adverse childhood experiences and the origins of adult disease evidence from the dunedin study
DESCRIPTION
Adverse Childhood Experiences and the Origins of Adult Disease Evidence from the Dunedin Study Andrea Danese, M.D. M.Sc. Department of Child & Adolescent Psychiatry and Social, Genetic, and Developmental Psychiatry (SGDP) Centre Institute of Psychiatry, King’s College London, UK. - PowerPoint PPT PresentationTRANSCRIPT
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Adverse Childhood Experiences and the Origins of Adult Disease
Evidence from the Dunedin Study
Andrea Danese, M.D. M.Sc.Department of Child & Adolescent Psychiatry
and Social, Genetic, and Developmental Psychiatry (SGDP) Centre
Institute of Psychiatry, King’s College London, UK
![Page 2: Adverse Childhood Experiences and the Origins of Adult Disease Evidence from the Dunedin Study](https://reader035.vdocument.in/reader035/viewer/2022070403/568139d4550346895da18832/html5/thumbnails/2.jpg)
introduction
enduring effects of child stress
timing matters
developing allostatic load
conclusions
![Page 3: Adverse Childhood Experiences and the Origins of Adult Disease Evidence from the Dunedin Study](https://reader035.vdocument.in/reader035/viewer/2022070403/568139d4550346895da18832/html5/thumbnails/3.jpg)
> introduction
enduring effects of child stress
timing matters
developing allostatic load
conclusions
![Page 4: Adverse Childhood Experiences and the Origins of Adult Disease Evidence from the Dunedin Study](https://reader035.vdocument.in/reader035/viewer/2022070403/568139d4550346895da18832/html5/thumbnails/4.jpg)
McEwen B et al, Nature 1968, 220:911-2
MIND & BODY
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+
+
_
_AMYGDALA, HIPPOCAMPUS
+GR
GR
Heim C et al, Psychoneuroendocrinology 2008, 33: 693-710
= /
CHILD STRESS AND HPA AXIS
![Page 6: Adverse Childhood Experiences and the Origins of Adult Disease Evidence from the Dunedin Study](https://reader035.vdocument.in/reader035/viewer/2022070403/568139d4550346895da18832/html5/thumbnails/6.jpg)
> Innate immunity
Body physical barriers (e.g., skin, gastrointestinal tract)
Non-self recognition (complement system, Toll-like receptors)
Activation (cytokines, endothelial cells)
Response (phagocytes, acute phase proteins)
INFLAMMATION
![Page 7: Adverse Childhood Experiences and the Origins of Adult Disease Evidence from the Dunedin Study](https://reader035.vdocument.in/reader035/viewer/2022070403/568139d4550346895da18832/html5/thumbnails/7.jpg)
Ridker P et al, N Engl J Med 1997, 336:973-9
INFLAMMATION & DISEASE
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STRESS
SYMPATHETIC
PARASYMPATHETIC
GLUCOCORTICOIDS
+ -
-
INFLAMMATION REGULATION
![Page 9: Adverse Childhood Experiences and the Origins of Adult Disease Evidence from the Dunedin Study](https://reader035.vdocument.in/reader035/viewer/2022070403/568139d4550346895da18832/html5/thumbnails/9.jpg)
INFLAMMATION REGULATIONAND CHILD STRESS
STRESS
SYMPATHETIC
PARASYMPATHETIC
GLUCOCORTICOIDS
+ -
-
![Page 10: Adverse Childhood Experiences and the Origins of Adult Disease Evidence from the Dunedin Study](https://reader035.vdocument.in/reader035/viewer/2022070403/568139d4550346895da18832/html5/thumbnails/10.jpg)
> Increased adult risk for:
OR 95% CI
Chronic lung disease 3.9 [2.6-5.8]
Cardiovascular disease 2.2 [1.3-3.7]
Cancer 1.9 [1.3-2.7]
Diabetes 1.6 [1.0-2.5]
Felitti V et al, Am J Prev Med 1998, 14:245-58
CHILD STRESS AND DISEASE RISK
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ADULT DISEASE RISK
THE EPIGENETIC LANDSCAPE
Genes
TIME
(age)
Waddington CH, 1975
E1 (t1)
E1 (t2)
E2 (t3)
![Page 12: Adverse Childhood Experiences and the Origins of Adult Disease Evidence from the Dunedin Study](https://reader035.vdocument.in/reader035/viewer/2022070403/568139d4550346895da18832/html5/thumbnails/12.jpg)
introduction
> enduring effects of child stress
timing matters
developing allostatic load
conclusions
![Page 13: Adverse Childhood Experiences and the Origins of Adult Disease Evidence from the Dunedin Study](https://reader035.vdocument.in/reader035/viewer/2022070403/568139d4550346895da18832/html5/thumbnails/13.jpg)
THE DUNEDIN STUDY
Representative birth cohort followed up from birth to age 32y
N=972 (at age 32 years)
Childhood maltreatment (multiple informants, multiple time points)
High-sensitivity CRP (>3mg/dL, cont), fibrinogen, white blood cell count
Risk factors and potential mediating variables throughout life-course
Cox, OLS regression analysis
![Page 14: Adverse Childhood Experiences and the Origins of Adult Disease Evidence from the Dunedin Study](https://reader035.vdocument.in/reader035/viewer/2022070403/568139d4550346895da18832/html5/thumbnails/14.jpg)
CHILDHOOD MALTREATMENT
Maternal rejection (14%)
Harsh discipline (10%)
Disruptive caregivers changes (6%)
Physical abuse (4%)
Sexual abuse (12%)
1 ≥20
No Probable Definite
AGE 3-11 YEARS
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MALTREATMENT AND ADULT INFLAMMATIONHIGH RISK GROUP FOR CARDIOVASCULAR DISEASE (CDC, AHA)
01
02
03
04
0
No Probable Definite
Childhood maltreatment
hsC
RP
> 3
mg
/L (
%)
Danese A et al, PNAS 2007, 104:1319-24
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RR = 1.80 [1.26-2.58]
MALTREATMENT AND ADULT INFLAMMATION
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?
*Low birth weight. RR = 1.60 [1.00-2.57]
*Low child SES. RR = 1.96 [1.19-3.25]
*Low child IQ. RR = 1.44 [1.03-2.01]
*Low birth weight. RR = 0.87 [0.49-1.53]
*Low child SES. RR = 1.89 [1.50-2.39]
*Low child IQ. RR = 2.12 [1.56-2.87]
RR = 1.80 [1.26-2.58]
CO-OCCURRING EARLY-LIFE RISKSMALTREATMENT AND ADULT INFLAMMATION
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*Low birth weight. RR = 1.60 [1.00-2.57]
*Low child SES. RR = 1.96 [1.19-3.25]
*Low child IQ. RR = 1.44 [1.03-2.01]
*Low birth weight. RR = 0.87 [0.49-1.53]
*Low child SES. RR = 1.89 [1.50-2.39]
*Low child IQ. RR = 2.12 [1.56-2.87]
RR = 1.80 [1.26-2.58]
CO-OCCURRING EARLY-LIFE RISKSMALTREATMENT AND ADULT INFLAMMATION
RR = 1.58 [1.08-2.31]
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*Low adult SES. RR = 1.44 [0.94-2.20]
*Major Depression. RR = 1.45 [1.06-1.99]
*High Perc. Stress. RR = 1.45 [1.08-1.94]
*Low adult SES. RR = 1.48 [1.23-1.73]
*Major Depression. RR = 1.46 [1.10-1.94]
*High Perc. Stress. RR = 1.43 [1.12-1.82]
?
RR = 1.80 [1.26-2.58]
ADULT STRESS EXPOSUREMALTREATMENT AND ADULT INFLAMMATION
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*Low adult SES. RR = 1.44 [0.94-2.20]
*Major Depression. RR = 1.45 [1.06-1.99]
*High Perc. Stress. RR = 1.45 [1.08-1.94]
*Low adult SES. RR = 1.48 [1.23-1.73]
*Major Depression. RR = 1.46 [1.10-1.94]
*High Perc. Stress. RR = 1.43 [1.12-1.82]
RR = 1.80 [1.26-2.58]
ADULT STRESS EXPOSUREMALTREATMENT AND ADULT INFLAMMATION
RR = 1.64 [1.13-2.40]
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*CV risk cluster. RR = 2.38 [1.84-3.10]
*Smoking. RR = 1.18 [0.69-2.03]
*Physical inactivity. RR = 1.57 [1.05-2.34]
*Diet. RR = 1.01 [0.68-1.48]
*CV risk cluster. RR = 1.48 [1.10-2.00]
*Smoking. RR = 1.91 [1.13-3.23]
*Physical inactivity. RR = 0.87 [0.69-1.11]
*Diet. RR = 0.98 [0.78-1.23]
?
RR = 1.80 [1.26-2.58]
ADULT HEALTH & HEALTH BEHAVIOURSMALTREATMENT AND ADULT INFLAMMATION
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*CV risk cluster. RR = 2.38 [1.84-3.10]
*Smoking. RR = 1.18 [0.69-2.03]
*Physical inactivity. RR = 1.57 [1.05-2.34]
*Diet. RR = 1.01 [0.68-1.48]
*CV risk cluster. RR = 1.48 [1.10-2.00]
*Smoking. RR = 1.91 [1.13-3.23]
*Physical inactivity. RR = 0.87 [0.69-1.11]
*Diet. RR = 0.98 [0.78-1.23]
RR = 1.80 [1.26-2.58]
ADULT HEALTH & HEALTH BEHAVIOURSMALTREATMENT AND ADULT INFLAMMATION
RR = 1.76 [1.23-2.51]
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MALTREATMENT AND ADULT INFLAMMATION
Danese A et al, PNAS 2007, 104:1319-24
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SUMMARY (1)
> Maltreated children show a significant and graded elevation in inflammation levels 20 years later, in adulthood.
> The effect of childhood maltreatment on adult inflammation is independent of the influence of co-occurring risk factors.
> 10% of the cases of inflammation in the population may be attributable to childhood maltreatment.
![Page 25: Adverse Childhood Experiences and the Origins of Adult Disease Evidence from the Dunedin Study](https://reader035.vdocument.in/reader035/viewer/2022070403/568139d4550346895da18832/html5/thumbnails/25.jpg)
introduction
enduring effects of child stress
> timing matters
developing allostatic load
conclusions
![Page 26: Adverse Childhood Experiences and the Origins of Adult Disease Evidence from the Dunedin Study](https://reader035.vdocument.in/reader035/viewer/2022070403/568139d4550346895da18832/html5/thumbnails/26.jpg)
ADULT DISEASE RISK
THE EPIGENETIC LANDSCAPE
Genes
TIME
(age)
Waddington CH, 1975
E1 (t1)
E1 (t2)
E2 (t3)
![Page 27: Adverse Childhood Experiences and the Origins of Adult Disease Evidence from the Dunedin Study](https://reader035.vdocument.in/reader035/viewer/2022070403/568139d4550346895da18832/html5/thumbnails/27.jpg)
Danese A et al, Arch Gen Psychiatry 2008, 65: 409-15
CHILD STRESS vs ADULT STRESS
01
02
03
04
05
0
No stress Adult stress Child stress Adult+Child stress
Ad
ult
hsC
RP
> 3
mg
/L (
%)
(N=673) (N=109) (N=56) (N=27)
![Page 28: Adverse Childhood Experiences and the Origins of Adult Disease Evidence from the Dunedin Study](https://reader035.vdocument.in/reader035/viewer/2022070403/568139d4550346895da18832/html5/thumbnails/28.jpg)
Danese A et al, Arch Gen Psychiatry 2008, 65: 409-15
CHILD STRESS vs ADULT STRESS
01
02
03
04
05
0
No stress Adult stress Child stress Adult+Child stress
Ad
ult
hsC
RP
> 3
mg
/L (
%)
(N=673) (N=109) (N=56) (N=27)
![Page 29: Adverse Childhood Experiences and the Origins of Adult Disease Evidence from the Dunedin Study](https://reader035.vdocument.in/reader035/viewer/2022070403/568139d4550346895da18832/html5/thumbnails/29.jpg)
Danese A et al, Arch Gen Psychiatry 2008, 65: 409-15
CHILD STRESS vs ADULT STRESS
01
02
03
04
05
0
No stress Adult stress Child stress Adult+Child stress
Ad
ult
hsC
RP
> 3
mg
/L (
%)
(N=673) (N=109) (N=56) (N=27)
*
![Page 30: Adverse Childhood Experiences and the Origins of Adult Disease Evidence from the Dunedin Study](https://reader035.vdocument.in/reader035/viewer/2022070403/568139d4550346895da18832/html5/thumbnails/30.jpg)
Danese A et al, Arch Gen Psychiatry 2008, 65: 409-15
CHILD STRESS vs ADULT STRESS
01
02
03
04
05
0
No stress Adult stress Child stress Adult+Child stress
Ad
ult
hsC
RP
> 3
mg
/L (
%)
(N=673) (N=109) (N=56) (N=27)
* *
![Page 31: Adverse Childhood Experiences and the Origins of Adult Disease Evidence from the Dunedin Study](https://reader035.vdocument.in/reader035/viewer/2022070403/568139d4550346895da18832/html5/thumbnails/31.jpg)
CHILD STRESS vs ADULT STRESS
Danese A et al, Arch Gen Psychiatry 2008, 65: 409-15
Adult stress (N=109) Child stress (N=56) Adult+Child stress (N=27)
Effe
ct S
ize
(d
)
0.0
0.1
0.2
0.3
0.4
0.5
Inflammation factor(log) hsCRPFibrinogenWhite Blood Cells
vs No stress (N=673) vs No stress (N=673) vs No stress (N=673)
![Page 32: Adverse Childhood Experiences and the Origins of Adult Disease Evidence from the Dunedin Study](https://reader035.vdocument.in/reader035/viewer/2022070403/568139d4550346895da18832/html5/thumbnails/32.jpg)
SUMMARY (2)> Stress in childhood may modify developmental trajectories and have long-term effect on disease risk.
> If stress does modify developmental trajectories, more favourable conditions later in life may have little effect on disease risk.
> Stress later in life may have a smaller effect on disease risk, because it acts on a more developed system.
![Page 33: Adverse Childhood Experiences and the Origins of Adult Disease Evidence from the Dunedin Study](https://reader035.vdocument.in/reader035/viewer/2022070403/568139d4550346895da18832/html5/thumbnails/33.jpg)
introduction
enduring effects of child stress
timing matters
> developing allostatic load
conclusions
![Page 34: Adverse Childhood Experiences and the Origins of Adult Disease Evidence from the Dunedin Study](https://reader035.vdocument.in/reader035/viewer/2022070403/568139d4550346895da18832/html5/thumbnails/34.jpg)
ADULT DISEASE RISK
THE EPIGENETIC LANDSCAPE
Genes
TIME
(age)
Waddington CH, 1975
E1 (t1)
E1 (t2)
E2 (t3)
![Page 35: Adverse Childhood Experiences and the Origins of Adult Disease Evidence from the Dunedin Study](https://reader035.vdocument.in/reader035/viewer/2022070403/568139d4550346895da18832/html5/thumbnails/35.jpg)
Danese A et al (submitted)
CHILD EXPERIENCES AND ADULT HEALTHMALTREATMENT, SOCIOECONOMIC DISADVANTAGE, SOCIAL ISOLATION
Od
ds
Ra
tios
No Adverse Childhood Experience (n=502)1 Adverse Childhood Experience (n=253)2+ Adverse Childhood Experiences (n=98)
00
.51
1.5
22
.53
3.5
44
.55
![Page 36: Adverse Childhood Experiences and the Origins of Adult Disease Evidence from the Dunedin Study](https://reader035.vdocument.in/reader035/viewer/2022070403/568139d4550346895da18832/html5/thumbnails/36.jpg)
Danese A et al (submitted)
CHILD EXPERIENCES AND ADULT HEALTH
PANEL B:
Od
ds
Ra
tios
No Adverse Childhood Experience (n=502)1 Adverse Childhood Experience (n=253)2+ Adverse Childhood Experiences (n=98)
00
.51
1.5
22
.53
3.5
44
.55
hsCRP>3 mg/L
MALTREATMENT, SOCIOECONOMIC DISADVANTAGE, SOCIAL ISOLATION
![Page 37: Adverse Childhood Experiences and the Origins of Adult Disease Evidence from the Dunedin Study](https://reader035.vdocument.in/reader035/viewer/2022070403/568139d4550346895da18832/html5/thumbnails/37.jpg)
Danese A et al (submitted)
CHILD EXPERIENCES AND ADULT HEALTH
PANEL A: PANEL B:
Od
ds
Ra
tios
No Adverse Childhood Experience (n=502)1 Adverse Childhood Experience (n=253)2+ Adverse Childhood Experiences (n=98)
00
.51
1.5
22
.53
3.5
44
.55
Major hsCRPdepression >3 mg/L
MALTREATMENT, SOCIOECONOMIC DISADVANTAGE, SOCIAL ISOLATION
![Page 38: Adverse Childhood Experiences and the Origins of Adult Disease Evidence from the Dunedin Study](https://reader035.vdocument.in/reader035/viewer/2022070403/568139d4550346895da18832/html5/thumbnails/38.jpg)
Danese A et al (submitted)
CHILD EXPERIENCES AND ADULT HEALTH
PANEL A: PANEL B: PANEL C:
Od
ds
Ra
tios
No Adverse Childhood Experience (n=502)1 Adverse Childhood Experience (n=253)2+ Adverse Childhood Experiences (n=98)
00
.51
1.5
22
.53
3.5
44
.55
Major hsCRP Clustering ofdepression >3 mg/L metabolic risk
markers
MALTREATMENT, SOCIOECONOMIC DISADVANTAGE, SOCIAL ISOLATION
![Page 39: Adverse Childhood Experiences and the Origins of Adult Disease Evidence from the Dunedin Study](https://reader035.vdocument.in/reader035/viewer/2022070403/568139d4550346895da18832/html5/thumbnails/39.jpg)
Danese A et al (submitted)
CHILD EXPERIENCES AND ADULT HEALTH
PANEL A: PANEL B: PANEL C: PANEL D:
Od
ds
Ra
tios
No Adverse Childhood Experience (n=502)1 Adverse Childhood Experience (n=253)2+ Adverse Childhood Experiences (n=98)
00
.51
1.5
22
.53
3.5
44
.55
Major hsCRP Clustering of 1 or moredepression >3 mg/L metabolic risk risks
markers
MALTREATMENT, SOCIOECONOMIC DISADVANTAGE, SOCIAL ISOLATION
![Page 40: Adverse Childhood Experiences and the Origins of Adult Disease Evidence from the Dunedin Study](https://reader035.vdocument.in/reader035/viewer/2022070403/568139d4550346895da18832/html5/thumbnails/40.jpg)
Danese A et al (submitted)
CHILD EXPERIENCES AND ADULT HEALTH
PANEL A: PANEL B: PANEL C: PANEL D:
Od
ds
Ra
tios
No Adverse Childhood Experience (n=502)1 Adverse Childhood Experience (n=253)2+ Adverse Childhood Experiences (n=98)
00
.51
1.5
22
.53
3.5
44
.55
Major hsCRP Clustering of 1 or moredepression >3 mg/L metabolic risk risks
markers
MALTREATMENT, SOCIOECONOMIC DISADVANTAGE, SOCIAL ISOLATION
> DEVELOPMENTAL:
family history,
birth weight,
child BMI
![Page 41: Adverse Childhood Experiences and the Origins of Adult Disease Evidence from the Dunedin Study](https://reader035.vdocument.in/reader035/viewer/2022070403/568139d4550346895da18832/html5/thumbnails/41.jpg)
Danese A et al (submitted)
CHILD EXPERIENCES AND ADULT HEALTH
PANEL A: PANEL B: PANEL C: PANEL D:
Od
ds
Ra
tios
No Adverse Childhood Experience (n=502)1 Adverse Childhood Experience (n=253)2+ Adverse Childhood Experiences (n=98)
00
.51
1.5
22
.53
3.5
44
.55
Major hsCRP Clustering of 1 or moredepression >3 mg/L metabolic risk risks
markers
> DEVELOPMENTAL:
family history,
birth weight,
child BMI
> CURRENT:
SES,
smoking,
physical activity,
diet
MALTREATMENT, SOCIOECONOMIC DISADVANTAGE, SOCIAL ISOLATION
![Page 42: Adverse Childhood Experiences and the Origins of Adult Disease Evidence from the Dunedin Study](https://reader035.vdocument.in/reader035/viewer/2022070403/568139d4550346895da18832/html5/thumbnails/42.jpg)
SUMMARY (3)> Different adverse childhood experiences do not necessary overlap, and should be tackled independently.
> Adverse childhood experiences influence the development of different stress-sensitive systems.
> The effect of adverse childhood experiences on stress-sensitive system is independent from established (and less preventable) developmental and adult risk factors.
![Page 43: Adverse Childhood Experiences and the Origins of Adult Disease Evidence from the Dunedin Study](https://reader035.vdocument.in/reader035/viewer/2022070403/568139d4550346895da18832/html5/thumbnails/43.jpg)
introduction
enduring effects of child stress
timing matters
developing allostatic load
> conclusions
![Page 44: Adverse Childhood Experiences and the Origins of Adult Disease Evidence from the Dunedin Study](https://reader035.vdocument.in/reader035/viewer/2022070403/568139d4550346895da18832/html5/thumbnails/44.jpg)
01
02
03
04
0
No Probable Definite
Childhood maltreatment
hsC
RP
> 3
mg
/L (
%)
CONCLUSIONS
> Inflammation could be an important biological mediator of the effect of childhood maltreatment on adult health.
Danese A et al, PNAS 2007, 104:1319-24
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010
2030
4050
Controls Depressed-only Maltreated-only Depressed+maltreated
hsC
RP
> 3
mg/
L (%
)
(N=673) (N=109) (N=56) (N=27)
* *
CONCLUSIONS
> Effective preventive strategies for adult disease should start from an early age.
Danese A et al, Arch Gen Psychiatry 2008, 65: 409-15
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> The promotion of healthy psychosocial experiences for children is a necessary, and potentially cost-effective, target for the disease prevention.
CONCLUSIONS
Danese A et al (submitted)
PANEL A: PANEL B: PANEL C: PANEL D:
Od
ds
Ra
tios
No Adverse Childhood Experience (n=502)1 Adverse Childhood Experience (n=253)2+ Adverse Childhood Experiences (n=98)
00
.51
1.5
22
.53
3.5
44
.55
Major hsCRP Clustering of 1 or moredepression >3 mg/L metabolic risk risks
markers
![Page 47: Adverse Childhood Experiences and the Origins of Adult Disease Evidence from the Dunedin Study](https://reader035.vdocument.in/reader035/viewer/2022070403/568139d4550346895da18832/html5/thumbnails/47.jpg)
ACKNOWLEDGEMENT
Avshalom Caspi
Temi Moffitt
Carmine Pariante
Peter McGuffin
Dunedin, TEDS-Environment, & SPI Teams
Social, Genetic and Developmental
Psychiatry Centre
Stress, Psychiatry and Immunology Laboratory
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“The past is not dead. In fact, it is not even past”
W. Faulkner