David Reiss, George Washington University Medical Center
David Reiss, George Washington University Medical Center
David Reiss, George Washington University Medical Center
You also want an ePaper? Increase the reach of your titles
YUMPU automatically turns print PDFs into web optimized ePapers that Google loves.
Genetic expression outside the skin:<br />
Implications for prevention<br />
<strong>David</strong> <strong>Reiss</strong><br />
<strong>Center</strong> for Family Research,<br />
<strong>George</strong> <strong>Washington</strong> <strong>University</strong><br />
Society for Prevention Research<br />
May 30, 2007<br />
Note: Slides that are marked “unpublished” contain data<br />
that have not been peer reviewed and hence are<br />
particularly subject to additional analyses and amended<br />
interpretation
Dynamics of gene expression: a<br />
schema<br />
Heritable evocation effects<br />
*<br />
Translation<br />
#<br />
Transcription<br />
*<br />
#<br />
Genetic promoter region<br />
Polygenic effects<br />
Epigenetic programming region<br />
Evolution of<br />
problem<br />
behaviors
Twins<br />
Monozygotic (MZ)<br />
Dizygotic (DZ)
Comparison of MZ (identical) and DZ (fraternal)<br />
twins: comparing heights within twin pairs<br />
(contrived data)<br />
Sibling B<br />
1.00<br />
Sibling B<br />
.50<br />
Sibling A<br />
MZ twins<br />
Sibling A<br />
DZ twins
Plomin’s summary of surprising findings on personality in<br />
the mid 80s (Swedish Adoption/Twin Study of Aging—SATSA)<br />
Correlation coefficients<br />
1<br />
0.9<br />
0.8<br />
0.7<br />
0.6<br />
0.5<br />
0.4<br />
0.3<br />
0.2<br />
0.1<br />
0<br />
MZT = monozygotic reared together<br />
MZA = monozygotic twins reared apart<br />
DZT = dizygotic twins reared together<br />
DZA = dizygotic twins reared apart<br />
MZT MZA DZT DZA Unrel sib
Correlation coefficients<br />
1<br />
0.9<br />
0.8<br />
0.7<br />
0.6<br />
0.5<br />
0.4<br />
0.3<br />
0.2<br />
0.1<br />
0<br />
Plomin’s summary (2)<br />
Between-sibling differences:<br />
Nonshared environment + error<br />
Between-family differences:<br />
Shared environment<br />
MZT MZA DZT DZA Unrel sib
Correlation coefficients<br />
1<br />
0.9<br />
0.8<br />
0.7<br />
0.6<br />
0.5<br />
0.4<br />
0.3<br />
0.2<br />
0.1<br />
0<br />
Plomin’s summary (3)<br />
Shared family en: SES,<br />
Neighborhood decay,<br />
maternal depression<br />
MZT MZA DZT DZA Unrel sib
Robert Plomin,<br />
Institute of Psychiatry, King’s<br />
College, London<br />
Mavis Hetherington,<br />
<strong>University</strong> of Virginia
Nonshared Environment in Adolescent<br />
Development (NEAD)<br />
M<br />
A<br />
A<br />
F<br />
Sib type (A-A) Genetic related.<br />
93 MZ 100%<br />
99 DZ 50%<br />
95 FS-non div 50%<br />
182 FS-step 50%<br />
109 HS-step 25%<br />
130 Blended step 0%<br />
Time 1 Time 2<br />
Child age 11.5 14.5
Adolescent antisocial behavior<br />
OBSERVER CODE<br />
PARENT AND CHILD<br />
REPORT<br />
Disruptive, rude,<br />
Trouble in school,<br />
aggressive, coercive<br />
skipped school mean,<br />
behavior school behavior bully.<br />
Stole, lied, cheated<br />
brief, in home video<br />
home and neighborhood
Illustration of within sib pair correlations for<br />
estimating genetic influence on antisocial behavior<br />
MZ<br />
Sibling A<br />
A’s antisocial<br />
behavior<br />
Sibling B<br />
B’s antisocial<br />
behavior<br />
DZ<br />
A’s antisocial<br />
behavior<br />
B’s antisocial<br />
behavior
Antisocial behavior: Mother, father, child and<br />
observer reports<br />
Numbers on vertical axis are intraclass correlations within sibships<br />
0.8<br />
0.7<br />
0.6<br />
0.5<br />
0.4<br />
0.3<br />
0.2<br />
0.1<br />
0<br />
MZ DZ Full-ND Full-step Half-step Blendedstep<br />
Heritability = 67%<br />
Environmentality: Shared = 12% Nonshared = 21%
Parent-child negativity:<br />
OBSERVER CODES<br />
Anger and rejection<br />
Coercion<br />
Conflict<br />
PARENT AND CHILD<br />
REPORT<br />
Disagreement<br />
Punitiveness<br />
Yielding to coercion<br />
Open conflict<br />
Verbal aggression
Illustration of within sibling correlations for<br />
detecting genetic influences on mother’s negativity<br />
MZ<br />
Sibling A<br />
mother’s<br />
negativity<br />
to sib A<br />
Sibling B<br />
mother’s<br />
negativity<br />
to sib B<br />
DZ<br />
mother’s<br />
negativity<br />
to sib A<br />
mother’s<br />
negativity<br />
to sib B
Mother’s negativity towards child: ACTUAL within<br />
sibship correlations across sibling types.<br />
Numbers on vertical axis are intraclass correlations within sibships<br />
0.8<br />
0.7<br />
0.6<br />
0.5<br />
0.4<br />
0.3<br />
0.2<br />
0.1<br />
0<br />
MZ DZ Full-ND Full-step Half-step Blendedstep<br />
Heritability = 59%<br />
Environmentality: Shared = 15% Nonshared = 26%
A simple schema of parent-child relationship<br />
Maternal conflict<br />
and negativity<br />
Child<br />
antisocial<br />
behavior<br />
Child<br />
evocative<br />
behavior<br />
G a<br />
G a
A simple schema of parent-child relationship<br />
Maternal conflict<br />
and negativity<br />
Child<br />
antisocial<br />
behavior<br />
.59<br />
Child<br />
evocative<br />
behavior<br />
G as<br />
G m
Illustration of cross-variable, within-sib pair<br />
correlations for detecting overlap of genetic<br />
influences<br />
Sibling A<br />
Sibling B<br />
mother’s<br />
negativity<br />
to sib A<br />
mother’s<br />
negativity<br />
to sib B<br />
A’s antisocial<br />
behavior<br />
B’s antisocial<br />
behavior
Schematic illustrating cross correlation<br />
MZ twins (100%) Blended sibs (0%)<br />
mn as<br />
mn as<br />
mn as<br />
1 1<br />
mn as<br />
mn as<br />
mn as<br />
1 0<br />
1 1<br />
0 1<br />
mn as<br />
mn as<br />
0 0<br />
mn as<br />
mn as<br />
0 1<br />
0 0<br />
1 0<br />
mn = maternal negativity as=antisocial behavior
Illustration of cross-variable, within-sib pair<br />
correlations for detecting overlap of genetic<br />
influences<br />
Sibling A<br />
Sibling B<br />
mother’s<br />
negativity<br />
to sib A<br />
mother’s<br />
negativity<br />
to sib B<br />
A’s antisocial<br />
behavior<br />
B’s antisocial<br />
behavior
Overlapping genetic influences on mother’s<br />
negativity and adolescent antisocial behavior:<br />
comparing cross variable, within sib pair correlations<br />
WHAT WE EXPECTED TO FIND<br />
0.6<br />
0.5<br />
r = .59<br />
correlation<br />
0.4<br />
0.3<br />
0.2<br />
0.1<br />
0<br />
MZ twins DZ twins Full-ND Full-step Half-step Blendedstep<br />
phenotypic correlation = .59 >50% of this is attributable to NS
Overlapping genetic influences on mother’s<br />
negativity and adolescent antisocial behavior:<br />
comparing cross variable, within sib pair correlations<br />
0.6<br />
r = .59<br />
0.5<br />
correlation<br />
0.4<br />
0.3<br />
0.2<br />
0.1<br />
0<br />
MZ twins DZ twins Full-ND Full-step Half-step Blendedstep<br />
phenotypic correlation = .59 69% of this is attributable to G
Evocative gene-environment correlations: family<br />
effects and child effects versions<br />
Mother-child<br />
negative interaction<br />
FAMILY<br />
EFFECTS<br />
parent/ sib<br />
influences<br />
child evokes<br />
(heritable & evocative<br />
Child characteristic)<br />
Adolescent<br />
antisocial<br />
behavior<br />
CHILD<br />
EFFECTS<br />
G a
Relationships and development: longitudinal study<br />
of mother’s negativity and adolescent adjustment<br />
(J. Neiderhiser, Developmental Psychology, 35, 680, 1999)<br />
Earlier adolescence<br />
Later adolescence<br />
Mother-child<br />
negative<br />
interaction<br />
.15<br />
Mother-child<br />
negative<br />
interaction<br />
Adolescent antisocial<br />
behavior<br />
.08<br />
Adolescent antisocial<br />
behavior
Relationships and development: longitudinal study<br />
of father negativity and adolescent adjustment<br />
(J. Neiderhiser, Developmental Psychology, 35, 680, 1999)<br />
Earlier adolescence<br />
Later adolescence<br />
Father-child<br />
negative<br />
interaction<br />
.18<br />
Father-child<br />
negative<br />
interaction<br />
Adolescent antisocial<br />
behavior<br />
.03<br />
Adolescent antisocial<br />
behavior
A simple schema of parent-child relationship<br />
Maternal conflict<br />
and negativity<br />
Child<br />
antisocial<br />
behavior<br />
Child<br />
evocative<br />
behavior<br />
G a
A simple schema of parent-child relationship<br />
Maternal conflict<br />
and negativity<br />
Child<br />
antisocial<br />
behavior<br />
prevention target<br />
Child<br />
evocative<br />
behavior<br />
G a<br />
Source: J Ganiban, submitted<br />
•Emotionality<br />
cries easily<br />
easily upset<br />
intense reaction<br />
fusses<br />
•Activity<br />
•Sociability (-)
Variance of mn attributable to G (unstandardized)<br />
The relationship between child temperament and<br />
maternal negativity and conflict<br />
100<br />
90<br />
80<br />
70<br />
60<br />
50<br />
40<br />
30<br />
20<br />
10<br />
0<br />
Source: J Ganiban, unpublished<br />
Reactive parent<br />
Non-reactive parent<br />
LOW negative emotionality HIGH<br />
(with g corr of mn and emot partialed out)
Parental “reactivity”<br />
reactive<br />
Child persistently<br />
emotional and<br />
aggressive<br />
non-reactive<br />
Parent critical, hostile.<br />
yielding to coercion<br />
Parent resisting coercion<br />
warm, supportive
Parental behavior and expression of genetic influence<br />
on antisocial behavior<br />
LO Proportion of genetic influence HI<br />
on antisocial behavior<br />
Source: M. Feinberg, Arch. Gen. Psychiat., 2007<br />
Harsh parenting<br />
these include the non-responsive parents<br />
Warm parenting<br />
LO Directly observed parental behavior HI
A simple schema of parent-child relationship<br />
Maternal conflict<br />
and negativity<br />
Child<br />
antisocial<br />
behavior<br />
prevention target<br />
Child<br />
evocative<br />
behavior<br />
G a<br />
Source: J Ganiban, submitted<br />
•Emotionality<br />
cries easily<br />
easily upset<br />
intense reaction<br />
fusses<br />
•Activity<br />
•Sociability (-)
Family subsystems: rich in genetic information<br />
Mom’s negativity<br />
Dad’s negativity<br />
Mom’s positivity<br />
Dad’s positivity<br />
Dad’s knowledge<br />
Dad’s attempted control<br />
Dad’s actual control<br />
Mom’s knowledge<br />
Mom’s attempted control<br />
Mom’s actual control<br />
Sibling’s positivity<br />
Sibling’s negativity<br />
Mom-dad conflict re child<br />
only 6 of 78 correlations show more<br />
genetic overlap than specificity
Does the relationship code translate into specific behavioral<br />
consequences<br />
Principal component FA (oblique rotation) of genetic correlations<br />
(J Loehlin, Child Development, 76:1104, 2005)<br />
Parental negativity<br />
Parental positivity<br />
Parental control<br />
Antisocial behavior<br />
Autonomy<br />
Depressive symptoms<br />
Cognitive agency<br />
Sociability<br />
Social responsibility<br />
Additive g correlations<br />
1 2 3<br />
Nonadditive g corr.<br />
4 5 6<br />
Positive loadings<br />
Negative loadings
Variance of mn attributable to G (unstandardized)<br />
The relationship between child temperament and<br />
maternal negativity and conflict<br />
100<br />
90<br />
80<br />
70<br />
60<br />
50<br />
40<br />
30<br />
20<br />
10<br />
0<br />
Source: J Ganiban, unpublished<br />
Shared<br />
environmental<br />
Genetic<br />
LOW negative emotionality HIGH
Nancy Pedersen<br />
Karolinska Institute<br />
Marianne Cederblad<br />
Lund <strong>University</strong><br />
Paul Lichtenstein<br />
Karolinska Institute<br />
Jenae Neiderhiser,<br />
<strong>George</strong> <strong>Washington</strong> U
TWIN AND OFFSPRING STUDY IN SWEDEN (TOSS):<br />
Comparison of parental and child ages with<br />
adolescent sib study (NEAD)<br />
M<br />
F<br />
F<br />
M<br />
M<br />
F<br />
A<br />
A<br />
A<br />
150 MZ Pairs<br />
176 DZ Pairs<br />
A<br />
NEAD Time 2 TOSS<br />
Mn age, child 1 16.2 + 2.1 15.3 + 2.3<br />
Mn age, child 2 14.7 + 1.9<br />
Mn age, mother 40.5 + 4.8 43.9 + 4.4<br />
Mn age, father 43.7 + 6.1 46.0 + 5.2
Parent-child negativity:<br />
OBSERVER CODES<br />
Anger and rejection<br />
Coercion<br />
Conflict<br />
PARENT AND CHILD<br />
REPORT<br />
Disagreement<br />
Punitiveness<br />
Yielding to coercion<br />
Open conflict<br />
Verbal aggression
Parent-child warmth and support<br />
OBSERVER CODES<br />
• Positive feelings and<br />
affection<br />
• Self confident<br />
expression of needs<br />
• Listening, explaining,<br />
eliciting<br />
• Comfort with own<br />
and others initiative<br />
PARENT AND CHILD<br />
REPORT<br />
• Closeness<br />
• Rapport<br />
• Pleasure in common<br />
activities<br />
• Overt signs of<br />
affection
Maternal warmth and support:<br />
0.5<br />
0.45<br />
0.4<br />
0.35<br />
0.3<br />
0.25<br />
0.2<br />
0.15<br />
0.1<br />
0.05<br />
0<br />
Mother's<br />
report<br />
Child's<br />
report<br />
Observer's<br />
coding<br />
MZ<br />
DZ
Mother-child negativity:<br />
0.45<br />
0.4<br />
0.35<br />
0.3<br />
0.25<br />
0.2<br />
0.15<br />
0.1<br />
0.05<br />
0<br />
Mother's<br />
report<br />
Child's<br />
report<br />
Observer's<br />
coding<br />
MZ<br />
DZ
Variance of mn attributable to G (unstandardized)<br />
The relationship between child temperament and<br />
maternal negativity and conflict<br />
100<br />
90<br />
80<br />
70<br />
60<br />
50<br />
40<br />
30<br />
20<br />
10<br />
0<br />
Sister-specific<br />
environmental<br />
effect<br />
Source: J Ganiban, unpublished<br />
Shared<br />
environmental<br />
marital<br />
conflict<br />
Genetic<br />
LOW negative emotionality HIGH
A simple schema of parent-child relationship<br />
ADOLESCENT MEAN AGE<br />
13 16<br />
Maternal conflict<br />
and negativity<br />
Maternal conflict<br />
and negativity<br />
Preventive<br />
intervention<br />
emotionality and<br />
aggression<br />
emotionality and<br />
aggression<br />
G a<br />
G a
Emotion,<br />
temperament<br />
& language<br />
Plomin et al.,<br />
1993<br />
Internalizing/<br />
Externalizing<br />
Haberstick, et al 2005<br />
Attention<br />
Rietveld, Hudziak 2004<br />
Change in genetic influences<br />
across the lifespan<br />
Antisocial behavior,<br />
sociability, social<br />
responsibility, autonomy<br />
<strong>Reiss</strong> et al., 2000<br />
Personality<br />
Viken et al.,<br />
1994<br />
Personality<br />
Johnson et al<br />
2004<br />
No change<br />
Change<br />
Personality<br />
Pedersen<br />
And Reynolds,<br />
1998<br />
Depression<br />
McGue, 2003<br />
Years2 4 6 10 18<br />
50 54<br />
60 68<br />
Behavior<br />
problems<br />
Van den Oord<br />
& Rowe, 1997<br />
Personality<br />
Gillespie et al<br />
2004<br />
Depression<br />
Kendler, et al.<br />
1993<br />
Cognition<br />
Plomin, et al,<br />
1994
Change in genetic influences<br />
across the lifespan<br />
Emotion,<br />
temperament<br />
& language<br />
Plomin et al.,<br />
1993<br />
Internalizing/<br />
Externalizing<br />
Haberstick, et al 2005<br />
Attention<br />
Rietveld, Hudziak 2004<br />
Antisocial behavior,<br />
sociability, social<br />
responsibility, autonomy<br />
<strong>Reiss</strong> et al., 2000<br />
Personality<br />
Viken et al.,<br />
1994<br />
No change<br />
Change<br />
Personality<br />
Pedersen<br />
And Reynolds,<br />
1998<br />
Years<br />
2 4 6 10 18<br />
50 54<br />
60 68<br />
Behavior<br />
problems<br />
Van den Oord<br />
& Rowe, 1997<br />
Depression<br />
Kendler, et al.<br />
1996<br />
Cognition<br />
Plomin, et al,<br />
1994
Jenae Neiderhiser,<br />
GWU<br />
PI, Prenatal follow-up<br />
Leslie Leve,<br />
Oregon Social Learning<br />
<strong>Center</strong>, Eugene<br />
PI, First grade follow-up<br />
Xiaojia Ge,<br />
UC Davis/U. Minnesota<br />
Laura Scaramella,<br />
U. Of New Orleans
Geographical distribution of birth parents and adoptive families<br />
132<br />
143<br />
1<br />
0<br />
0<br />
93<br />
10<br />
7<br />
22<br />
0<br />
2<br />
0<br />
2<br />
1<br />
2<br />
1<br />
2<br />
6<br />
8 2<br />
3<br />
1<br />
3<br />
0<br />
74<br />
37<br />
9<br />
3<br />
3<br />
0<br />
16<br />
7<br />
1<br />
3<br />
1<br />
2<br />
4<br />
13<br />
3<br />
8<br />
1 0<br />
CT = 1<br />
DC = 10<br />
DE = 7<br />
MA = 1<br />
MD = 59<br />
NJ = 12<br />
RI = 1<br />
0<br />
Outside United<br />
States<br />
France = 1<br />
11<br />
UC Davis OSLC GWU
Early Growth & Development Study (EGDS)<br />
Birth Parents Assessed @ 3 & 16<br />
months postpartum<br />
Temperament psychopathology and<br />
social competence<br />
Adoptive Parents Assessed @ 9,<br />
18 & 27 months<br />
Reactivity to child’s<br />
evocative behavior<br />
Birth<br />
Mother<br />
Birth<br />
Father<br />
Adoptive<br />
Mother<br />
Adoptive<br />
Father<br />
Environmental<br />
Influences<br />
Genetic Influences<br />
Adopted<br />
Child<br />
Children assessed @ 9,<br />
18 & 27 months<br />
Internalizing, externalizing<br />
and social competence
Prospective adoption study: wave I<br />
n= 357 “yoked” unit (BM, BF, AM, AF, AC)<br />
Adoptive Parents assessed at<br />
9 mos., REACTIVITY PRESENT<br />
Birth Parents Assessed @ 3 & 16<br />
months postpartum: temperament,<br />
psychopathology, substance use<br />
and social competence<br />
Adoptive Parents assessed at<br />
9 mos., REACTIVITY ABSENT<br />
BM BF AM AF<br />
BM BF AM AF<br />
AC<br />
AC<br />
Genetic Influences<br />
Genetic Influences<br />
Children assessed 9months<br />
Early appearing heritable<br />
risk factors (e.g. negative emotionality and<br />
attentional decay) and social competence
EGDS Prospective adoption study: unfolding of genetically<br />
influenced parent-child relationship<br />
Birth Parents Assessed at 3 and 16 months<br />
postpartum, temperament, psychopathology<br />
drug use and social competence<br />
Adoptive Parents Assessed at 9 Adoptive Parents Assessed at 9 &<br />
& 18 mos., REACTIVITY +<br />
18 mos., REACTIVITY -<br />
BM BF AM AF<br />
BM BF AM AF<br />
AC<br />
AC<br />
Genetic Influences<br />
Genetic Influences<br />
Parent-child relationship assessed<br />
at 9 and 18 and 27 monthmonths
Specific family preventive intervention and<br />
genetic expression:<br />
testing a theory with an adoption design<br />
Adopted child psychopathology<br />
Successful treatment with<br />
no effect on genetic<br />
expression<br />
control<br />
treatment<br />
Successful treatment with<br />
Substantial effect on<br />
genetic expression<br />
control<br />
treatment<br />
Birth parent psychopathology
The genetic prevention-intervention research cycle<br />
(with apologies to Rick Price)<br />
2<br />
Community-based pilots<br />
of intervention within genetically<br />
informed designs<br />
1<br />
Research on molecular<br />
and interpersonal mechanisms<br />
of genetic expression<br />
3<br />
Full scale, genetically-informed<br />
trial while monitoring processes<br />
of genetic expression<br />
4<br />
Reduction of genetic risk<br />
Improved understanding of mechanisms<br />
of genetic expression
A simple schema of parent-child relationship<br />
Maternal conflict<br />
and negativity<br />
Parenteddirected<br />
child behavior<br />
Emotionality<br />
Other studies<br />
• Ge, X 1996<br />
defiance, aggression,<br />
conduct problems<br />
• Burt, S. A. 2005<br />
temper, spiteful, conduct<br />
problems<br />
• Narusyte, J 2006<br />
aggression, irritability<br />
• Reprise of Olweus D, 1980<br />
G a