bridging the gap between emotion and health

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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

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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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Page 1: Bridging the gap between emotion and health

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  

Page 2: Bridging the gap between emotion and health

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

Page 3: Bridging the gap between emotion and health

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

3

http://shambhalatimes.org/2011/10/20/before-and-after-portraits-from-dathun/

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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

Page 10: Bridging the gap between emotion and health

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

Page 11: Bridging the gap between emotion and health

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

Page 12: Bridging the gap between emotion and health

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.

Page 13: Bridging the gap between emotion and health

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)

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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

Page 15: Bridging the gap between emotion and health

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

Page 16: Bridging the gap between emotion and health

The Emotional Brain

Page 17: Bridging the gap between emotion and health

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

Page 18: Bridging the gap between emotion and health

Paul Ekman’s 6 Basic Emotions

Anger Disgust Fear Happiness Sadness Surprise

Carroll Izard: distinct emotions appear within the first months of life

Page 19: Bridging the gap between emotion and health

Emotions as ‘Natural Kinds’

From: Lindquist et al., 2013

Fear: amygdala

Disgust: insula

Anger: OFC

Sadness: ACC

Page 20: Bridging the gap between emotion and health

But are emotions a construct of social reality?

Ref: Barrett, 2012

What emotion is expressed here?

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Ref: Barrett, 2012

And now?

Social reality?

Page 22: Bridging the gap between emotion and health

Emotions as Psychological Constructions

From: Lindquist et al., 2013

Emotion are made up of elements:Core affectConceptualisationLanguageExecutive attention

Page 23: Bridging the gap between emotion and health

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.”

Page 24: Bridging the gap between emotion and health

William James on Emotion (1884)

“Does your heart pound because you are afraid... Or are you afraid because you feel your heart pounding?”

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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.

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Culturally universal categorical somatotopic maps

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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

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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)

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The Vagus Nerve

Bonaz et al., Neurogastroenterol Motil (2013) 25, 208–221

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› 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?

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• 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)

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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

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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

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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

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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

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HRV Poincare graph: Impact of age

Healthy, young participant Older participant with CVD

Lopes & White, book chapter

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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

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HRV biofeedback & Performance Anxiety in Musicians

Ruth Wells, Honours student, 2011; Kemp & colleagues, 2012. PLOS ONE

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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

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Anxiety Decreased & HRV increased in Intervention Group

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Ruth Wells, Honours student, 2011; Kemp & colleagues, 2012. PLOS ONE

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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

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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’’

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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

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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

Page 48: Bridging the gap between emotion and health

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)

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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

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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]

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HRV & emotion recognition

Daniel Quintana, 2010-2013, PhD Student. Kemp & colleagues, 2012. International Journal of Psychophysiology

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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)

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Reduced HRV is a trait marker of depression

Brunoni, Kemp, et al. (2013). The International Journal of Neuropsychopharmacology

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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

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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.

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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

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› 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

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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

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No impact of tDCS or sertraline on HRV… even in treatment responders!

Brunoni, Kemp, et al. (2013). The International Journal of Neuropsychopharmacology

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› 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

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(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

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Thayer & Sternberg, 2010

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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

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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

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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

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Call for Contributions

http://www.frontiersin.org/emotion_science/researchtopics/mechanisms_underpinning_the_li/2668

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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-

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Acknowledgements

Paulo Lotufo Isabela Benseñor Andre Brunoni

… and the team at Centro de Pesquisa Clinica e Epdemiológica PERGUNTAS?