Does the social environment have a role to play in ADHD? Edmund Sonuga-Barke King s College London

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1 Does the social environment have a role to play in ADHD? Edmund Sonuga-Barke King s College London

2 Does the social environment have a role to play in the causes of ADHD? Edmund Sonuga-Barke King s College London

3 THE SOCIAL ECOLOGY OF HUMAN DEVELOPMENT

4 Does the family environment have a role to play in the causes of ADHD? Edmund Sonuga-Barke King s College London

5 BUT WHAT IS A FAMILY?

6 Does the rearing environment have a role to play in the causes of ADHD? Edmund Sonuga-Barke King s College London

7 RUNNING 0RDER ADHD is familial - shared G not shared rearing E. So why is ADHD linked to family adversity? Same G drive both E and child ADHD? Passive GE correlation. Child s G elicit E? Evocative GE correlation. Rearing experiences may still be important in combination with G. Beyond heritability Extraordinary non-family Es can cause ADHD. Can extraordinary therapeutic Es heal?

8 ADHD RUNS IN FAMILIES P Ch But why?

9 PARENTS PASS ON G AND CREATE REARING E G P Ch E Both are correlated with ADHD

10 PARENTS PASS ON G AND CREATE REARING E G P Ch CHILD ADHD E Both are correlated with ADHD

GENETIC MARKERS 106 MEMBERS, 14 COUNTRIES, 5 CONTINENTS 12

11 PGC ADHD/IPSYCH-SSI-BROAD COLLABORATION 20,183 CASES 35,191 ADHD AND CONTROLS, VARIATION 8,151,190 IN GENOME GENETIC MARKERS 106 MEMBERS, 14 COUNTRIES, 5 CONTINENTS 12 genome-wide significant loci All risk markers = 40% ADHD variance

12 DIFFICULT ADHD IS CIRCUMSTANCES MORE PREVALENT CLUSTER IN THOSE IN FAMILIES EDUCATIONAL UNDERACHIEVMENT SOCIAL DISADVANTAGE LESS HEALTHY LIFESTYLE DISCHORD & BREAKDOWN POOR MENTAL HEALTH DISORGANISED HOUSEHOLD FAMILY STRESS PARENTING CHALLENGES There is no simple story about what drives what?

13 ADHD IS MORE PREVALENT IN THOSE FAMILIES EDUCATIONAL UNDERACHIEVMENT SOCIAL DISADVANTAGE LESS HEALTHY LIFESTYLE DISCHORD & BREAKDOWN ADHD POOR MENTAL HEALTH DISORGANISED HOUSEHOLD FAMILY STRESS PARENTING CHALLENGES There is no simple story about what drives what? Small and non-deterministic and reciprocal associations.

14 PARENTS PASS ON G AND CREATE REARING E G P Ch CHILD ADHD E How can we know which is causing ADHD?

15 COMPARISON OF IDENTICAL AND NON-IDENTICAL TWINS Burt, MZ & DZ both share 100% of E but DZ share only 50% G.

16 G SEEMS THE MOST IMPORTANT G P CHILD Ch ADHD E But we still have those correlations with E to explain.

17 EXPLAINING ADHD REARING E CORRELATIONS

18 OPTION 1: PASSIVE GxE CORRELATION G P CHILD Ch ADHD E If true Child controlling ADHD for and G E should are driven remove by the same correlation genes with E.

19 PARENTAL LIFESTLYE EXAMPLE SMOKING 1 DURING PREGNANCY G M Ch CHILD ADHD E If Maternal causal, the smoking correlation during with pregnancy E should is be correlated present whatever with ADHD the genetic relationship between child and mother.

20 Smoking and ADHD was only correlated where the M & Ch were genetically related. THE REARING PARENTAL COMPARE INFLUENCES LIFESTLYE IVF BY THAT SMOKING SPERM CHILDREN V EGG DURING SHARE DONATION PREGNANCY WITHIN FAMILIES DON T CARDIFF CAUSE IVF STUDY ADHD G M CHILD Ch ADHD IVF through sperm donation E M & Ch genetically related IVF through egg donation M G CHILD Ch ADHD E M & Ch not genetically related

SHARE DONATION PREGNANCY WITHIN FAMILIES DON T CARDIFF CAUSE IVF STUDY ADHD G M CHILD Ch ADHD IVF

21 Smoking and ADHD was only correlated where the M & Ch were genetically related. THE REARING PARENTAL COMPARE INFLUENCES LIFESTLYE IVF BY THAT SMOKING SPERM CHILDREN V EGG DURING SHARE DONATION PREGNANCY WITHIN FAMILIES DON T CARDIFF CAUSE IVF STUDY ADHD G M CHILD Ch ADHD IVF through sperm donation E M & Ch genetically related IVF through egg donation M G CHILD Ch ADHD E M & Ch not genetically related

22 DO THESE CORRELATIONS EXTEND TO PARENTING? G P CHILD Ch ADHD E Lifford, Harold & Thapar, 2009 Correlation between Ch-ADHD & parenting largely due to G

23 WHAT MIGHT MEDIATE THESE PASSIVE G EFFECTS? G P PARENT ADHD CHILD Ch ADHD Moroney et al, 2017 E Parenting ADHD mediates P- adds & Ch-ADHD to the pathway special correlated from family P- to environment Ch-ADHD

24 EXPLAINING ADHD REARING E CORRELATIONS (AGAIN)

25 OPTION 2: EVOCATIVE GxE CORRELATION G P CHILD Ch ADHD E G create E via the impact of the child s ADHD behaviour

26 HOW CHILD ADHD IMPACTS ADOPTIVE PARENTS EARLY GROWTH & DEVELOPMENT STUDY Familial early child hyperactivity evokes adoptive parent hostility that increases ADHD. Genetically Related Genetically Unrelated.19* Adoptive Mother Hostility..42**+.12 * Child ADHD Birth Mother ADHD.15* Child hyperactivity 18 mths 4.5 yrs 4.5 years 6 years

HOW CHILD ADHD IMPACTS ADOPTIVE PARENTS EARLY GROWTH & DEVELOPMENT STUDY Familial but early child most hyperactivity especially childhood evokes adoptive conduct parent problems hostility that

27 HOW CHILD ADHD IMPACTS ADOPTIVE PARENTS EARLY GROWTH & DEVELOPMENT STUDY Familial but early child most hyperactivity especially childhood evokes adoptive conduct parent problems hostility that increases ADHD. Genetically Related Genetically Unrelated Birth Mother ADHD.15*.19* Child hyperactivity Adoptive Mother Hostility..42**+.12 *.30** Child ADHD.32**.22*+ Child Conduct 18 mths 4.5 yrs 4.5 years 6 years

28 EVOCATIVE GE OPTION MAY CREATE 2: EVOCATIVE COERCIVE GxE CYCLES CORRELATION BETWEEN PARENTS & THEIR ADHD CHILDREN If we can train parents to be less reactive to ADHD we can improve outcome for children.

29 ARE REARING EFFECTS MISSED GxE INTERACTIONS BECAUSE THEY ARE CONDITIONED BY G? G P CHILD Ch ADHD E G may activate Family E?

30 HOW ELSE MIGHT REARING E BE IMPORTANT? GxE INTERACTIONS CAUTION Results for GxE and ADHD very inconsistent and replication rare. Serotonin transporter interacts with conflict and cohesion.

ORMATIVE ERA STUDY REARING A E UNIQUE PROBABLY NATURAL PLAY EXPERIMENT A MARGINAL, ON COMPLEX EARLY ROLE SEVERE

PRE-1990 s RADICAL AND PRECISELY TIMED CHANGE ADOPTION SEVERELY RESTRICTED DIET - LITTLE SOCIAL OR COGNITIVE

TO 25 YEARS 165 children placed between Feb 1990 and Sept 1992. 52 UK adoptees.

31 ORMATIVE ERA STUDY REARING A E UNIQUE PROBABLY NATURAL PLAY EXPERIMENT A MARGINAL, ON COMPLEX EARLY ROLE SEVERE DEPRIVATION IN ADHD AETIOLOGY AND DEVELOPMENT ADOPTION OF PROFOUNDLY DEPRIVED INFANTS FROM ROMANIAN ORPHANAGES PRE-1990 s RADICAL AND PRECISELY TIMED CHANGE ADOPTION SEVERELY RESTRICTED DIET - LITTLE SOCIAL OR COGNITIVE STIMULATION 1 TO 43 MONTHS Deprivation duration likely un-confounded with genetic risk NURTURING, SUPPORTIVE FAMILY 22 TO 25 YEARS 165 children placed between Feb 1990 and Sept UK adoptees. Followed up at ages 4, 6, 11 and 15 and now in young adulthood. What Could about they induce extraordinarily extreme non-family brain plasticity adverse that environment? overrides G?

32 TWO EDGES OF THE NEUROPLASTICITY SWORD BRAIN REMARKABLE STUNTING AND CATCH RECOVERY UP INITIAL DEPRIVATION DEVASTATING FOLLOWED EFFECTS BY OF ADOPTION DEPRIVATION - BRAIN FOLLOWED GROWTH BY TWO EDGES OF THE NEUROPLASTICITY SWORD BRAIN STUNTING AND RECOVERY ARRIVE IN THE ADOPTIVE HOME DEVIATION FROM UK NORMS (sd) 1 TO 43 MONTHS 22 TO 25 YEARS YEARS FROM ADOPTION -5-6

33 REMISSION OF COGNITIVE IMPAIRMENT BUT PERSISTENCE OF NEURO-DEVELOPMENTAL PROBLEMS

34 PERSISTENCE OF DEPRIVATION-RELATED ADHD DIAGNOSIS

35 % CASES YOUNG ADULT PRESENTATION UK <6 > HYPER/IMPULSIVE INATTENTIVE COMBINED ANY PRESENTATION

36 % CASES ADOLESCENT AND ADULT RATES OF ADHD low risk (n=85) c 2 =17.46 high risk (n=60) c 2 = : : 7.7 AGE 15 YOUNG ADULT

37 CONCLUSIONS Within normative E, shared G rather shared rearing E largely determines ADHD. Links between ADHD and rearing E likely due to passive or evocative GE correlations. GxE interactions may also play a role. Reducing parents reactivity should improve outcomes (special provision for parents with ADHD). Extraordinary E such as extreme ID can override G to create severe ADHD risks? Paradoxically this highlights the potential of therapeutic extraordinary environments to shape underlying brain development.

38 PREVENTION NEUROSCIENCE WASS GAZE CONTINGENT ATTENTION TRAINING FOR INFANTS Principle Sophisticated reflection-based eye-tracking technology allows the direct training of attention through gaze contingent interaction even at this age.

39 TASK SUSTAINED ATTENTION

40 TASK INTERFERENCE CONTROL A B Trial 1 No conflict Trial 2 Conflict

41 INTERSTAARS CAN ATTENTION TRAINING IN INFANCY REDUCE ADHD RISK LONG TERM Birkbeck - Mark Johnson - Sam Wass INTERSTAARS IS STILL - Emily Jones RECRUITING - Simona Salomone - Patrick Bolton - Tim Smith - Luke Mason IF YOU HAVE A FAMILY - Tony MEMBER Charman - Andrew Pickles WITH ADHD AND AN INFACT - Emily Robinson WHO University WILL of Southampton BE OVER 6 MONTHS - Abigail OF Runicles AGE - Edmund THIS Sonuga-Barke YEAR PLEASE DROP ME A - Anna Hunt LINE - Martin Ruddock Our funders: MQ University of East London King s College London Transforming Mental Health and the Medical Research Council edmund.sonuga-barke@kcl.ac.uk.

Multiple Approaches to Studying Gene-Environment Interplay. Sara Jaffee University of Pennsylvania

Multiple Approaches to Studying Gene-Environment Interplay Sara Jaffee University of Pennsylvania What is GE Interplay? Gene-environment correlation (rge): Individual differences in exposure to environments