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Socioeconomic Status and Children’s Health:
Investigating Levels of Influence
Edith Chen, Ph.D.University of British Columbia
Gradient Effect for Adult Health
(Adler et al., Am Psychol, 1994)
0
3
6
9
12
15
1 2 3 4 5
SES (lowest to highest)
Pre
va
len
ce
of
he
alt
h p
rob
lem
Low birthweightInjury
SedentarybehaviorAsthma
25
22
19
10
13
16
9
8
7
6
5
4
6
5
4
3
2
1
SB I LBW A
Similar Gradient in Childhood
(Chen et al., Psych Bull, 2002)
1) What are the biological pathways through which low SES comes to affect childhood health?
2) What psychosocial processes connect SES to these biological markers?
Research Questions
(Pamuk et al, 1998)
Low SES Associated with Asthma Hospitalizations
0
1
2
3
4
5
<20K 20-30K 30-40K 40+K
Median household income (1989 dollars)
Ast
hm
a h
osp
ital
izat
ion
rat
e (/
1000
p
op
ula
tio
n)
TAPC
T
IL-5IL-4
IL-13
APC
T
B
Eosinophils
IL-5IL-4
IL-13
APC
IgE
T
B
Eosinophils
IL-5IL-4
IL-13
APC
IgE
PBMC
PMA/INO
In Vitro Testing
PBMC
PMA/INO
In Vitro Testing
PBMC
IL-5
IL-4
IL-13
PMA/INO
In Vitro Testing
(Chen et al., J Allergy & Clin Immunol, 2006)
Cytokine Production Differs by SES in Asthma Group
(Chen et al., J Allergy & Clin Immunol, 2006)
SES – Immune Relationship is Linear
= -.39, p<.05
Bacteria
TLR-4
BacteriaTLR-4
NF-B
TLR-4
NF-B
TLR-4
NF-B
TLR-4
NF-B
TLR-4
Cortisol
EpiNorepi
GR
2AR
CREBGR
2AR
NF-B
CREBGR
NF-B CREBGR
Microarrays & Bioinformatics
Subgroup of low and high SES youth with asthmaGenome-wide transcriptional profiling done with
microarrays on T cellsRobust multiarray averaging quantifies expression
of ~14,500 genesIdentifies differentially expressed genes (≥ 1.3-fold
expression disparity between groups)Using TELiS, a bioinformatics software program,
estimate the underlying transcription factor activity that drives differential gene expression
SES Associated with Differential Transcription Factor Activity
(Chen et al., Thorax, 2009)
NF-BNFY
CREB
2AR
TLR-4
NF-B could suggest alteration of signaling pathway shifting to >inflammatory phenotype
CREB/NFY could suggest diminished efficacy of beta agonist medications for asthma
Children lower in socioeconomic status show heightened inflammatory profiles in a direction consistent with their experience of greater clinical morbidity in asthma
Effects of SES seen at multiple biological levels: inflammatory proteins gene expression transcription factor activity
Interim Summary
1) What are the biological pathways through which low SES comes to affect childhood health?
2) What psychosocial processes connect SES to these biological markers?
Research Questions
Low SES children grow up in environments where negative events happen frequently
Individual: Perceptions of Threat
Develop a tendency toward interpreting the world as a threatening place that requires heightened vigilance
Low SES associated with greater appraisals of threat during ambiguous social situations
Measuring Threat Interpretations:CAUSE Video Coding
-2 -1 0 +1 +2 Very Mixed Very Benign Threatening
Very benign: “Maybe it was about the homeworkassignment. Or maybe he thought I could helphim figure out who the cheaters were.”
Very threatening: “He’s going to accuse me ofcheating. He probably didn’t believe that I could do aswell on the test as I did, so I must have cheated.”
A: t (28) = 2.99, p < .01N: t (28) = 0.25, ns
(Chen et al., Psychosomatic Medicine, 2003)
-2
-1
0
1
2
Ambiguous Negative
Thre
at I
nter
pret
atio
n(low
to
high
)Low SES
High SES
Interpretations Differ by SES for Ambiguous Situations Only
Statistical Mediation: Sobel Test, Z>.97, p<.05 using distributional properties recommended by MacKinnon. +p<.10, **p<.01
(Chen et al., J Allergy & Clin Immunol, 2006)
Z=1.17, p<.05
Threat Appraisal Forms One PathwayBetween SES and Cytokine Production
=-.40** =.28+
SESThreat Apprais
al
IL-5 IL-13
Controlling Appraisal t p t p
SES – CREB 2.22 .031 1.16 .25
SES – NF-B 2.18 .032 1.58 .12
Controlling for Threat Appraisal Reduces SES Differences in Transcription Factor Signaling Pathways
(Chen et al., Thorax, 2009)
Children from lower SES backgrounds perceive their social world in more threatening ways, and this in turn has implications for asthma inflammatory responses
At the Individual Level:
Role of Family Stress
Some evidence based on clinical research that combinations of stressors – e.g., acute + chronic stress can predict onset of new asthma attacks (Sandberg, 2000)
How does family stress contribute to asthma biological profiles?
Role of Family Stress
Outcomes: Asthma-relevant cytokine production Gene expression (mRNA) for glucocorticoid receptor (GR) beta 2 adrenergic receptor (2AR)
UCLA Life Stress Interview -open ended, semi-structured -probes ongoing difficulties + acute events -team ratings that take into account context
Acute + Chronic Family Stress Increases Cytokine Production
(Marin et al., Psychosomatic Medicine, 2009)
11= 8.16, SE=3.15, p=.01 11=43.74, SE=15.46, p=.007
0
2.5
5
7.5
Yes NoMajor Life Event + Chronic Family Stress
GR
mR
NA
(R
Q lo
g-2
)
Asthma
Healthy
(Miller & Chen, Proc Natl Acad Sci, 2006)
Acute + Chronic Stress Reduces GR Gene Expression in Asthma
Acute + Chronic Stress Reduces 2AR Gene Expression in
Asthma
(Miller & Chen, Proc Natl Acad Sci, 2006)
Experiencing an acute negative life event on top of high chronic family stress is most detrimental to asthma inflammatory profiles
At the Family Level:
Neighborhood Effects
(Chen & Miller, Brain Beh Immun, 2007)
Neighborhood Effects
Neighborhood: Air Pollution
Physical EnvironmentTraffic-related air pollution (NO2)
116 passive samplers GIS + land use regression model
Social EnvironmentChronic family stress
Immune markers Th-2 cytokines, IgE, eosinophils Longitudinal clinical outcomes Symptoms, peak flow
0
30
60
90
120
150
Low High
Chronic family stress
IL-5
(p
g/m
l)Low pollution
High pollution
Effects of Stress Emerge in Modest Pollution Areas
(Chen et al, Env Health Persp, 2008)Interaction β = –0.31, p = 0.02
-2
0
2
4
6
Low High
Chronic family stress
Ch
ang
e in
ch
ild
-rep
ort
ed d
aily
dia
ry
sym
pto
ms
ove
r 6
mo
nth
sLow pollution
High pollution
Stress Linked to Increases in Symptoms in Modest Pollution
Areas
(Chen et al, Env Health Persp, 2008)Interaction β = –0.28, p = 0.02
Adverse family environments potentiate the effects of modest neighborhood physical environmental exposures on asthma biological and clinical outcomes
Combined Effects across Levels:
SES
Asthma morbidi
ty
SES
Asthma morbidi
ty
Cellular functio
n
SES
Asthma morbidi
ty
Cellular functio
n
Genomic
activity
SES
Asthma morbidi
ty
Cellular functio
n
Genomic
activity
Threat apprais
al
SES
Asthma morbidi
ty
Cellular functio
n
Genomic
activity
Threat apprais
al
Family stress
Physical exposures
Social exposures
Our previous work has focused on mediational pathways, which is inherently a main effects model
Why Do Some Children Do Well?
Some individuals thrive despite facing adverse circumstances – notion of resilience
How do some individuals, despite experiencing the greater stress associated with poverty, maintain positive physiological health profiles?
Secondary coping for dealing with immediate stressors -reappraisals, emotion regulation associated with better clinical outcomes (Bower, 1998; Salovey 2002; Affleck, 1987) -goodness-of-fit of strategy with circumstance beneficial for health, physiological responses (Heckhausen 2001; Bennett 2004; Siegrist 1997)
Adaptive Persistence
Behavioral persistence in striving for long-term goals -pursuing goals associated with lower daily cortisol secretion (Hoppmann, 2006) -purpose in life associated with lower cortisol, lower sIL-6r (Ryff 2004)
Why would some individuals in low SES environments display adaptive persistence?
Roots of Adaptive Persistence
Underlying belief about world and others as trustworthy, dependable, future as bright -hostility, social support, optimism all linked to physiological & clinical health outcomes (Smith, 1992; Cohen, 1997; Scheier, 1999) Beliefs shaped by broader social context -experiences with positive role model facilitate development of these beliefs, via attachment and socialization of norms (Mikulincer, 2003; Eisenberg, 1997)
Could positive role models early in life protect even those who are low in SES from detrimental inflammatory profiles later in life?
Early Life Social Contexts
Adversity early in life predicts heightened inflammation (CRP) in adulthood (Taylor 2006; Danese 2007)
What mechanisms explain how early environments come to have effects on later health?
Healthy adults ages 25-40
Method
Either low in early life SES or high in early life SES, by parent report of occupation
Genome-wide transcriptional profiling done with microarrays on PBMCs
Low Early Life SES Associated with Increased Pro-Inflammatory Signaling
(Miller et al., Proc Natl Acad Sci, 2009)
Could positive role models early in life persistently alter this inflammatory trajectory into adulthood? -Developmental psychopathology literature shows examples of psychological resilience through supportive family relationships (Werner 1995; Masten 1998; Luthar 1996) -Animal literature shows maternal licking & grooming early in life to reduce physiological stress responses in adulthood (Liu 1997)
Resilience
Subsample that was low in SES early in life
Compared those low vs. high in childhood maternal warmth (Parental Bonding Inventory)
High Maternal Warmth Reduces Pro-Inflammatory Signaling Among Low SES
(Chen et al., Molecular Psychiatry, in press)
High Maternal Warmth Reduces Pro-Inflammatory Cytokine Production
(Chen et al., Molecular Psychiatry, in press)
Maternal warmth can offset the detrimental effects of early life adversity on adult pro-inflammatory signaling pathways.
This may be because positive role models foster the development of benevolent views about others and the world that acutely lead to adaptive psychological and physiological responses to stress, and over time reduce the long-term toll on pathogenic mechanisms related to chronic inflammation
Broader social context
Thanks to:
Gregory Miller Alexandra GaudinSteve Cole Margaret HansonRobert Strunk Hannah SchreierMichael Brauer Hope WalkerGaye McDonald-Jones Meanne Chan