the anatomy of loneliness · 2008. 10. 30. · (e.g., crp) epinephrine hypothalamus pit....
TRANSCRIPT
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
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
• 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
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
Structure and Capabilities of a pConnected Collective
PsychosocialStress
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
PsychosocialStress
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
PsychosocialStress
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
PsychosocialStress
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
PsychosocialStress
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
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
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
• 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
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)
Stimulus (Observed Other)
Mental Representations Motor Response 1 4 5
Monitoring Synchronization
2a
Rizzolatti & Craighero (2004)
Goal Mediated Synchronization
2b
Stimulus (Observed Other)
If Goal Activation, then Mental Representations Motor Response Inhibitory/
Excitatory Influences
1 43 5
Monitoring Synchronization
2a
Goal Mediated Synchronization
2b
Stimulus (Observed Other)
If Goal Activation, then Mental Representations Motor Response Inhibitory/
Excitatory Influences
1 43 5
Monitoring Synchronization
2a
Simulation
Goal Mediated 2b
Stimulus (Observed Other)
If Goal Activation, then
Synchronization
Mental Representations Motor Response Inhibitory/ Excitatory I fl
1 4 3 5
Monitoring Synchronization
Influences
2a
Goal Mediated Synchronization
2b
Stimulus (Observed Other)
If Goal Activation, then Mental Representations Motor Response Inhibitory/
Excitatory Influences
1 43 5
Monitoring Synchronization
2a
SimulationCo-Regulation
Semin & Cacioppo, 2008
PsychosocialStress
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
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
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
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
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
• 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
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
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
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
0
10
Loneliness Social Support
Shyness Social Skills Anger Anxiety Self Esteem Fear of Neg Eval
Optimism Pos Mood Neg Mood
60
70Ohio State Study (High and Low in Perceived Social Isolation)
Isolated
30
40
50
0
10
20 Integrated
70
Loneliness Social Support
Shyness Social Skills Anger Anxiety Self Esteem Fear of Neg Eval
Optimism Pos Mood Neg Mood
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
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
0
10
Loneliness Social Support
Shyness Social Skills Anger Anxiety Self Esteem Fear of Neg Eval
Optimism Pos Mood Neg Mood
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
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
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
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
• 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
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
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
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
– 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
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
◙ 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
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
• 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
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
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
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
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
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
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
Psych2Antidepress2PhysFx2
Psych3Antidepress3PhysFx3
Psych4Antidepress4PhysFx4
Psych5Antidepress5PhysFx5
AgeFemaleBlack
PsychosocialStress
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
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
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
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
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
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
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
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
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
=- =
PsychosocialStress
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
=- =
- =Psychosocial
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
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
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
AgeFemaleBlack HispanicpDiplomaSmoker1Exsmoker1BMI1Exercise1Alcohol1Antilipid1CVagent1
Smoker2Exsmoker2BMI2Exercise2Alcohol2Antilipid2CVagent2
Smoker3Exsmoker3BMI3Exercise3Alcohol3Antilipid3CVagent3
Smoker4Exsmoker4BMI4Exercise4Alcohol4Antilipid4CVagent4
Smoker5Exsmoker5BMI5Exercise5Alcohol5Antilipid5CVagent5
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
Smoker2Exsmoker2BMI2Exercise2Alcohol2Antilipid2CVagent2
Smoker3Exsmoker3BMI3Exercise3Alcohol3Antilipid3CVagent3
Smoker4Exsmoker4BMI4Exercise4Alcohol4Antilipid4CVagent4
Smoker5Exsmoker5BMI5Exercise5Alcohol5Antilipid5CVagent5
PsychosocialStress
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
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
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
(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
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
(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
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
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
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
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
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
(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
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
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
Systemic markers of inflammation
SNS
Vagus
Reticulo-endothelial
System (e.g., Spleen)
MIF
APPs(e.g., CRP)
ne
Hypothalamus
Pit.
Macrophages
IL-1ra
Leukocytes(e.g., Macrophages)
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
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
promote the social connection necessary for the survival of the genes.
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
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
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