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