bridging the gap between emotion and health
DESCRIPTION
I gave this presentation to the Faculty of Medicine at the University of São Paulo in Ribeirão Preto, Brazil March 2014TRANSCRIPT
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: [email protected]; twitter: @andrewhkemp
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
The Devastating Impact of Mental Illness
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
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http://shambhalatimes.org/2011/10/20/before-and-after-portraits-from-dathun/
Before vs after 30 day meditation retreat
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Peter Seidler, Before and After Project, 2011
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Before vs after 30 day meditation retreat
Peter Seidler, Before and After Project, 2011
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Before vs after 30 day meditation retreat
Peter Seidler, Before and After Project, 2011
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Before vs after 30 day meditation retreat
Peter Seidler, Before and After Project, 2011
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Before vs after 30 day meditation retreat
Peter Seidler, Before and After Project, 2011
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Before vs after 30 day meditation retreat
Peter Seidler, Before and After Project, 2011
Medical consequences of Depression
10Gold & Chrousos, Molecular Psychiatry, 2002, 7: 254-75
Abnormalities
Typical symptoms (& more commonly researched)
Increasing knowledge on other abnormalities including autonomic function, metabolic syndrome & morbidity
Reduced Bone Density in Depression Osteoporosis
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Gold & Chrousos, Molecular Psychiatry, 2002, 7: 254-75
Trabeculations (spongy bone) are reduced
Cortical bone is also thinner
Coronary Heart Disease
Kemp & colleagues, under review
ELSA-Brasil is the first large multi-centre cohort study of adult health conducted inBrazil and is funded by its Ministries of Health, and Science and Technology.
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 factorsPenninx et al.., 2001. Arch Gen Psychiatry.
Without CVD (n=2397)
With CVD (n=450)
Psychological Distress Mortality
Russ et al., 2012, BMJ
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
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
The Emotional Brain
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
Ref: Darwin, 1872; Dalgleish, 2004
e.g. anger/aggression
- Frowning: protects eyes in anticipation of attack
Paul Ekman’s 6 Basic Emotions
Anger Disgust Fear Happiness Sadness Surprise
Carroll Izard: distinct emotions appear within the first months of life
Emotions as ‘Natural Kinds’
From: Lindquist et al., 2013
Fear: amygdala
Disgust: insula
Anger: OFC
Sadness: ACC
But are emotions a construct of social reality?
Ref: Barrett, 2012
What emotion is expressed here?
Ref: Barrett, 2012
And now?
Social reality?
Emotions as Psychological Constructions
From: Lindquist et al., 2013
Emotion are made up of elements:Core affectConceptualisationLanguageExecutive attention
The Emotional Brain
LeDoux, 1998, 2012; Lindquist et al., 2013
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.”
William James on Emotion (1884)
“Does your heart pound because you are afraid... Or are you afraid because you feel your heart pounding?”
Modern neuroscience is ‘neurocentric’
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“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.”
- 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
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Nummenmaa et al., 2013. PNAS.
Bodily Maps of Emotions
In five experiments, participants (n = 701) were shown two silhouettes of bodies alongside emotional words, stories, movies, or facial expressions.
Culturally universal categorical somatotopic maps
Neurovisceral Integration & Emotion
Thayer et al. (2009). Neurovisceral Integration Model Porges, 2011. The Polyvagal Theory
Nucleus Tractus Solitarius: a site of anatomical convergence of visceral inputs, which projects to regions contributing to coordinated autonomic, hormonal & immune output
Depression & CVD: Potential Mechanisms?
Musselman, D. L. et al. 1998. Archives of General Psychiatry; Nemeroff, C. B., & Goldschmidt-Clermont, P. J. 2012. Nat. Rev. Cardiol
› Increased HPA-axis activity
› Increased sympatho-adrenomedullary activity
› Increased inflammation
› Increased platelet activation and aggregation
› and reduced vagal function(heart rate variability, or HRV)
The Vagus Nerve
Bonaz et al., Neurogastroenterol Motil (2013) 25, 208–221
› 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)
Vagus Nerve: A Structural Link?
• 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
Heart Rate Variability (HRV)
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
HRV: Time domain
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
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
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
Provides additional information to more traditional measures, e.g. Poincare plot
Measures the complexity and predictability of heartbeats
less linearity – more variability
HRV: Non-linear Domain
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)
Fig: The Poincare graph plots each R-R interval as a function of the next R-R interval
HRV Poincare graph: Impact of age
Healthy, young participant Older participant with CVD
Lopes & White, book chapter
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
HRV & respiratory sinus arrhythmia
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Jonathan Krygier, 2011- present, PhD student. Kemp & colleagues, 2013. Int J Psychophysiol.
Impact of Intensive 10-day Meditation Course
HRV biofeedback & Performance Anxiety in Musicians
Ruth Wells, Honours student, 2011; Kemp & colleagues, 2012. PLOS ONE
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
Anxiety Decreased & HRV increased in Intervention Group
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Ruth Wells, Honours student, 2011; Kemp & colleagues, 2012. PLOS ONE
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
Polyvagal Theory
Porges (2011). The Polyvagal Theory
Stephen Porges John Hughlings Jackson1835-1911
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’’
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
Kemp et al. (2012). PLOS ONE
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 signal
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)
Sasha Saunders, Honours student, 2011
Rest Stress: Task instructions followed by task(serial 13’s task with social pressure)
Heart Rate, HRV, Stress & Escitalopram
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Sasha Saunders, Honours student, 2011, Kemp & colleagues, 2013, Psychopharm, Dec 15. [Epub ahead of print]
- N=44, healthy females, cross-over design- Single dose escitalopram (20mg)
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
Interaction with Age
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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]
HRV & emotion recognition
Daniel Quintana, 2010-2013, PhD Student. Kemp & colleagues, 2012. International Journal of Psychophysiology
HRV is reduced in depression
Kemp et al.., 2010, 2011, 2012.. Biological Psychiatry.
Study name Statistics for each study Hedges's g and 95% CI
Hedges's Lower Upper g limit limit p-Value
Agelink et al., 2001 -0.239 -0.703 0.224 0.312Agelink et al., 2002 (sample 1) -0.265 -0.809 0.279 0.340Agelink et al, 2002 (sample 2) -0.928 -1.490 -0.367 0.001Volkers et al., 2003 -0.324 -0.736 0.089 0.124Yeragani et al., 2002 0.000 -0.681 0.681 1.000Thayer et al., 1998 (sample 1) 1.128 0.053 2.204 0.040Thayer et al., 1998 (sample 2) -0.177 -1.239 0.885 0.744Udupa et al., 2007 -0.591 -1.034 -0.147 0.009Tulen et al., 1996 0.000 -0.434 0.434 1.000Lehofer et al., 1997 -0.048 -0.616 0.520 0.869Moser et al., 1996 -0.141 -0.677 0.395 0.607Tulen et al., 1996 (sample 1) -0.096 -0.956 0.765 0.828Tulen et al., 1996 (sample 2) -0.190 -1.109 0.729 0.686Dawood et al., 2007 0.111 -0.521 0.743 0.731
-0.210 -0.396 -0.024 0.027
-2.00 -1.00 0.00 1.00 2.00
Reduced HRV Increased HRV
High 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)
Reduced HRV is a trait marker of depression
Brunoni, Kemp, et al. (2013). The International Journal of Neuropsychopharmacology
Depression & anxiety comorbidity
› 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.
Method: Case-control Sample:CTLS: n=94MDD alone: n=24MDD+PD/PTSD: n=14MDD+GAD: n=24
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.
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
Impact of past anxiety disorder
Braeken, Van Den Bergh, Kemp, PLOS ONE, 2013
› 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
0
1
2
3
4HealthyLifetime Anxietyp=.048, Hg=.63
RM
SS
D C
hild
Impact of past anxiety disorder on offspring
Braeken, Van Den Bergh, Kemp, PLOS ONE, 2013
No difference in HRV
No difference with SSRIs
Reduced HRV with TCAs
Increased HRV with rTMS
What is the impact of antidepressants on HRV?
Kemp et al.., 2010. Biological Psychiatry.
Method: Meta-analysisSample: N=186
No impact of tDCS or sertraline on HRV… even in treatment responders!
Brunoni, Kemp, et al. (2013). The International Journal of Neuropsychopharmacology
› 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
Licht et al.., 2011. Biological Psychiatry; Hamer et al., 2010. Eur Heart J; Whang et al., 2009. JACC
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.
Longitudinal findings (2-yrs): all classes of a/deps affect HRV
(neurosurgeon) Kevin Tracey & colleagues, 2002 – 2012; Wang et al. 2003. Nature; Thayer & Sternberg, 2010
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
Cholinergic Anti-Inflammatory Reflex
Thayer & Sternberg, 2010
HRV & components of the metabolic syndrome
› N=228, participants aged 18 – 21yrs
› SBP, hs-CRP associated with decreases HRV
› MVPA associated with increases in HRVWC: waist circumference
MVPA: moderate-to-vigorous physical activity SBP: systolic blood pressureTrg: triglyceridesGlu: glucoseHDL: high-density lipoproteinhs-CRP: C-reactive protein
Soares-Miranda et al., 2012. Diabetes Metab Res Rev
Cortical structures
Amygdala
Nucleus Ambiguus
Vagus
Decreased HRV
Nucleus Tractus Solitarius
Increased HRV
Nucleus Tractus Solitarius
Response to environmental
challenge
Social behaviour
Morbidity, mortality Health, longevity
Chronic reductions in HRV Chronic elevation in HRV
Psychophysiological rigidity Psychophysiological flexibility
Phasic change: normal responseto environment
Chronic change: implications for mortality / longevity
Vagal nerve function
Psychophysiological flexibility
Psychiatric Illness
Wellbeing
Resilience
Physical disease
LongevityMortality
Behavioural response strategies
Emotion
Control of inflammatory processes
Vagal nerve dysfunction, psychiatric
illness, ill-health
Healthy vagal nerve function,
well-being, longevity
Call for Contributions
http://www.frontiersin.org/emotion_science/researchtopics/mechanisms_underpinning_the_li/2668
Acknowledgements & Thanks
Dan QuintanaPhD Student, 2010-2013
Prof Gin MalhiUniversity of Sydney
Prof Richard BryantUniversity of NSW
Prof Paulo LotufoUSP
A/Prof Isabela BenseñorUSP
Dr Andre BrunoniUSP
Prof Bea Van Den BerghTilburg University
Ruth WellsHonors Student, 2011
Jonathan KrygierPhD Student, 2011-
Acknowledgements
Paulo Lotufo Isabela Benseñor Andre Brunoni
… and the team at Centro de Pesquisa Clinica e Epdemiológica PERGUNTAS?