putting the pieces together again: genes, child ......putting the pieces together again: genes,...
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Putting the pieces together again: genes, child maltreatment and psychoanalysis
The 33rd Annual Daniel S. Prager Lecture David Reiss, MD
Yale Child Study Center May 1, 2014
Robert Plomin
Comparison of MZ (identical) and DZ (fraternal) twins: comparing heights within twin pairs
(contrived data)
1.00
.50
Sibling A
Sibl
ing
B
Sibl
ing
B
Sibling A
MZ twins DZ twins
Summary of data from Plomin’s studies Twins reared together (T) and Apart (A)
MZ= monozygotic DZ = dizygotic
00.10.20.30.40.50.60.70.80.9
1
MZT MZA DZT DZA Unrel sib
Cor
rela
tion
coef
ficie
nts
Summary of Plomin’s data
00.10.20.30.40.50.60.70.80.9
1
MZT MZA DZT DZA Unrel sib
Cor
rela
tion
coef
ficie
nts
Between-sibling differences: Nonshared environment + error
Between-family differences: Shared environment
Summary of Plomin’s data
00.10.20.30.40.50.60.70.80.9
1
MZT MZA DZT DZA Unrel sib
Cor
rela
tion
coef
ficie
nts
Shared family en: SES, Neighborhood decay, maternal depression
MIRROR IMAGE TWIN STUDIES: Adolescents-as-twins study (NEAD) vs parents-as-twins study (TOSS)
A
F M
A
Sib type (A-A) Genetic relatedness 93 MZ 100% 99 DZ 50% 95 FS-non div 50% 182 FS-step 50% 109 HS-step 25% 130 Blended step 0%
A
Parent
A
Sib type (P -P) Genetic relatedness 254 MZ moms 100% 284 DZ moms 50% 128 MZ dads 100% 183 DZ dads 50%
Parent Spouse Spouse
MIRROR IMAGE TWIN STUDIES: Adolescents-as-twins study (NEAD) vs parents-as-twins study (TOSS)
A
F M
A
Sib type (A-A) Genetic relatedness 93 MZ 100% 99 DZ 50% 95 FS-non div 50% 182 FS-step 50% 109 HS-step 25% 130 Blended step 0%
A
Parent
A
Sib type (P -P) Genetic relatedness 254 MZ moms 100% 284 DZ moms 50% 128 MZ dads 100% 183 DZ dads 50%
Parent Spouse Spouse
Adolescent antisocial behavior
Disruptive, rude, aggressive, coercive behavior
Trouble in school, skipped school mean, bully.
Stole, lied, cheated
OBSERVER CODE PARENT AND CHILD REPORT
brief, in home video
school behavior
home and neighborhood
Illustration of within sib pair correlations for estimating genetic influence on antisocial behavior
Sibling A Sibling B
B’s anti- social behavior
A’s anti- social behavior
A’s anti- social behavior
B’s anti- social behavior
MZ
DZ
Antisocial behavior: Mother, father, child and observer reports Numbers on vertical axis are intraclass correlations within sibships
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
MZ DZ Full-ND Full-step Half-step Blended-step
Heritability = 67% Environmentality: Shared = 12% Nonshared = 21%
Parent-child negativity:
Anger and rejection Coercion Conflict
Disagreement Punitiveness Yielding to coercion Open conflict Verbal aggression
OBSERVER CODES PARENT AND CHILD REPORT
Illustration of within sibling correlations for detecting genetic influences on mother’s negativity
Sibling A Sibling B MZ
DZ
mother’s negativity to sib A
mother’s negativity to sib B
mother’s negativity to sib A
mother’s negativity to sib B
Mother’s negativity towards child: within sibship correlations across sibling types. Numbers on vertical axis are intraclass correlations within sibships
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
MZ DZ Full-ND Full-step Half-step Blended-stepHeritability = 59%
Environmentality: Shared = 15% Nonshared = 26%
Illustration of cross-variable, within-sib pair correlations for detecting overlap of genetic
influences Sibling A Sibling B
mother’s negativity to sib A
mother’s negativity to sib B
B’s anti- social behavior
A’s anti- social behavior
Overlapping genetic influences on mother’s negativity and adolescent antisocial behavior: comparing cross variable, within sib pair correlations
0
0.1
0.2
0.3
0.4
0.5
0.6
corr
elat
ion
MZ twins DZ twins Full-ND Full-step Half-step Blended-step
phenotypic correlation = .59 68% of this corr. is attributable to G
r = .59
27% of this corr. is attributable to SE
Evocative gene-environment correlations: null hypothesis, family effects and child effects versions
Adolescent antisocial behavior
Ga
Mother-child negative interaction
child evokes
parent influences
FAMILY EFFECTS
CHILD EFFECTS
(heritable & evocative child characteristic)
NULL HYPOTHESIS
Early Growth & Development Study n=361 expanded to n = 561
Birth Mother
Adopted Child
Birth Father
Adoptive Mother
Adoptive Father
ADOPTED CHILDREN
Genetic Influences
Environmental Influences
BIRTH PARENTS
SUDs and related disorders
Externalizing and internalizing problems
ADOPTIVE PARENTS
Parenting in the context of depression, marital problems and economic worries
Early Growth & Development Study
Birth Mother
Adopted Child
Birth Father
Adoptive Mother
Adoptive Father
ADOPTED CHILDREN
Genetic Influences
Environmental moderation
BIRTH PARENTS
SUDs and related disorders
Externalizing and internalizing problems
ADOPTIVE PARENTS
Parenting in the context of depression, marital problems and economic worries
Photo Source: Strategies for Success (Chandler, AZ), 2012
I can’t understand my baby I can’t make my baby look at me I don’t know what games and toys my baby likes My kid struggles over bed time Baby sitters are hard to find Always cleaning up messes of toys and food When my child misbehave I raise my voice and yell When I am under stress I am picky and on my child’s back Items slightly paraphrased from D. S. Arnold (1993), KA Crnic (1990) and DM Teti (1991)
Early Growth & Development Study
Birth Mother
Adopted Child
Birth Father
Adoptive Mother
Adoptive Father
ADOPTED CHILDREN
Internalizing and externalizing problems
Genetic Influences
Environmental Influences
BIRTH PARENTS: SUDs and related disorders
Evocative influences
ADOPTIVE PARENTS
Parenting in the context of depression, marital problems and economic worries
Prospective adoption study
BM BF
Adoptive Parents in ADVERSE CONTEXT
AM BF
AC
BM BM BF AM BF
AC
BM
Adoptive Parents in FAVORABLE CONTEXT
Child’ high and low genetic risk for externalizing disorders
Contrived data
14
13
12
Chi
ld e
xter
naliz
ing
prob
lem
s
-1 -.5 0 .5 1 adoptive parents’ hostile parenting
and adoptive parents’ hostile parenting
BM low externalizing
BM high externalizing
Children high and low genetic risk for externalizing disorders and adoptive parents’ marital satisfaction (n = 561)
both 9 mos.
Source: P. Fearon, submitted
3
2
1
mat
erna
l vex
atio
n
-2 -.1 0 1.0 1 adoptive parents’ marital distress
BM low externalizing
BM high externalizing
Birth mother externalizing
Marital distress
BM externalizing x Marital distress
Adoptive mother vexation (9-27 mos.)
Child behavior Problems (27 mos.)
.03
.23
.16
.42
David Barker 1938-2013
Long term impact of restricted fetal growth: Standardized mortality ratios due to ischemic heat disease and chronic,
obstructive pulmonary disease 7991 men born in Hertfordshire between 1911-1930
source: DJP Barker et al 1989
0
20
40
60
80
100
120
<5.5 6-6.5 7-7.5 8-8.5 9-9.5 >10
Ischemic heart diease
Obstructive lungdisease
Birth weight (pounds)
Stan
dard
ized
mor
talit
y ra
tio
Critical evidence for programming: the added risk of “catch-up” growth for death from coronary artery disease
3641 men born in Helsinki between 1924 and 1933 source JG Eriksson, DJP Barker et al 1999
Ponderal index (kg/m3) at BIRTH
Bod
y m
ass
inde
x (k
g/m
2) a
t 11Y
EAR
S
Hazard ratios (deaths/unit time compared to Finnish avg. for age and birth year)
Source: JG Erikson, 1999
Confirmation of the effects of fetal growth restriction in a rat model: birth weight and adult (12 week) systolic BP
source : MF Shreuder et al, 2006
Birth weight (grams)
Syst
olic
BP
(mm
Hg)
Low birth weight and depression in teenage girls (n= 1420) n=81 low birth weight( < 5.5 lbs)
Source: Great Smoky Mountain Study EJ Costello, 2007
(Post natal sexual abuse, physical abuse neglect, parental mental illness, stressful events)
Girls with LOW Birth weight
Girls with HIGH Birth weight
Caroline Bedell Thomas, MD 1904-1997
Johns Hopkins Medical School Class of 1951
Cumulative probability of coronary heart disease (MH, angina or other CHD): 1131 white, male Hopkins med students with annual follow-up
(The Johns Hopkins Precursor Study Caroline Thomas original PI JHMS Classes of 1948-1961
Age in years
Cum
ulat
ive
mor
bidi
ty, %
High SES
Low SES
source MM Kittleson, 2006
Prospective study of childhood adversity before 11 and adult risk of illness at age 32: 972 in the Dunedin, NZ study
source A. Danese T Moffitt, 2009
0
0.5
1
1.5
2
2.5
Low SES(19.7%)
Definitemaltreatment
(9.6%)
Severe socialisolation (25%)
Depression
CRP . Mg/l
metabolic risk (seenote)
Note: At least 3 of 1) overwt; 2)hi BP; 3)hi cholest.; 4) lo high density LP; 5)hi HbA1c; 6) low 02 consumption
Controls: •Fam Hx cardiovasc • and dep •Birth wt •Childhood BMI •Current SES •Current smoking •Currenjt physical activity •Current diet •Current meds
Documented child abuse and neglect before age 11 and objective signs of illness risk at age 40
source: C Widom 2012
00.5
11.5
22.5
33.5
44.5
phyisicalabuse (57)
sexual abuse(47)
neglect (275)
HBa1c > 6%
Malnutrition(BMI/lymphocyte/albumin)
*
*
**
*
* ** p < .05 p < .01 in comparisons to 237 controls
Controls: •age •gender •race •childhood SES •adult SES •smoking •substance abuse •depression/PTSD
Stephen Suomi
Experimental assignment to rearing conditions: health outcomes source: S. Suomi and colleagues (see Conti, G Suom S, Heckman J et al, 2012)
Timeline Actual 37d 10-11 mos. 2 – 7 years
Human 4 mos. 3 years 6-21 years equiv
Nur
sery
rear
ed
Mot
her r
earin
g c
ontin
ued
Group housing Observations of impaired medical and behavioral health
Early childhood adversity and subsequent illness source: Conti, G et al 2012
Mother peer surrogate* Mother peer surrogate*
Mother peer surrogate* Mother peer surrogate*
* Peer exposure 2 hr/d in first year
Elissa Epel
Telomerase
39 care giving mothers 19 mothers of healthy children
Telomere length
Telomerase levels
no child maltreatment child maltreatment
Telomere length and adult reports of maltreatment “when I was growing up.”
Source: A Tryka, 2010
Genomic DNA
Primary transcript (RNA)
Mature transcript (RNA)
Protein
Promoter Exon Intron
Experimental assignment to rearing conditions: health outcomes source: S. Suomi and colleagues (see Conti, G Suom S, Heckman J et al, 2012)
Timeline Actual 37d 10-11 mos. 2 – 7 years
Human 4 mos. 3 years 6-21 years equiv
Nur
sery
rear
ed
Mot
her r
earin
g c
ontin
ued
Group housing Observations of impaired medical and behavioral health
Mother reared
Peer reared
717 521
Inflammation Cell growth/differentiation
Transcription control
Immunoglobulin production Type I interferon antiviral response
Suomi
Early life social conditions S.
Down regulated
Up regulated
Adolescent Twin Study Robert Plomin, IOP (UK) Mavis Hetherington, UVa Jenae Neiderhiser, Penn State Jody Ganiban, GWU Adoption Study Leslie Leve, U Oregon Jenae Neiderhiser, Penn State Danny Shaw, Pitt Jody Ganiban, GWU Pasco Fearon UCL (UK) NIH/NIA Project on early adversity (“Reversibility”) Stephen Suomi, NICHD Richard Suzman, NIA/BSR Lisbeth Nielsen, NIA/BSR
Maternal negative and and adolescent antisocial behavior: contemporaneous analysis at age 12.5
A
Maternal negativity
Adolescent antisocial behavior
a c
C
e
.77 .52
.49 .32
Common genetic influence on association between prior parenting and subsequent antisocial behavior (controlling for stability, contemporaneous associations and
adolescent asb -> maternal negativity)
A
Maternal negativity
Adolescent antisocial behavior
.39 .45
11.5 14.5 mean age of adolescent
a
The relationship between child temperament and maternal negativity and conflict
0102030405060708090
100
Perturbed parent
LOW negative emotionality HIGH
Varia
nce
of m
n at
tribu
tabl
e to
G (u
nsta
ndar
dize
d)
Source: J Ganiban, 2011
Imperturbable parent
LO Directly observed parental behavior HI
LO P
ropo
rtio
n of
gen
etic
influ
ence
HI
on a
ntis
ocia
l beh
avio
r
Harsh parenting
Warm parenting
Source: M. Feinberg, Arch. Gen. Psychiat., 2007
Parental behavior and expression of genetic influence on antisocial behavior
these include the imperturbable parents
LO Marital satisfaction HI
LO P
ropo
rtion
of g
enet
ic in
fluen
ce H
I
on
mat
erna
l neg
ativ
ity
Source: J. Ulbricht, 2013
Parental behavior and expression of genetic influence on disinhibited behavior
Adoptive Mother
ADHD sx
Child ADHD sx (father
report)
Adoptive Mother-to-
Child Hostility
Child Impulsivity/ Activation
Biological Mother
ADHD sx
.28** .16*
.17**
Evocative rGE on Child ADHD Symptoms
.24**
.23**
.17*
Genetically Related Genetically Unrelated -.05
-.05
.03
27 months 4.5 years 6 years
(G .Harold et al., JCPP in press)
-0.4
-0.3
-0.2
-0.1
0
0.1
0.2
0.3
0.4
0.5
0.6
-1.9
3-1
.73
-1.5
2-1
.31
-1.1
1-0
.90
-0.6
9-0
.49
-0.2
8-0
.07
0.14
0.34
0.55
0.76
0.96
1.17
1.38
1.58
1.79
2.00
2.20H
igh
Chi
ld S
elf s
ooth
ing*
Low
Low Adoptive Mother depression/anxiety High
**
Child’s genetic risk for SUDs and mother’s depression/anxiety n = 361
Source L. Leve, Child Develop. ‘10 *Attention frustration task
9 mos.
BM low externalizing
BM high externalizing
40
42
44
46
48
50
52
54
1.00
6.65
12.3
017
.95
23.6
029
.25
34.9
040
.55
46.2
051
.85
57.5
063
.15
68.8
074
.45
80.1
085
.75
91.4
097
.05
102.
7010
8.35
114.
00
Low
Chi
ld B
ehav
ior P
robl
ems
Tot
al C
BC
Hig
h
Low Adoptive mother structured parenting* High
BM low disinhibition+ dep/anx
BM high disinhibtion+ dep/anx
**
Source: L Leve, JAACAP, 2009 * Coded videotape
+
9 - 18 mos.
risk for SUD (+) & adopted mothers structured parenting (n = 361)
40
42
44
46
48
50
52
11.0
016
.10
21.2
026
.30
31.4
036
.50
41.6
046
.70
51.8
056
.90
62.0
067
.10
72.2
077
.30
82.4
087
.50
92.6
097
.70
102.
8010
7.90
113.
00
Chi
ld B
ehav
ior
Prob
lem
s - T
otal
CB
CL
Adoptive father structured parenting
BF lowinternalizing/externalizingBF highinternalizing/externalizing
*
Source: L Leve, JAACAP, 2009
risk for SUD (+) & adopted fathers structured parenting (n = 95)
Photo Source: Strategies for Success (Chandler, AZ), 2012
Photo Source: drugfree.org
Photo Source: child abuse weekly