The Anatomy of Loneliness · 2008. 10. 30. · (e.g., CRP) Epinephrine Hypothalamus Pit....

The Anatomy of Loneliness

John T. CacioppoJohn T. CacioppoCenter for Cognitive and Social Neuroscience

Neuroscience InstitutePsychosocial

Stress

Central IL-1

ACTH

AdrenalGlands

Glucocorticoids

Epinephrine

Liver

IL-6IL-1ra

Systemic markers of inflammation

SNS

Vagus

Reticulo-endothelial

System (e.g., Spleen)

MIF

APPs(e.g., CRP)

Epinephrine

Hypothalamus

Pit.

Macrophages

IL-1ra

Leukocytes(e.g., Macrophages)

APPs,IL-1, IL-6

TNF-

IL-6

Glucocorticoids

Macrophages

CRH

Cornell University, October 2008

Central Dogma of Molecular Biologyg gy

DNAConstitution

Genome

RNA

Transcription

Genome

T i tRNA

Translation

Transcriptome

ProteinBrain

Proteome

Everything ElsePsychosocialStress

Central IL-1

ACTH

AdrenalGlands

Glucocorticoids

Epinephrine

Liver

IL-6IL-1ra


SNS

Vagus



MIF

APPs(e.g., CRP)

Epinephrine

Hypothalamus

Pit.

Macrophages

IL-1ra


APPs,IL-1, IL-6

TNF-

IL-6

Glucocorticoids

Macrophages

CRH

• Implication: Genes and biology (& brain) determine human thought & behavior

Metaphors for the Human MindHuman Mind

PsychosocialStress

Central IL-1

ACTH

AdrenalGlands

Glucocorticoids

Epinephrine

Liver

IL-6IL-1ra


SNS

Vagus



MIF

APPs(e.g., CRP)

Epinephrine

Hypothalamus

Pit.

Macrophages

IL-1ra


APPs,IL-1, IL-6

TNF-

IL-6

Glucocorticoids

Macrophages

CRH

Structure and Capabilities of a pConnected Collective

PsychosocialStress

Central IL-1

ACTH

AdrenalGlands

Glucocorticoids

Epinephrine

Liver

IL-6IL-1ra


SNS

Vagus



MIF

APPs(e.g., CRP)

Epinephrine

Hypothalamus

Pit.

Macrophages

IL-1ra


APPs,IL-1, IL-6

TNF-

IL-6

Glucocorticoids

Macrophages

CRH

PsychosocialStress

Central IL-1

ACTH

AdrenalGlands

Glucocorticoids

Epinephrine

Liver

IL-6IL-1ra


SNS

Vagus



MIF

APPs(e.g., CRP)

Epinephrine

Hypothalamus

Pit.

Macrophages

IL-1ra


APPs,IL-1, IL-6

TNF-

IL-6

Glucocorticoids

Macrophages

CRH

Demands of Social Living

• learning by social observation;

• recognizing the shifting status of friends and foes;

i i i d di i ff b• anticipating and coordinating efforts between two or more individuals;

• using language to communicate, reason, teach, and deceive others;

• orchestrating relationships, ranging from pair bonds and families to friends, bands, and coalitions;

• navigating complex social hierarchies, social norms and cultural developments;

• In anthropoid primates, mean social group size increases with relative neocortex volume (i d d th ti f• subjugating self‐interests to the interests of the pair

bond or social group in exchange for the possibility of long term benefits, which places a premium on capacities to self‐regulate;

(indexed as the ratio of neocortex volume to the volume of the rest of the brain). Solid circles, monkeys; open i l R i li

PsychosocialStress

Central IL-1

ACTH

AdrenalGlands

Glucocorticoids

Epinephrine

Liver

IL-6IL-1ra


SNS

Vagus



MIF

APPs(e.g., CRP)

Epinephrine

Hypothalamus

Pit.

Macrophages

IL-1ra


APPs,IL-1, IL-6

TNF-

IL-6

Glucocorticoids

Macrophages

CRH

• recruiting support to sanction individuals who violate group norms; and

• doing all this across time frames that stretch from the distant past to multiple possible futures.

circles, apes. Regression lines are reduced major axis fits. (Dunbar & Shutlz, 2007)

Neural Mechanism Promoting ParityNeural Mechanism Promoting Parity

Inferior frontal gyrusInferior parietal lobule

(Giacomo Rizzolatti et al. (1996). Premotor ( ( )cortex and the recognition of motor actions, Cognitive Brain Research 3 131-141)

Stimulus (Observed Other)

Mental Representations Motor Response 1 4 5

Monitoring Synchronization

2a

Rizzolatti & Craighero (2004)


Mental Representations Motor Response 1 4 5


2a

Rizzolatti & Craighero (2004)

Goal Mediated Synchronization

2b


If Goal Activation, then Mental Representations Motor Response Inhibitory/

Excitatory Influences

1 43 5


2a


2b




1 43 5


2a

Simulation

Goal Mediated 2b


If Goal Activation, then

Synchronization

Mental Representations Motor Response Inhibitory/ Excitatory I fl

1 4 3 5


Influences

2a


2b




1 43 5


2a

SimulationCo-Regulation

Semin & Cacioppo, 2008

PsychosocialStress

Central IL-1

ACTH

AdrenalGlands

Glucocorticoids

Epinephrine

Liver

IL-6IL-1ra


SNS

Vagus



MIF

APPs(e.g., CRP)

Epinephrine

Hypothalamus

Pit.

Macrophages

IL-1ra


APPs,IL-1, IL-6

TNF-

IL-6

Glucocorticoids

Macrophages

CRH

Level of Social Integration and Age‐Adjusted Mortality in Five Prospective Studiesy p

House, Landis, & Umberson (1988, Science)

PsychosocialStress

Central IL-1

ACTH

AdrenalGlands

Glucocorticoids

Epinephrine

Liver

IL-6IL-1ra


SNS

Vagus



MIF

APPs(e.g., CRP)

Epinephrine

Hypothalamus

Pit.

Macrophages

IL-1ra


APPs,IL-1, IL-6

TNF-

IL-6

Glucocorticoids

Macrophages

CRH

Experimental Effects of Social Isolation in Non‐Humans• Decreases lifespan of the fruit fly, Drosophilia melanogaster (Ruan & Wu, PNAS,

2008)2008)

• Promotes the development of obesity and Type 2 diabetes in mice (Nonogaki, Nozue, & Oka, Endocrinology, 2007)

• Delays the positive effects of running on adult neurogenesis in rats (StranahanDelays the positive effects of running on adult neurogenesis in rats (Stranahan, Khalil, & Gould, Nature Neuroscience, 2006)

• Increases the activation of the sympatho‐adrenomedullary response to an acute immobilization or cold stressor in rats (Dronjak, Gavrilović, Filipović, & Radojčić, Physiology & Behavior, 2004)

• Decreases the expression of genes regulating glucocorticoid response [glucocorticoid receptor (GR), mineralocorticoid receptor (MR), 11b‐h d t id d h d 1 & 2 (11b HSD1 & 11b HSD2)] i th f t lhydroxysteroid dehydrogenases 1 & 2 (11b‐HSD1 & 11b‐HSD2)] in the frontal cortex of piglets (Poletto, Steibel, Siegford, & Zanella, Brain Research, 2006)

• Decreases open field activity, increased basal cortisol concentrations, and decreased lymphocyte proliferation to mitogens in pigs (Kanitz, Tuchscherer,decreased lymphocyte proliferation to mitogens in pigs (Kanitz, Tuchscherer, Puppe, Tuchscherer, & Stabenow, Brain, Behavior, and Immunity, 2004)

• Larger morning rises in cortisol in squirrel monkeys (Lyons, Ha, & Levine, Hormones and Behavior, 1995)

PsychosocialStress

Central IL-1

ACTH

AdrenalGlands

Glucocorticoids

Epinephrine

Liver

IL-6IL-1ra


SNS

Vagus



MIF

APPs(e.g., CRP)

Epinephrine

Hypothalamus

Pit.

Macrophages

IL-1ra


APPs,IL-1, IL-6

TNF-

IL-6

Glucocorticoids

Macrophages

CRH

• Higher 24 hr urinary catecholamines and evidence of oxidative stress in the aortic arch of the Watanabe Heritable Hyperlipidemic rabbit (Nation, et al., Psychosomatic Medicine, 2008)

Objective vs Perceived Social Isolation

Perceived isolation, or loneliness, is a “gnawing … chronic disease without redeeming features.” (Robert S. Weiss, 1973)( , )

PsychosocialStress

Central IL-1

ACTH

AdrenalGlands

Glucocorticoids

Epinephrine

Liver

IL-6IL-1ra


SNS

Vagus



MIF

APPs(e.g., CRP)

Epinephrine

Hypothalamus

Pit.

Macrophages

IL-1ra


APPs,IL-1, IL-6

TNF-

IL-6

Glucocorticoids

Macrophages

CRH

50

60

70

Ohio State Study (High and Low in Perceived Social Isolation)Isolated

30

40

50

0

10

20

Loneliness Social Shyness Social Skills Anger Anxiety Self Esteem Fear of Neg Optimism Pos Mood Neg Mood

Integrated

70

Loneliness Social Support

Shyness Social Skills Anger Anxiety Self Esteem Fear of Neg Eval

Optimism Pos Mood Neg Mood

f d d ( d l h d l )

40

50

60Stanford University Study (Participants Hypnotized to Feel High and Low Isolation)

Isolated

20

30

40

IntegratedLongitudinal StudiesPsychosocial

Stress

Central IL-1

ACTH

AdrenalGlands

Glucocorticoids

Epinephrine

Liver

IL-6IL-1ra


SNS

Vagus



MIF

APPs(e.g., CRP)

Epinephrine

Hypothalamus

Pit.

Macrophages

IL-1ra


APPs,IL-1, IL-6

TNF-

IL-6

Glucocorticoids

Macrophages

CRH

0

10




60

70Ohio State Study (High and Low in Perceived Social Isolation)

Isolated

30

40

50

0

10

20 Integrated

70




Stanford University Study (Participants Hypnotized to Feel High and Low Isolation)

I l t d

40

50

60Isolated

20

30

40

IntegratedPsychosocial

Stress

Central IL-1

ACTH

AdrenalGlands

Glucocorticoids

Epinephrine

Liver

IL-6IL-1ra


SNS

Vagus



MIF

APPs(e.g., CRP)

Epinephrine

Hypothalamus

Pit.

Macrophages

IL-1ra


APPs,IL-1, IL-6

TNF-

IL-6

Glucocorticoids

Macrophages

CRH

0

10




Big Five Personality StructureBig Five Personality Structure

6 0

7.0

8.0

4.0

5.0

6.0

2.0

3.0 EmbeddedMiddlingLonely

0.0

1.0

gency

blene

ss

usnes

s

Stab

ility

nnes

s

PsychosocialStress

Central IL-1

ACTH

AdrenalGlands

Glucocorticoids

Epinephrine

Liver

IL-6IL-1ra


SNS

Vagus



MIF

APPs(e.g., CRP)

Epinephrine

Hypothalamus

Pit.

Macrophages

IL-1ra


APPs,IL-1, IL-6

TNF-

IL-6

Glucocorticoids

Macrophages

CRH

Surge

Agree

able

Consc

ientio

us

Emotiona

l Sta

Open

The percents of one-person and one-couple only households have been increasing quickly; averagebeen increasing quickly; average household size decreased significantly; proportions of elderly who did not live with children and elderly-couple-only households substantially increased in 2000 as compared to 19901990.

PsychosocialStress

Central IL-1

ACTH

AdrenalGlands

Glucocorticoids

Epinephrine

Liver

IL-6IL-1ra


SNS

Vagus



MIF

APPs(e.g., CRP)

Epinephrine

Hypothalamus

Pit.

Macrophages

IL-1ra


APPs,IL-1, IL-6

TNF-

IL-6

Glucocorticoids

Macrophages

CRH

• Loneliness is higher in the collectivist l f h h hcultures of southern Europe than in the

individualist cultures in northern Europe (Social comparison promotes feelings of(Social comparison promotes feelings of existential isolation when everyone else appears to enjoy a common bond)

PsychosocialStress

Central IL-1

ACTH

AdrenalGlands

Glucocorticoids

Epinephrine

Liver

IL-6IL-1ra


SNS

Vagus



MIF

APPs(e.g., CRP)

Epinephrine

Hypothalamus

Pit.

Macrophages

IL-1ra


APPs,IL-1, IL-6

TNF-

IL-6

Glucocorticoids

Macrophages

CRH

pp j y )

Socioeconomic Capital. . . • Perceived social isolation was unrelated

to:– Household income & education (once marital

status was considered)– Physical attractiveness– Height, weight, body mass index– age, gender, ethnicity– Number of credit hours in college– Scholastic aptitude, motivation, or performance,

and– Number of roommates– Time spent alone

• Perceived social isolation was related to:– Marital status– Number of voluntary associations– Physical health symptoms & disability

PsychosocialStress

Central IL-1

ACTH

AdrenalGlands

Glucocorticoids

Epinephrine

Liver

IL-6IL-1ra


SNS

Vagus



MIF

APPs(e.g., CRP)

Epinephrine

Hypothalamus

Pit.

Macrophages

IL-1ra


APPs,IL-1, IL-6

TNF-

IL-6

Glucocorticoids

Macrophages

CRH

– Chronic work and/or social stress– Small social network– Lack of spousal confidant– Poor quality social relationships (e.g., no

(Cacioppo, Hawkley & Berntson, Current Directions in Psychologial Science, 2003;Hawkley, Hughes, Waite, Masi, Thisted, & Cacioppo, Journal of Gerontology: Social Sciences, in press)

confidants)

Changes in Social Network Size Over Two DecadesOver Two Decades

The modal respondent reported three confidants in 1985; in 2004 the modal number was zero

(McPherson, Smith-Lovin, & Brashears, 2003)

2.5

3

3.5

embe

rs

1985; in 2004 the modal number was zero

1.5

2

.5

1985 (N = 1531)

2004 (N = 1467)

netw

ork

m

0

0.5

1

umbe

r of n

Total network Kin network Non-kin networkNu

◙ General Social Survey◙ 18-89 years old at interview

S i l t k d l

PsychosocialStress

Central IL-1

ACTH

AdrenalGlands

Glucocorticoids

Epinephrine

Liver

IL-6IL-1ra


SNS

Vagus



MIF

APPs(e.g., CRP)

Epinephrine

Hypothalamus

Pit.

Macrophages

IL-1ra


APPs,IL-1, IL-6

TNF-

IL-6

Glucocorticoids

Macrophages

CRH

◙ Social network module◘ Wave 1: 1985, Wave 2: 2004

◙ In 1985, General Social Survey respondents had, on average, 3 people with whom they interacted often. By 2004, social networks had decreased in size by 50%

Intimate Isolation (emotional loneliness)

• 1 * Marital status

R l ti l I l ti

• ‐1 * Marital status

Relational Isolation (social loneliness)

• ‐1 * Frequency of contact with friends & family

C ll ti I l tiCollective Isolation• ‐1 * Number of voluntary

associations

PsychosocialStress

Central IL-1

ACTH

AdrenalGlands

Glucocorticoids

Epinephrine

Liver

IL-6IL-1ra


SNS

Vagus



MIF

APPs(e.g., CRP)

Epinephrine

Hypothalamus

Pit.

Macrophages

IL-1ra


APPs,IL-1, IL-6

TNF-

IL-6

Glucocorticoids

Macrophages

CRH

• 63% reported spending <30 min/day (range = 1 – 107 min/day)min/day)– 11% did not report any

vigorous activity during the past 2 weeks

• Perceived social isolation was associated with a 37% lower likelihood of having engaged in any vigorous exercise over the two previous weeks.

• This effect is evident cross-sectionally and longitudinally and was not mediated by social control but by diff i lf l ti

PsychosocialStress

Central IL-1

ACTH

AdrenalGlands

Glucocorticoids

Epinephrine

Liver

IL-6IL-1ra


SNS

Vagus



MIF

APPs(e.g., CRP)

Epinephrine

Hypothalamus

Pit.

Macrophages

IL-1ra


APPs,IL-1, IL-6

TNF-

IL-6

Glucocorticoids

Macrophages

CRH

differences in self-regulation.

40%ts

30%

40%

ake

from

Fat

20%

10%nt C

alor

ic In

ta

0%Per

cen

PsychosocialStress

Central IL-1

ACTH

AdrenalGlands

Glucocorticoids

Epinephrine

Liver

IL-6IL-1ra


SNS

Vagus



MIF

APPs(e.g., CRP)

Epinephrine

Hypothalamus

Pit.

Macrophages

IL-1ra


APPs,IL-1, IL-6

TNF-

IL-6

Glucocorticoids

Macrophages

CRH

USDA recommend that total fat intake be between 20 and 35% of calories

Executive Functioning: Di h ti Li t i T kDichotic Listening Task

PsychosocialStress

Central IL-1

ACTH

AdrenalGlands

Glucocorticoids

Epinephrine

Liver

IL-6IL-1ra


SNS

Vagus



MIF

APPs(e.g., CRP)

Epinephrine

Hypothalamus

Pit.

Macrophages

IL-1ra


APPs,IL-1, IL-6

TNF-

IL-6

Glucocorticoids

Macrophages

CRH

AgeFemale

Psych1Antidepress1

Psych2Antidepress2

Psych3Antidepress3

Psych4Antidepress4

Psych5Antidepress5

Black HispanicEducationMarried/live‐in partner

L1 L2 L3 L4 L5

Antidepress1PhysFx1

Antidepress2PhysFx2

Antidepress3PhysFx3

Antidepress4PhysFx4

Antidepress5PhysFx5

.707** .707** .707** .707**

115** 115** 115** 115**.115** .115** .115** .115**

.585** .497** .366* .319* .209*

D1 D2 D3 D4 D5

Psych1 Psych2 Psych3 Psych4 Psych5

.549** .549** .549** .549**

.168** . 168** . 168** . 168**

Psych1Antidepress1PhysFx1





AgeFemaleBlack

PsychosocialStress

Central IL-1

ACTH

AdrenalGlands

Glucocorticoids

Epinephrine

Liver

IL-6IL-1ra


SNS

Vagus



MIF

APPs(e.g., CRP)

Epinephrine

Hypothalamus

Pit.

Macrophages

IL-1ra


APPs,IL-1, IL-6

TNF-

IL-6

Glucocorticoids

Macrophages

CRH

HispanicEducationMarried/live‐in partner

She sat by the window, looking inward rather than out. Her thoughts were consumed with her own sadness. She viewed her life as a broken one, and yet she could not place her finger on the exact moment if fell apart. ‘How did I get to f l thi ?’ h t dl k d h lf Bfeel this way?’ she repeatedly asked herself. By asking, she hoped to transcend her depressed state; through understanding, she hoped to repair it Instead her questions led her deeperrepair it. Instead, her questions led her deeper and deeper inside herself – further away from the path that would lead to her recovery (Treynor, Gonzalez & Nolen-Hoeksema “Reumination

PsychosocialStress

Central IL-1

ACTH

AdrenalGlands

Glucocorticoids

Epinephrine

Liver

IL-6IL-1ra


SNS

Vagus



MIF

APPs(e.g., CRP)

Epinephrine

Hypothalamus

Pit.

Macrophages

IL-1ra


APPs,IL-1, IL-6

TNF-

IL-6

Glucocorticoids

Macrophages

CRH

Gonzalez, & Nolen Hoeksema, Reumination reconsidered: A psychometric analysis,” 2003, p. 247).

F li N t O l S d B t I li itl U fFeeling Not Only Sad, But Implicitly Unsafe:Vulnerability During Sleep

90.0Isolated individuals

*

84.0

86.0

88.0

Isolated

showed:• Poorer Sleep Efficiency

78.0

80.0

82.0

y

IntegratedEfficiency• More Wake Time After Sleep Onset

PsychosocialStress

Central IL-1

ACTH

AdrenalGlands

Glucocorticoids

Epinephrine

Liver

IL-6IL-1ra


SNS

Vagus



MIF

APPs(e.g., CRP)

Epinephrine

Hypothalamus

Pit.

Macrophages

IL-1ra


APPs,IL-1, IL-6

TNF-

IL-6

Glucocorticoids

Macrophages

CRH

Sleep Efficiency

(Cacioppo, Hawkley, Berntson, Ernst, Gibbs, Stickgold, & Hobson , Psychological Science, 2002a)

F li N t O l S d B t I li itl U fFeeling Not Only Sad, But Implicitly Unsafe:Vulnerability During Sleep

PsychosocialStress

Central IL-1

ACTH

AdrenalGlands

Glucocorticoids

Epinephrine

Liver

IL-6IL-1ra


SNS

Vagus



MIF

APPs(e.g., CRP)

Epinephrine

Hypothalamus

Pit.

Macrophages

IL-1ra


APPs,IL-1, IL-6

TNF-

IL-6

Glucocorticoids

Macrophages

CRH

Autoregressive cross‐lagged panel model including depressive symptoms, perceived stress, hostility, and social support as additional covariates. Parameter estimates are unstandardized path coefficients. Grey estimates are n.s. at a = .05. (Hawkley, Preacher, Waite, & Cacioppo, 2008)

PsychosocialStress

Central IL-1

ACTH

AdrenalGlands

Glucocorticoids

Epinephrine

Liver

IL-6IL-1ra


SNS

Vagus



MIF

APPs(e.g., CRP)

Epinephrine

Hypothalamus

Pit.

Macrophages

IL-1ra


APPs,IL-1, IL-6

TNF-

IL-6

Glucocorticoids

Macrophages

CRH

=- =

PsychosocialStress

Central IL-1

ACTH

AdrenalGlands

Glucocorticoids

Epinephrine

Liver

IL-6IL-1ra


SNS

Vagus



MIF

APPs(e.g., CRP)

Epinephrine

Hypothalamus

Pit.

Macrophages

IL-1ra


APPs,IL-1, IL-6

TNF-

IL-6

Glucocorticoids

Macrophages

CRH

=- =

- =Psychosocial

Stress

Central IL-1

ACTH

AdrenalGlands

Glucocorticoids

Epinephrine

Liver

IL-6IL-1ra


SNS

Vagus



MIF

APPs(e.g., CRP)

Epinephrine

Hypothalamus

Pit.

Macrophages

IL-1ra


APPs,IL-1, IL-6

TNF-

IL-6

Glucocorticoids

Macrophages

CRH

1150TPR CO

8

1050

1100CO

10007 Isolated

Integrated

900

950

Baseline Prep Speech 6B li P S hBaseline Prep Speech Baseline Prep Speech

PsychosocialStress

Central IL-1

ACTH

AdrenalGlands

Glucocorticoids

Epinephrine

Liver

IL-6IL-1ra


SNS

Vagus



MIF

APPs(e.g., CRP)

Epinephrine

Hypothalamus

Pit.

Macrophages

IL-1ra


APPs,IL-1, IL-6

TNF-

IL-6

Glucocorticoids

Macrophages

CRH

AgeFemaleBlack HispanicpDiplomaSmoker1Exsmoker1BMI1Exercise1Alcohol1Antilipid1CVagent1

Smoker2Exsmoker2BMI2Exercise2Alcohol2Antilipid2CVagent2




L1L1 L2L2 L3L3 L4L4 L5L5.740** .771** .771** .771**

.005 015 015 015

Charlson1g

Charlson2g

Charlson3g

Charlson4g

Charlson5

.015 .015 .015.058 ‐.104 ‐.104 ‐.104

.189† ‐.053 ‐.029 ‐.198† ‐.037

BP1BP1 BP2BP2 BP3BP3 BP4BP4 BP5BP5.513** .489** .489** .489**

.170† .170† .170†

AgeFemaleBlack HispanicDiplomaSmoker1Exsmoker1





PsychosocialStress

Central IL-1

ACTH

AdrenalGlands

Glucocorticoids

Epinephrine

Liver

IL-6IL-1ra


SNS

Vagus



MIF

APPs(e.g., CRP)

Epinephrine

Hypothalamus

Pit.

Macrophages

IL-1ra


APPs,IL-1, IL-6

TNF-

IL-6

Glucocorticoids

Macrophages

CRH

BMI1Exercise1Alcohol1Antilipid1CVagent1Charlson1

Charlson2 Charlson3 Charlson4 Charlson5

† p< .05 * p< .01** p< .001

Cortisol response to awakening (CRTA)

◙ LongitudinalAssociations:Associations:◘ Isolation/Feel

Threatened

◘ Feel fatigued

PsychosocialStress

Central IL-1

ACTH

AdrenalGlands

Glucocorticoids

Epinephrine

Liver

IL-6IL-1ra


SNS

Vagus



MIF

APPs(e.g., CRP)

Epinephrine

Hypothalamus

Pit.

Macrophages

IL-1ra


APPs,IL-1, IL-6

TNF-

IL-6

Glucocorticoids

Macrophages

CRH

(Adam, Hawkley, Kudielka, & Cacioppo, PNAS, 2006)

Day‐SpecificDay BeforeReports

y pMorning Cortisol

ParametersSame DayReports

Day Before Perceived Isolation

CortisolAwakening

Same Day Perceived Isolation

.09** ‐.05

n sPerceived IsolationResponse

Perceived Isolationn.s.

Higher day before loneliness, higher next day awakening

Same Day‐.03 ‐.07*

response

Morning Cortisol

Day Before Fatigue

Higher morning cortisol, less fatigue later that day

n.s.CortisolLevelFatigue

PsychosocialStress

Central IL-1

ACTH

AdrenalGlands

Glucocorticoids

Epinephrine

Liver

IL-6IL-1ra


SNS

Vagus



MIF

APPs(e.g., CRP)

Epinephrine

Hypothalamus

Pit.

Macrophages

IL-1ra


APPs,IL-1, IL-6

TNF-

IL-6

Glucocorticoids

Macrophages

CRH

(Adam, Hawkley, Kudielka, & Cacioppo, PNAS, 2006)

• RNA samples assayed using an Affymetrix U133A high‐density oligonucleotide array to quantify the concentration of gene transcripts in high and low lonely individuals

• The Robust Multi Array Averaging (RMA) algorithm was used• The Robust Multi‐Array Averaging (RMA) algorithm was used to quantify each transcript within each sample

• Seventy‐nine transcripts were over‐expressed and 131 transcripts were under‐expressed in lonely individuals

Isolated

a sc p s e e u de e p essed o e y d dua s

Integrated

Isolation-related transcripts25 50 75 100 1250 150

Difference: p = .0001Up-regulated

25 50 75 100 1250

Down-regulated

150

PsychosocialStress

Central IL-1

ACTH

AdrenalGlands

Glucocorticoids

Epinephrine

Liver

IL-6IL-1ra


SNS

Vagus



MIF

APPs(e.g., CRP)

Epinephrine

Hypothalamus

Pit.

Macrophages

IL-1ra


APPs,IL-1, IL-6

TNF-

IL-6

Glucocorticoids

Macrophages

CRH

Glucocorticoid

033

NF-B

p 011

Difference

p = .033

ene

.40

p = .011

ene

40

.50

10

.12

p = .007

Observed ratio = 5.08(chance: 35/10,000)

mot

er s

ites

/ ge

10

.20

.30

omot

er s

ites

/ ge

.20

.30

.40

.4

.6

.8

.10

olat

ed

pro .10

.00

grat

ed

olat

ed

pro

.10

.00

grat

ed .1 .3 1 100

.2

3Genome cis-structural NF-B / GRE ratio

Iso

Inte

g Iso

Inte

g Genome cis-structural NF-B / GRE ratio

◙ Similarities in the transcription factor binding motif – TFBM – using the TELiS bioinformatics tool suggested less glucocorticoid signaling and more inflammatory signalling in leukocytes of lonely than nonlonely individuals

PsychosocialStress

Central IL-1

ACTH

AdrenalGlands

Glucocorticoids

Epinephrine

Liver

IL-6IL-1ra


SNS

Vagus



MIF

APPs(e.g., CRP)

Epinephrine

Hypothalamus

Pit.

Macrophages

IL-1ra


APPs,IL-1, IL-6

TNF-

IL-6

Glucocorticoids

Macrophages

CRH

0 6

0.7

N = 8,387

0.5

0.6

te (h

2)

0.3

0.4

ritab

ility

Est

imat

0.1

0.2He

0Heritability EnvironmentHeritability Environmental

PsychosocialStress

Central IL-1

ACTH

AdrenalGlands

Glucocorticoids

Epinephrine

Liver

IL-6IL-1ra


SNS

Vagus



MIF

APPs(e.g., CRP)

Epinephrine

Hypothalamus

Pit.

Macrophages

IL-1ra


APPs,IL-1, IL-6

TNF-

IL-6

Glucocorticoids

Macrophages

CRH

(Boomsma, Willemse, Dolan, Hawkley, & Cacioppo , Behavior Genetics, 2005)

Boomsma, D. I., Cacioppo, J. T., Slagboom, P. E., & Posthuma, D. (2006). Genetic linkage and association analysis for loneliness in Dutch twin and sibling pairs points to a region on chromosome 12q23-24. Behavior Genetics.

Replications & Other Associations of Social Isolation in HumansSocial Isolation in Humans

• Increased hypothalamic pituitary adrenocortical activity (Steptoe et al., 2004)

L l b i l (J b t l J l f th A i G i t i• Less salubrious sleep (Jacobs et al., Journal of the American Geriatric Society, 2006; Pressman et al., Health Psychology, 2005)

• Progression of Alzheimer’s Disease (Wilson et al., Archives of General P hi t 2007)Psychiatry, 2007)

• Obesity (Lauder et al., Psychology, Health, & Medicine, 2006)

• Diminished immunity (Kiecolt‐Glaser et al., Psychosomatic Medicine, 1984; Pressman et al., Health Psychology, 2005)

• Reduction in independent living (Russell et al., Psychology & Aging, 1997)

• Alcoholism (Akerlind & Hornquist, Social Science & Medicine, 1992)

• Depression (Heikkinen & Kauppinen, Archives of Gerontology and Geriatrics, 2004; ) and suicidal ideation and behavior (Rudatsikira,

PsychosocialStress

Central IL-1

ACTH

AdrenalGlands

Glucocorticoids

Epinephrine

Liver

IL-6IL-1ra


SNS

Vagus



MIF

APPs(e.g., CRP)

Epinephrine

Hypothalamus

Pit.

Macrophages

IL-1ra


APPs,IL-1, IL-6

TNF-

IL-6

Glucocorticoids

Macrophages

CRH

Muula, Siziya, & Twa‐twa, BMC Psychiatry, 2007)

• Poorer health (Caspi et al., Archives of Pediatric Adolescent Medicine, 2006; Seeman , American Journal of Health Promotion, 2000)

Exposure to

Perceived Stress and Coping

Stp

Stressors & Life Events Stress Response

RecuperativeProcesses

HealthBehaviors

osocialess

Central IL-1

ACTH

nalds

Glucocorticoids

Epinephrine

Liver

IL-6IL-1ra


SNS

Vagus



MIF

APPs(e.g., CRP)

ne

Hypothalamus

Pit.

Macrophages

IL-1ra


APPs,IL-1, IL-6

TNF-

IL-6

Glucocorticoids

Macrophages

CRH

AGE

Physiological Resilience(1-Allostatic Load)

Social Isolation

Multilevel Selection Theory: Perceived Social Isolation as an Aversive Signal to Motivate Reconnection and Shared Efforts

• Genes that promote behavior which increases the odds of the genes survivingincreases the odds of the genes surviving are perpetuated– This usually means the organism is

also more likely to survive to procreateprocreate

◙ Selfish genes, social animals: The genes of hunter/gatherers who did not feel a compulsion to bond and to return to share compulsion to bond and to return to sharetheir food and defense with their offspring may have survived to procreate but their offspring were less likely to survive to procreate.

◙ The aversiveness of isolation, in this conceptualization, is the social equivalent of physical pain with a design to maintain or promote the social connection necessary for

pPsychosocial

Stress

Central IL-1

ACTH

AdrenalGlands

Glucocorticoids

Epinephrine

Liver

IL-6IL-1ra


SNS

Vagus



MIF

APPs(e.g., CRP)

Epinephrine

Hypothalamus

Pit.

Macrophages

IL-1ra


APPs,IL-1, IL-6

TNF-

IL-6

Glucocorticoids

Macrophages

CRH

promote the social connection necessary for the survival of the genes.

With GratitudeLouise Hawkley, Ph.D., University of ChicagoGary Berntson, Ph.D., Ohio State UniversityLinda Waite, Ph.D., University of ChicagoChris Masi, M.D.,Ph.D., University of Chicago

Jia‐Hong Gao, Ph.D., University of Chicago

William Malarkey, M.D., Ohio State UniversityChris Masi, M.D.,Ph.D., University of Chicago

Ron Thisted, Ph.D., University of ChicagoM.E. Hughes, Ph.D., Johns Hopkins UniversityDorett I. Boomsma, Ph.D., Free UniversityB i i K di lk Ph D T i U i i

yThomas McDade, Ph.D., Northwestern University

John M. Ernst, Ph.D., Illinois WesleyanGonneke Willemsen Ph D Free UniversityBrigitte Kudielka, Ph.D., Trier University

Ming Wen, Ph.D., University of UtahMichael Browne, Ph.D., Ohio State UniversityDavid Spiegel, M.D., Stanford University

Gonneke Willemsen, Ph.D., Free UniversityM. Bartels, Free UniversityC. E. M. van Beijsterveldt, Ph.D., Free UniversityMary Burleson, Ph.D., Arizona State Universityp g , , y

J. Allan Hobson, M.D., Harvard UniversityRobert Stickgold, Ph.D., Harvard UniversityRobert Rose, M.D., MacArthur FoundationSteve Cole Ph D UCLA

Emma Adam, Ph.D., Northwestern UniversityCatherine Norris, Ph.D., University of WisconsinSteven Small, M.D., Ph.D., University of ChicagoJean Decety Ph D University of ChicagoSteve Cole, Ph.D., UCLA

Phil Marucha, Ph.D., Ohio State UniversityJarett Berry, M.D., Northwestern UniversityBen Converse, University of Chicago

Jean Decety, Ph.D., University of ChicagoAdam Waytz, M.A., University of ChicagoNick Epley, Ph.D., University of ChicagoYuejia Luo, Beijing Normal University

Shihui Han, Ph.D., Peking University Tatia Lee, University of Hong Kong

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