putting the pieces together again: genes, child ......putting the pieces together again: genes,...

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