the science of the good life: unraveling the …...the science of the good life: unraveling the...

The Science of the Good Life:

Unraveling the Complexity of Well-being

C. Robert Cloninger, MD, PhD

Washington University in St. Louis

East-West Connections,

Culture, Cognition, & the Good Life

Singapore, September 2015

What is Health ? – WHO Definition

A state of physical, mental, social / spiritual well-being in which the developing person

– Realizes and uses his or her own abilities

– Can cope with the normal stresses of life

– Learns to work productively and fruitfully

– Learns to contribute to his or her community

Indivisible from physical health

More than the absence of disease

WHO 1946; Herrman H et al (2005)

What is Well-Being?

“Well-Being is a contented state of being healthy, happy, & prosperous;

welfare” (American Heritage Dictionary, 4th ed, 2000)

Types or Components of Well-Being

• Hedonic Well-Being – feeling good (deriving pleasure and happiness from

life)

• Eudaimonia – doing good ( mature and actively virtuous living)

• Wellness – living long ( physical health, absence of disease or infirmity)

• Prosperity – flourishing (success, good fortune, fulfillment, satisfaction)

“Ill-Being is the absence of health, happiness, or prosperity”

• Inactive or physically disabled

• Unhappy or dissatisfied

• Socially isolated or alienated

• Unsuccessful or unfulfilled (not thriving)

How is Well-Being measured?

Physical Vitality: physical fitness, high levels of energy, number of

days we feel full of vitality, resilience, plasticity, absence of chronic

or life-threatening diseases, as in CDC’s PH-Well-being scale

Healthy Thoughts– Emotions : more positive than negative emotions, as measured by

Watson’s PANAS

– Personality: maturity and integration of character traits, as measured by

Temperament and Character Inventory (TCI), Ryff’s psychological WB

scale, or maturity of defense mechanisms

– Satisfaction with life: reliable subjective ratings, like Diener’s measure

Virtues: self-transcendent values and character traits like courage,

trust, justice, moderation, honor, wisdom, patience, love, hope, and

faith, as in Schwartz’s Values Survey or Petersen and Seligman’s

Values in Action Inventory

The Psychobiological Model of Personality (Cloninger 2014)

IDENTITY

Key Fact Usually Ignored in Developing a Personality Model

Human Beings have three major systems of learning and memory, as a result of their long evolutionary development on way to self-awareness

1. Habits and Skills – procedural learning

1. Facts and Propositions – semantic learning of words and beliefs

1. Intuitions and Narratives – self-aware consciousness as expressed in autobiography and studies of personal and social movements

January 2012

Distinct Qualities of 3 Systems

Habits

– quantitative strength of associations, deterministic, prelogical, subjectively linked with basic emotions,not rational, not self-aware

Propositions

– Contingently logical, hierarchical, algorithmic (predictable),subjectively linked with secondary emotions, rational, not self-aware

Personal Episodes in life narrative

– intuitive, interdependently modular & episodic, holographic (parts elicit wholes), creative (original, not algorithmic), rational, self-aware

Cloninger, Feeling Good: The Science of Well-Being, 2004January 2012

Cycle of Reciprocal Interactions – Personality

Identity

CharacterTemperamentmeaning

salience

unconscious

impulse

conscious

analysis

contemplation

acceptance

commitment

humor

appreciation

engagement

automatic self-aware thought

Personality is a dynamic system with self-directed emergent properties.

Effects are simultaneously top-down and bottom-up, so it must be

studied as a whole with nested networks of interactive relationships.

Properties of Complex Adaptive Systems

Holism – system cannot be reduced to separate parts because it depends

on relationships and feedback among components

Indeterminism – outcomes are predictable probabilistically

Non-linear dynamic relationships

• Saltatory change (stage-like shifts) - Small shifts at tipping points provoke

sudden marked changes with

• Multi-finality – same profile can have multiple clinical outcomes

• Equi-finality – different profiles can lead to the same clinical outcome

Coactive change – behavior emerges co-actively from bottom-up and top-

down simultaneously (person-centered management)

Focus on adaptive variation and local initiative

Self-similarity – parts are like the whole (like fractals, or persons being a

microcosm embedded in a self-similar macrocosm

The Dynamics of Well-Being

Enlarging Consciousness

Creative Life Project

Outlook of Unity

Outlook of Separateness

Ternary Processes of Developing Personality (1)

Identity

CharacterTemperament

meaning

salience

unconscious

impulseconscious

analysis

contemplation

acceptance

commitment

humor

appreciation

engagement


Ternary Processes of Developing Personality (2)

Identity

CharacterTemperament

meaning

salience

unconscious

impulseconscious

analysis

Who am I?

What makes me happy?

What gives meaning?

Hope

Love

Work


Interaction of Harm Avoidance & Novelty Seeking

• nH• nh

• NH• Nh

Impulsive

Extraverted

Neurotic

Distressed

Introverted

Rigid

Cheerful

Stable

High Novelty Seeking

Low Novelty Seeking

High Harm AvoidanceLow Harm Avoidance

January 2012

Interaction of Harm Avoidance & Reward Dependence

• rH• rh

• RH• Rh

Friendly

Sociable

Avoidant

Dependent

Aloof

Distant

Oppositional

Defiant

High Reward Dependence

Low Reward Dependence

High Harm AvoidanceLow Harm Avoidance

January 2012

Interaction of Reward Dependence & Novelty Seeking

• nR• nr

• NR• Nr

Independent

Eccentric

Attention-Seeking

Traditional

Dependable

Privacy-Seeking

High Novelty Seeking

Low Novelty Seeking

High Reward

DependenceLow Reward

Dependence

January 2012

Brain Structure and Function in Harm Avoidance

Structure/Function

Variable

Observed Effect Reference

Amygdala activation &

connectivity with

subgenual Cingulate and

with mPFC

Increased sensitivity to

fearful stimuli mediated by

activation of amygdala &

connectivity with

perigenual cingulate and

with medial PFC

Pezawas et al, 2005

Yang et al, 2009

Baeken et al, 2014

Van Schuerbeek et al,

2014

Insular Salience Network Increased connectivity of

right Anterior insula with

ACC and with DLPFC

Paulus et al, 2003

Markett et al, 2013

Volume of Anterior

Cingulate Cortex

Increased volume of right

right ACC, smaller of left

Pujol et al, 2002

Van Schuerbeek et al,

2011

Volume of Cerebellar

white matter & Cortex

Smaller volume bilaterally Laricchiuta et al, Hum

Brain Mapp 2014

Mean Diffusivity of

Striatum

Increased in pallidum

bilaterally

Laricchiuta et al, Brain

Struct Funct 2014January 2012

Brain Structure and Function in Novelty Seeking

Structure/Function

Variable


Connectivity of ventral

striatum

Greater connectivity with

hippocampus, amygdala,

and OFC, activated by

novel stimuli

Naghavi et al, 2009

Lei X, Chen C, et al, 2014

Cohen MX et al, 2009

Insular Salience Network Reduced activity with

higher NS

Enzi B, et al, 2009

Kyeong et al, 2014

Ventral Striatal Dopamine

Synthesis Capacity

Greater synthesis

capacity if high NS

controlling for age, HA (r=

.8)

Lawrence & Brooks 2014

Midbrain dopamine

autoreceptor availability

Reduced availability if

high NS and more rapidly

sensitized by stimulants

Zaid et al, 2008

Boileau et al, 2006

Cortical Volumes Greater left posterior

cingulate gray matter and

smaller inferior frontal

gray matter volumes

Gardini, Cloninger, Venneri,

2009;

Van Schuerbeek et al, 2011January 2012

Brain Structure & Function in Reward Dependence

Structure/Function

Variable


Cortico-striatal System Greater GMV and

connectivity of striatum

(caudate) with OFC and

Temporal lobes

Gardini. et al, 2009

Lebreton et al, 2009

Cohen et al, 2009

Lei et al, 2014

Caudate Volume/Activity Greater size and activity Hakamata et al, 2006

Lidaka et al, 2006

Oxytocinergic System Larger oxytocinergic

hypothalamus regions with

reduced connectivity to

amygdala, septum, dorsal

ACC, activated by

perceptual processing of

facial emotions and social

cues

Tost et al, 2010

Striatal Opioid Availability Greater Opioid receptor

availability in ventral

striatum bilaterally

Schreckenbrger et al, 2008

January 2012

The Temperament Cube (Cloninger 1987)

January 2012

Higher Cognitive Functions: Mental Self-Government

Executive Functions (Self-directedness)

– Resourceful, purposeful, self-accepting, responsible,

– self-actualizing

Legislative Functions (Cooperativeness)

– Tolerant, helpful, empathic, principled,

– compassionate

Judicial Functions (Self-transcendence)

– Idealistic, self-forgetful, joyful, contemplative,

– spiritual

Brain Structure and Function for Character

Self-directedness is characterized by self-reflection on internal cues,

activating a neural circuit including the anterior cingulate cortex, the

posterior cingulate cortex, and the medial frontal cortex, and less

consistently the temporal cortex for the appraisal of the self (Ochsner et

al, 2005; van der Meer et al, 2012), as demonstrated for Self-directedness

(van Schuerbeek et al, 2011).

Cooperativeness is characterized by empathy and meta-cognition

(mentalizing). It is correlated with white matter volume in the medial

frontal and precentral gyrus and with gray matter volume in the superior

temporal gyrus (BA22) (Van Schuerbeek et al, 2011).

Self-Transcendence is characterized by a holistic perspective in which a

person identifies him or herself as participating in something greater,

leading to altruistic, transpersonal, and spiritual experiences. ST is

correlated with greater GMV in regions of the autobiographical memory

system including the middle temporal gyrus (BA 21)(Kaasinen et al, 2005;

Van Schuerbeek, 2011), inferior parietal gyrus (BA40) and lesser GMV in

the superior frontal gyrus in medial PFC (BA 10) (Van Schuerbeek, 2011).January 2012

The Character Cube

PA and NA are differentially correlated with character

PA and NA are NOT

correlated

All possible combinations

of high and low scores

are observed in different

personality types

Composite Indices of

“Affect Balance” can be

composed as the

difference between PA

and NA

0

5

10

15

20

25

30

35

40

sc

t

sc

T

sC

T

sC

t

--- Sc

t

Sc

T

SC

t

SC

T

Sadness

Happiness

Cloninger 2004

Emotional, Physical, and Social Well-being depend on Character Profiles

Cloninger & Zohar, JAD 2011

The components of Self-Transcendence

– Joyfulness is the emotional component of TCI Self-transcendence

– Joy is one component of a set of closely intertwined character traits

• Idealistic:

– “I would suffer for the sake of what is right in order to be true to my ideals”

– “The moral ideals within me fill my heart with awe and admiration.”

• Self-forgetful, intuitive:

– “Often when I am concentrating on something, I lose awareness of the

passage of time”

– “Often I have unexpected flashes of insight or understanding while

relaxing”

• Contemplative:

– “I am grateful for supernatural guidance”

– “When I am in deep contemplation or prayer, I sometimes feel that I am

directly connected to a supernatural source of love and peace.”

• Religious vs rationalistic

– “Religious experiences have helped me understand the real purpose of

my life”

Validation of ST measures by Objective Measurement

Higher ST x SD is associated with health and longevity, indicated by

DHEA/cortisol ratio and cardiovascular fitness

Higher STxSDxCO is associated with better Heart Rate Variability or

vagal tone in 24-hour recordings of heart rhythms (Zohar et al, 2013)

Higher ST is associated with activation of the brain’s autobiographical

memory system, leading to greater creativity, capacity to develop a

meaningful life narrative, and to face adversity and ultimate situations

without a sense of hopelessness or foreshortened future (Cloninger 2004)

Genome-wide association studies show that both temperament and

character are equally heritable with complex genetic influences but

character is more socioculturally malleable – temperament is moderately

stable throughout life, but character develops in the direction favored by

social norms (Josefsson et al, 2013; Cloninger et al, GWAS in progress)

Ten-year prospective study of TCI personality change

Cardiovascular Risk in Young Finns Study (Liisa Keltikangas Jarvinen,

Psychology PI) with 3560 people in 6 birth cohorts aged 3 to 18 at

baseline in 1980

TCI administered in 1997, 2001, and 2007

Cohorts in 1997 were aged 20, 23, 26, 29, 32, and 35

So observed intervals of change extend from 20 to 45 years

Complete TCI data in all years on 1314 subjects (858 women and 456

men)

January 2012

Individual reliable change in TCI traits 1997-2001

TCI Trait Decrease % No change % Increase %

Novelty Seeking 6.8 88.7 4.5

Harm Avoidance 11.9 78.9 9.2

Reward Dependence 2.1 92.6 5.3

Persistence 2.3 94.7 3.0

Self-directedness 4.0 79.3 16.7

Cooperativeness 7.4 76.9 15.7

Self-Transcendence 16.1 78.6 5.3

N = 1314, change based on reliable change index

Kim Josefsson et al., in review 2011January 2012

Average Harm Avoidance levels, ages 20-45 years

2.300

2.400

2.500

2.600

2.700

2.800

2.900

20-24 25-29 30-34 35-39 40-45

Mean

-sco

re

Agegroup

Harm Avoidance, d = - 0.01 / 5 years

January 2012

Average Novelty Seeking levels, ages 20-45 years

2.700

2.800

2.900

3.000

3.100

3.200

3.300

20-24 25-29 30-34 35-39 40-45

Mean

-sco

re

Agegroup

Novelty Seeking, d= - 0.10 / 5 years

January 2012

Average Reward Dependence levels, ages 20-45 years

3.000

3.100

3.200

3.300

3.400

3.500

3.600

20-24 25-29 30-34 35-39 40-45

Mean

-sco

re

Agegroup

Reward Dependence, d = - 0.03 / 5 years

January 2012

Average Persistence levels, ages 20-45 years

2.900

3.000

3.100

3.200

3.300

3.400

3.500

20-24 25-29 30-34 35-39 40-45

Mean

-sco

re

Agegroup

Persistence, d=0.06 / 5 years

January 2012

Average Self-directedness levels, ages 20-45 years

3.300

3.400

3.500

3.600

3.700

3.800

3.900

20-24 25-29 30-34 35-39

Mean

-sco

re

Agegroup

Self-directedness, d=0.23 / 5 years

January 2012

Rational Intuition (SDxST) Predicts Objective Health

-0.25

-0.2

-0.15

-0.1

-0.05

0

0.05

0.1

0.15

0.2

0.25

sd_STSD_ST

Cortisol

DHEAS_Cortisol

METS

BloodAbnormality

Metabolic

abnormalities

271 adults 40+ years old, Israel (Dahan, Zohar, Cloninger, Hirschmann, 2012)

Ln(LF/HF) is a measure of ANS ambulatory recording

balance between Sympathetic (LF) and Parasympathetic

(HF) activity.

Positive emotions such as appreciation increase HRV and

vagal tone .

Why is heart rate variable?

because of sympathetic and parasympathetic inputs, which are regulated by character traits

McCraty et al, 2004Zohar A et al, Personality & HRV, 2013

Engagement or Improvisation activate Anterior PFC

When making charitable

donations, “pleasurable

engagement” was correlated 0.87

with activation of the anterior

prefrontal cortex (frontal poles

and medial frontal gyrus- BA

10/11/32 – see pole of purple

region of figure) [Moll J et al,

PNAS 2006]

Anterior prefrontal cortex also

activated by spontaneous multi-

tasking, exploring new choices

that are not exploitative, or

creative improvisation of music in

self-awareness [Cloninger

2004,Daw et al 2006; Limb &

Braun 2008]

Fundamental Principles

A person is the whole human being with three components –

body, thoughts, and soul

Health is a complete state of physical, mental, social and

spiritual well-being

Physical, mental, social and spiritual well-being are

inseparable

Physical, mental, social and spiritual functioning all contribute

to the causes and development of either

joyful well-being or miserable ill-being

Joyful Well-Being depends on combining 3 life functions

The 3 principles of being joyful:

1. Working in service of others

• Enjoy giving of yourself• Be kind and loving

2. Letting go

• Enjoy acceptance withoutfighting or worry

• Be generous & hopeful

3. Growing in awareness

• Enjoy learning and adaptung constantly

• Be humble and faithful Diver of Paestum

The Virtuous Circle leading to Joyful Well-Being

Virtue

PlasticityFunctioning

Outlook of Unity

CR Cloninger & KM Cloninger 2011

Motor

Of

Well-Being

© Anthropedia

Anthropedia projects promoting Joyful Well-being

Thoughts are addressed through

– cognitive-behavioral approaches

– Silence of Mind meditation addresses each of 3 steps in

thought – relaxing the emotional brain, promoting

mindfulness, facilitating contemplation (listening to the

psyche)

Body is addressed through

– Nutrition, exercise, sleep hygiene, elevating rituals

– Coordination and dance exercises that promote plasticity

and letting go

Psyche (Soul) is addressed through

– Contemplation (listening to psyche/soul)

– Non-verbal forms of prayer and meditation

Cross-cultural data of TCI-R

26 countries

< 28.000 subjects

Cross-cultural data of TCI-R and TCI

33 countries

Trait of

Interest

Study

(Site)

Subject

Numbers

SNP Platform Clinical

Assessment

Schizophrenias MGS

(USA/Aus)

4196 cases

3825 controls

Affymetrix 6.0 DIGS

PIS (Portugal) 346 cases

215 controls

Affymetrix 5.0 DIGS

CATIE (USA) 1460 cases

733 controls

Affymetrix

500K +

Perlegen

164K

PANSS

QOLQ

SKID-IV

Personality &

Well-being

YFS

(Healthy

Finns)

2620 Illumina 670K

custom chip

TCI (Likert)

HTS (Healthy

Koreans)

1400 Affymetrix 6.0

Illumina 350K

TCI (true-

false)

HSS (Healthy

Germans)

1000 Affymetrix 6.0

Illumina Quad

TCI-R (Likert)

Genomic Study of Personality & Well-being Currently In Progress

SEARCHING FOR THE CAUSES OF COMPLEX DISEASES

… fuzziness hides our targets

… we have been searching for clues “just where the light is shining”

… we have to perform a search from both the causes and the outcomes

simultaneously

UNCOVERING THE CAUSES OF COMPLEX DISEASES

PRECISION MEDICINE -- INTEGRATING CARE & RESEARCH

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Figure S7

THE HUMAN CELL – MICROCOSM OF LIFE

Conclusions

The path to well-being involves increasing Self-directedness,

Cooperativeness, and Self-transcendence in combination

(Cloninger & Zohar, 2010)

Effective therapeutic approaches for developing well-being all

work by activating a system of feedback interactions among

functioning, plasticity, and virtuous ways of thinking and

acting that promote health, happiness, and meaning

(Cloninger & Cloninger, 2011)

Therefore effective integrative treatment must address all

three aspects of the being – physical, mental, and spiritual

There is no one right approach – rather there are many

variations on what works for different people under different

circumstances, which encourages respect, freedom, and

tolerance for diversity

Any Questions or Comments/Discussion ?

?

Comparison of Complex and Deterministic Systems

Complex Adaptive Systems Deterministic Additive Systems

Holism Reductionism

Indeterminism Determinism

Non-linear Dynamic Relations Linear Relations

Focus on adaptive variation Focus on averages in groups

Local initiative Global control

Co-active change Top-down control

Self-similarity of functions of all

interactive components

Specialized functions by

separate parts

Metaphor of morphogenesis

(life-like evolution)

Metaphor of Assembly

(machine-like operation)

How are PA and NA measured by PANAS?

afraid, scared

nervous

distressed, upset

hostile, irritable

jittery

ashamed, guilty

(sad)

Interested, enthusiastic

alert, attentive

inspired, excited

strong, determined

active

proud

(happy)

Watson, Clark, Tellegen (1988)– rated 1 (slightly or not) to 5 (extremely)

Positive Affects Negative Affects

Limitations of Subjective Well-being measures

Subjective well-being measures are largely explained by one statement,

phrased in any of three ways

– “All things considered, I am happy.”

– “I am satisfied with my life?”

– “I am resilient.”

Popular psychological well-being and resilience measures are almost

entirely explained by high self-directedness, cooperativeness,

persistence, and low Harm Avoidance but not by self-transcendence (they

lack real spiritual content, even though satisfaction with spirituality is

empirically important too) (Bann et al, 2010; Eley, Cloninger, et al, PeerJ

2013)

Virtue measures need more validation (Cloninger & Cloninger, 2011)

In contrast, personality has been validated by self-report and observer

ratings, objective tests, and studied as a complex developmental process

Joyfulness measured as TCI Self-transcendence

“I have had moments of great joy in which I suddenly had a clear, deep

feeling of oneness with all that exists.”

“I often feel so connected to the people around me that it is like there is no

separation between us.”

“Sometimes I have felt like I was part of something with no limits or

boundaries in space and time.”

“I sometimes feel so connected to nature that everything seems to be part

of one living organism.”

Most people (59%) have experienced such oceanic feelings and/or

inseparability at some times in their life, but it is rare as a continuous

mode of being

Cloninger, The Science of Well-being, 2004

Exploring Your Personality and Lifestyle

Examines prior experiences with the major ingredients of lasting satisfaction

measurement of personality and emotionality – Temperament and Character Inventory (TCI) and measures of well-being

Explores how personality affects health, well-being, & quality of life

Explores Practices leading to well-being: – Letting Go– Working in Service of Others– Awareness

Suggests exercises to promote the experience of satisfaction, like acts of kindness

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