation? - Black box warnings for young adults - Maturational differences in PFC Framework - Theoretical framework for understanding treatment-emergent suicidality was proposed Sasha Saunders, Honours student, 2011, Kemp & colleagues, 2013, Psychopharm, Dec 15. [Epub ahead of print]
  51. 51. HRV & emotion recognition Daniel Quintana, 2010-2013, PhD Student. Kemp & colleagues, 2012. International Journal of Psychophysiology
  52. 52. HRV is reduced in depression Kemp et al.., 2010, 2011, 2012.. Biological Psychiatry. Hedges's g and 95% CI p-Value 0.312 0.340 0.001 0.124 1.000 0.040 0.744 0.009 1.000 0.869 0.607 0.828 0.686 0.731 0.027 -2.00 -1.00 0.00 1.00 2.00 Reduced HRV Increased HRV frequency HRV Reduced HRV Unmedicated depressed patients without CVD display reduced HRV (relative to controls) Small effect size of HRV in time & frequency domain (Hedges g: ~0.3) Large effect size of HRV in non-linear domain (Hedges g: 1.9)
  53. 53. Reduced HRV is a trait marker of depression Brunoni, Kemp, et al. (2013). The International Journal of Neuropsychopharmacology
  54. 54. Depression & anxiety comorbidity Method: Case-control Sample: CTLS: n=94 MDD alone: n=24 MDD+PD/PTSD: n=14 MDD+GAD: n=24 › Major depressive disorder (MDD) with generalised anxiety disorder (GAD) display greatest reductions in HRV relative to CTLS › Findings were NOT able to be explained by increased depression severity Kemp et al.., 2012. PLoS ONE.
  55. 55. HRV & Generalised Anxiety Disorder MDD with GAD Worry & hyper – vigilance Unable to disengage threat detection Chronic withdrawal of PNS long term reductions in HRV Increased risk for CVD & SCD Kemp et al.., 2012. PLoS ONE.
  56. 56. Impact of past anxiety disorder Past – but not current anxiety – adversely impacts HRV › Method: case – control › Sample: Women with hx of anxiety (n=22) versus women w/out (n=34) › Resting state HRV is reduced in mothers with hx of anxiety disorder in first trimester Braeken, Van Den Bergh, Kemp, PLOS ONE, 2013
  57. 57. › Method: case – control › Sample: Infants of women with past anxiety (n=16) versus infants of women w/out (n=28) › History of maternal psychopathology impacts on HRV in mother and infant › Implications: reduced HRV in infants may predispose them to future psychiatric illness & reduced longevity RMSSD Child Healthy Lifetime Anxiety 4 3 2 1 0 Healthy p=.048, Hg=.63 Lifetime Anxiety RMSSD Child Impact of past anxiety disorder on offspring Braeken, Van Den Bergh, Kemp, PLOS ONE, 2013
  58. 58. What is the impact of antidepressants on HRV? No difference with SSRIs Increased HRV with rTMS Reduced HRV with TCAs No difference in HRV Kemp et al.., 2010. Biological Psychiatry. Method: Meta-analysis Sample: N=186
  59. 59. No impact of tDCS or sertraline on HRV… even in treatment responders! Brunoni, Kemp, et al. (2013). The International Journal of Neuropsychopharmacology
  60. 60. Longitudinal findings (2-yrs): all classes of a/deps affect HRV › 2-year changes in HRV in different antidepressant groupings › respiratory sinus arrhythmia (RSA) = measure of HRV › All classes of antidepressants adversely affect HRV › TCA > SNRI > SSRI Epidemiological findings: TCAs increase risk of CVD over 8 yrs by 35%. Other findings indicate that antidepressant use (inc SSRI) increases risk of SCD 3.34-fold. Licht et al.., 2011. Biological Psychiatry; Hamer et al., 2010. Eur Heart J; Whang et al., 2009. JACC
  61. 61. Cholinergic Anti-Inflammatory Reflex Vagal function plays critical role in inflammation (hence CAR) Nicotinic acetylcholine receptor α7 subunit is an essential regulator of inflammation Dysregulation  excess of cytokines, impaired fasting glucose & HPA-axis dysregulation (neurosurgeon) Kevin Tracey & colleagues, 2002 – 2012; Wang et al. 2003. Nature; Thayer & Sternberg, 2010
  62. 62. Thayer & Sternberg, 2010
  63. 63. HRV & components of the metabolic syndrome › N=228, participants aged 18 – 21yrs › SBP, hs-CRP associated with decreases HRV › MVPA associated with increases WC: waist circumference in HRV MVPA: moderate-to-vigorous physical activity SBP: systolic blood pressure Trg: triglycerides Glu: glucose HDL: high-density lipoprotein hs-CRP: C-reactive protein Soares-Miranda et al., 2012. Diabetes Metab Res Rev
  64. 64. Cortical structures Amygdala Nucleus Ambiguus Vagus Decreased HRV Nucleus Tractus Solitarius Increased HRV Response to environmental challenge Nucleus Tractus Solitarius Social behaviour Chronic reductions in HRV Chronic elevation in HRV Psychophysiological rigidity Psychophysiological flexibility Morbidity, mortality Health, longevity Phasic change: normal response to environment Chronic change: implications for mortality / longevity
  65. 65. Vagal nerve function Behavioural response strategies Emotion Psychophysiological flexibility Control of inflammatory Psychiatric Illness Resilience Wellbeing processes Physical disease Mortality Longevity Vagal nerve dysfunction, psychiatric illness, ill-health Healthy vagal nerve function, well-being, longevity
  66. 66. Call for Contributions http://www.frontiersin.org/emotion_science/researchtopics/mechanisms_underpinning_the_li/2668
  67. 67. Acknowledgements & Thanks Dan Quintana PhD Student, 2010-2013 Prof Gin Malhi University of Sydney Prof Richard Bryant University of NSW Prof Paulo Lotufo USP A/Prof Isabela Benseñor USP Dr Andre Brunoni USP Prof Bea Van Den Bergh Tilburg University Ruth Wells Honors Student, 2011 Jonathan Krygier PhD Student, 2011-
  68. 68. Acknowledgements Paulo Lotufo Isabela Benseñor Andre Brunoni … and the team at Centro de Pesquisa Clinica e Epdemiológica

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