DIFFERENTIAL

SUSCEPTIBILITY TO

ENVIRONMENTAL INFLUENCES:

From Longitudinal

Research to Intervention

Part B

Jay Belsky

CAN WE MOVE BEYOND CORRELATIONAL EVIDENCE TO EXPERIMENTAL DATA?

OUTLINE MORNING

I. Observational Evidence A. Temperament B. Stress Physiology C. Highly Sensitive Person D. Candidate Genes E. Polygenic Approaches F. Mechanisms of Influence

G. Conclusions AFTERNOON

II. Experimental/Intervention Evidence

A. Temperament

B. Stress Physiology

C. Highly Sensitive Person

D. Candidate Genes

E. Polygenic Approaches

F. Conclusions

NEGATIVE EMOTIONALITY

Experimental Enhancement of Maternal Sensitivity via Circle of Security:

Effects on Attachment Security

Cassidy, J., et al. (2011). Enhancing infant attachment security: An examination of treatment efficacy and differential susceptibility. Development and Psychopathology.

Effect of Computerized (Phonemic) Literacy Instruction on Early Literacy Skills

Moderated by Mild Perinatal Adversities (Markers for negativity and physiological reactivity)

Van der Kooy-Hofland, V.A.C. et al. (2012). Differential susceptibility to early literacy intervention in children with mild perinatal adversities: Short- and long-term effects of a randomized control trial. Journal of Educational Psychology.

Grey:

Early perinatal

adversity.

White:

No early perinatal

adversity

Van den Bergy, H. & Bus, A.G. (2014). Beneficial effects of BookStart in temperamentally highly reactive infants. Learning and

Individual Differences, Volume 36, 2014, 69 - 75

Effects of Book-Exposure Intervention (8 months)

on Language Development (15 months)

Moderated by Temperamental Reactivity

BookStart Intervention Control Group

Highly Reactive

Low/Average Reactive

Intervention for Children with Conduct Disorder (Emotionally Dysregulated: loses temper, angry, touchy; Headstrong: Argues, defiant annoys, blames)

Scott, S. & O’Connor, T.G. (2012). An experimental test of differential susceptibility to parenting among emotionally dysregulated children in a Randomized Controlled Trial for Oppositional Behavior. Journal of Child Psychology and Psychiatry, 53, 1184-1193.

Change in conduct symptoms in children allocated to parenting

intervention compared to controls, by conduct disorder subtype

PHYSIOLOGICAL REACTIVITY

Intervention for Children with Disruptive Behavior Disorder (Cortisol Stress Reactivity: HS=Highly Reactive)

Van de Wiel et al. (2004). Cortisol and treatment effect in children with disruptive behavior disorder: A preliminary study. Journal of the American Academy of Child and Adolescent Psychiatry, 43, 1011-1018.

Pre- and postrtreament comparison of Parent Daily Report (PDR) Overt Aggression scores and Oppositional Behavior scores in high

cortisol stress responsivity (HS) and low cortisol stress responsivity (LS) in disruptive behavior disorder subgroups

HIGHLY SENSITIVE PERSON

Effects of School-Based Resilience Program (Sparks) on Girls’ Depression Moderated by HSP

Pluess, M., & Boniwell, I. (2015). Sensory-Processing Sensitivity Predicts Treatment Response to a School-Based Depression Prevention Program:

Evidence of Vantage Sensitivity. Personality and Individual Differences, 82, 40-45.

* *

NOT an

RCT

CANDIDATE GENES

5-HTTLPR

Experimental Enhancement of Maternal Sensitivity Via Home Visiting In South Africa from Pregnancy to 6 mos.: Effects on Attachment Security Moderated by 5-HTTLPR

Morgan, B. et al. (2017). Serotonin transporter gene (SLC6A4) polymorphism and susceptibility to a home-visiting maternal-infant attachment intervention delivered by community health Workers in South Africa: Re-analysis of a randomized controlled trial. PLOS Medicine

0

1

2

3

4

5

6

SS/SL LL

Od

ds

of

Secu

re A

ttac

hm

en

t

Controls

Intervention

GENOTYPE

Intervention Effects on Indiscriminant Social Behavior Among Institutionalized Romanian Children

Moderated by 5-HTTLPR (CAUG: Care as Usual Group; FCG: Foster Care Group)

Drury, S.S. et al. (2012). Genetic sensitivity to the caregiving context: The influence of 5httplor and BDNF val66 met on indiscriminant social behavior. Physiology and Behavior.

Effect of High-Quality Foster Care/Adoption of Institutionalized Children and Externalizing Problems

Moderated by 5-HTTLPR

Brett, Z.H. et al. (2015). Serotonin transporter linked polymorphic region (5-HTTLPR) genotype moderates the longitudinal impact of early caregiving on externalizing behavior. Development and Psychopathology, 27, 7-18.

Care As Usual Group:

Remained Institutionalized

Foster Care Group

CBCL externalizing

Eley, T.C. et al. (2012). Therapygenetics: The 5HTTLPR and response to psychological therapy. Molecular

Psychiatry, 17, 236-237.

CHILDREN’S RESPONSE TO CBT

MODERATED BY 5HTTLPR

(i) (ii)

(i) Proportion of children free of (a) their primary anxiety

disorder and (b) all anxiety disorders at follow-up by 5HTTLPR

genotype.

(ii) Symptom severity of primary diagnosis at each time point, as

a function of genotype.

Effect of Substance Abuse Prevention Program On Substance Use Initaition Moderated by 5-HTTLPR (see Panel D)

Schlomer, G.L. et al. (2016). Extending previous cGxI findings on 5-HTTLPR’s moderation of intervention effects on adolescent substance misuse initiation. Child Development.

Short-allele

controls show

most increase

in substance

use, with

prevention

only for short-

allele

intervention

adolescents

DRD4

Development of Externalizing Behavior for Intervention and Control Groups By DRD47-Repeat Allele

16

20

24

28

screening pretest posttest follow-up

7- control7+ control7- intervention7+ intervention

CBCL Externalizing

Bakermans-Kranenburg et al. (2008). Experimental evidence for differential susceptibility: Dopamine D4 receptor polymorphism (DRD4 VNTR) moderates intervention effects on toddlers' externalizing behavior in a randomized controlled trial. Developmental Psychology, 44, 293-300.

Effect of Computerized Literacy Instruction Emphasizing PHONEMIC AWARENESS

on Emergent Literacy Skills Moderated by DRD4-7R (Long)

Kegel, C., Bus, A. & Van IJzendoorn, M. (2011).Differential susceptibility in early literacy instruction through

computer games: The role of Dopamine D4 Receptor Gene (DRD4). Mind, Brain, and Education, 5, 71-79

Effect of Strong African American Families Program On Substance Use

Moderated by DRD4-7R (LEFT PANEL): Study I

Beach, S. et al. (2010). Differential susceptibility to parenting among African American Youths. Journal of Family Psychology, 24, 513-521.

BDNF

Effects of Meditation on Perceived Stress Moderated by BDNF

Jung, Y. et al. (2011). Inlfuence of brain-derived neurotrophic factor and catechol O-methyl transferase polymorphisms on effects of meditation on plasma catecholamines and stress. Stress.

Polygenic Moderation

Intervention Effects on Indiscriminant Social Behavior Among Institutionalized Romanian Children Moderated by Cumulative Genetic Plasticity: 5-HTTLPR and BDNF (CAUG: Care as Usual Group; FCG: Foster Care Group)

Drury, S.S. et al. (2012). Genetic sensitivity to the caregiving context: The influence of 5httplor and BDNF val66 met on indiscriminant social behavior. Physiology and Behavior, 106, 728-735.

EFFECTS OF INCREDIBLE YEARS ON REDUCTION IN BOYS’ EXTERNALIZING MODERATED BY POLYGENIC DOPAMINERGIC INDEX (DRD4, DRD2, DAT1, MAOA, and COMT)

Chhangur, R.R….. & Belsky, J. (2016). Genetic moderation of Intervention Efficacy: Dopaminergic genes, the Incredible Years, and externalizing

behavior in children. Child Development.

EFFECTS OF INCREDIBLE YEARS ON REDUCTION IN BOYS’ EXTERNALIZING MODERATED BY POLYGENIC DOPAMINERGIC INDEX and DEGREE OF PARENTAL CHANGE

Chhangur, R.R….. & Belsky, J. (2016). Genetic moderation of Intervention Efficacy: Dopaminergic genes, the Incredible Years, and externalizing

behavior in children. Child Development.

Intervention Effects on African-American Teens Alcohol Use Moderated by Multiple GABAergic and Dopaminergic Genes

Brody, G.H., Chen, Y., & Beach, S.R.H. (2013). Differential susceptibility to prevention: GABAergic, Dopaminergic, and multilocus effects. Journal of Child Psychology & Psychiatry, 54, 863-871

Effect of CBT Varieties (non-RCT) on CHANGE in Clinical Severity of Emotional Problems Moderated by GWAS-Derived Polygenic Environmental Sensitivity Score*

Keers, R. …..Eley, T. (2016). A genome-wide test of the differential susceptibility hypothesis reveals a genetic predictor of differential response to

psychological treaments for child anxiety disorders. Psychotherapy and Psychosomatics, 85, 146-158.

*Derived from independent sample of MZ twins who differed more vs. less than each other.

Most

Intensive

CBT

Least

Intensive

CBT

META-ANALYSIS OF GENE X INTERVENTION EFFECTS --22 experiments --involving 3,257 participants --with various developmental outcomes (e.g., externalizing problems, internalizing behaviors, cognitive development) --and various plasticity genes

META-ANALYTIC EFFECTS

Van Ijzendoorn, M.H., & Bakermans-Kranenburg, M. (in press). Genetic differential susceptibility on trial: Meta-analytic support from randomized controlled experiments. Development and Psychopathology.

-0.20

-0.10

0.00

0.10

0.20

0.30

0.40

macro micro nano

susceptible

non-susceptible

Macro: Broad, Multi-faceted intervention (e.g., Fast Track, Strong African-American

Families)

Micro: Narrow, mechanism-specific (e.g., phonemic awareness)

Nano: Immediate neural or behavioral responses to a small range of positive

and negative stimuli, to minor manipulations of stress levels, or to subtle

priming

CONCLUSIONS

--Implications for Intervention: Efficacy vs. Equity? --Pharmacological interventions for the less susceptible?