TOWARDS AN EARLY IDENTIFICATION AND INTERVENTION MODEL FOR ADHD

Transcription

1 TOWARDS AN EARLY IDENTIFICATION AND INTERVENTION MODEL FOR EDMUND SONUGA-BARKE D B B L Presented at 25 th Anniversary Conference association of Iceland Reykiavic, Oct Developmental Brain-Behaviour Unit School of Psychology

2 INSTITUTE FOR DISORDERS OF IMPULSE & ATTENTION (IDIA) UNIVERSITY OF SOUTHAMPTON

3 INSTITUTE FOR DISORDERS OF IMPULSE & ATTENTION (IDIA) UNIVERSITY OF SOUTHAMPTON

4 INSTITUTE FOR DISORDERS OF IMPULSE & ATTENTION (IDIA) UNIVERSITY OF SOUTHAMPTON

5 SOUTHAMPTON HOME OF THE..

6 SOUTHAMPTON HOME OF THE..

7 SOUTHAMPTON HOME OF THE..

8 SOUTHAMPTON HOME OF THE.. PROGRAMME FOR EARLY DETECTION & INTERVENTION FOR P1: Can we predict which hyperactive preschoolers will go onto have problems? PEDIA P2 & P3: What are barriers to effective early intervention? P4: Can we adapt parent training to address barriers? P5: Is adapted-nfpp better than the recommended parenting programme?

9 OUTLINE The need for early intervention in. Early intervention models prevention versus treatment. The developmental complexity of risk The value of early intervention for Integrating neuroscience into parenting approaches.

10 THE CASE FOR EARLY INTERVENTION IN

11 EARLY DETECTION AND INTERVENTION HAS A DUAL PURPOSE 1) TREAT EARLY APPEARING. 2) PREVENT THE LATER DEVELOPMENT & ESCALATION OF AND RELATED PROBLEMS.

12 EARLY DETECTION AND INTERVENTION HAS A DUAL PURPOSE 1) TREAT EARLY APPEARING. 2) PREVENT THE LATER DEVELOPMENT & ESCALATION OF AND RELATED PROBLEMS.

13 CAN ALREADY BE FULLY PRESENT IN PRESCHOOL The preschool diagnosis has validity. symptoms cluster/distinguished from other clusters associated with significant impairment at extremes specific neuro-psychological bases Dramatic increase diagnosis/stimulant use Historically poor provision/unmet needs Early intervention needed to reduce already present preschool burden.

14 THE PREDICTIVE VALIDITY OF THE PRESCHOOL DIAGNOSIS Lahey et al. (2009). Cohort of 4-6 year olds 96 pervasive impairment 29 situational impairment 130 non- DISC DSM-IV diagnosis (either/or) plus home and school functioning Followed up at yearly intervals

15 Results for follow up waves 2-4 These findings strongly support the predictive validity of the DSM-IV criteria for. Lahey et al. (2009)

16 CAN ALREADY BE FULLY PRESENT IN PRESCHOOL The preschool diagnosis has validity. symptoms cluster/distinguished from other clusters associated with significant impairment at extremes specific neuro-psychological bases Dramatic increase diagnosis/stimulant use Historically poor provision/unmet needs Early intervention needed to reduce already present preschool burden.

17 Number per 1000 PRESCRIBING TRENDS - PRESCHOOLERS (Zito: JAMA 2000) Recent report cites 49% increase in use of behavioral medications for in children under age 5

18 CAN ALREADY BE FULLY PRESENT IN PRESCHOOL The preschool diagnosis has validity. symptoms cluster/distinguished from other clusters associated with significant impairment at extremes specific neuro-psychological bases Dramatic increase diagnosis/stimulant use Historically poor provision/unmet needs Early intervention needed to reduce already present preschool burden.

19 EARLY DETECTION AND INTERVENTION HAS A DUAL PURPOSE 1) TREAT EARLY APPEARING. 2) PREVENT THE LATER DEVELOPMENT & ESCALATION OF AND RELATED PROBLEMS.

20 DEVELOPMENTAL CONTINUITIES AND ESCALATIONS Early Acting Risk Processes NASCENT Genetic, Environmental & Biological Markers

21 DEVELOPMENTAL CONTINUITIES AND ESCALATIONS Early Sub-clinical Signs in Preschool PRODROME High Activity, Speech/Motor Delay, Difficult Temperament Early Acting Risk Processes NASCENT Genetic, Environmental & Biological Markers

22 DEVELOPMENTAL CONTINUITIES AND ESCALATIONS Clinical Condition in Middle Childhood Early Sub-clinical Signs in Preschool FULL PRODROME Diagnostic Criteria Met High Activity, Speech/Motor Delay, Difficult Temperament Early Acting Risk Processes NASCENT Genetic, Environmental & Biological Markers

23 DEVELOPMENTAL CONTINUITIES AND ESCALATIONS Emergence of Comorbidity in Later Adolescence Clinical Condition in Middle Childhood Early Sub-clinical Signs in Preschool COMPLEX FULL PRODROME Conduct Disorder, Depression, Anxiety Diagnostic Criteria Met High Activity, Speech/Motor Delay, Difficult Temperament Early Acting Risk Processes NASCENT Genetic, Environmental & Biological Markers

24 Prevalence rate (%) IT S A COMPLEX DISORDER COMORBIDITY IS THE NORM CHILD ODD CD MD Anx LD Comorbidity Biederman, 2004

25 DEVELOPMENTAL CONTINUITIES AND ESCALATIONS Spirals of Dysfunction in Adulthood Emergence of Comorbidity in Later Adolescence Clinical Condition in Middle Childhood Early Sub-clinical Signs in Preschool ESCAL TING COMPLEX FULL PRODROME Personality Disorders, Substance Abuse Conduct Disorder, Depression, Anxiety Diagnostic Criteria Met High Activity, Speech/Motor Delay, Difficult Temperament Early Acting Risk Processes NASCENT Genetic, Environmental & Biological Markers

26 Prevalence rate (%) Prevalence rate (%) IT S A COMPLEX DISORDER COMORBIDITY IS THE NORM CHILD ADULT ODD CD MD Anx LD 0 ASD MD Anx Alc Comorbidity Comorbidity Biederman, 2004

27 Prevalence rate (%) Prevalence rate (%) IT S A COMPLEX DISORDER COMORBIDITY IS THE NORM CHILD ADULT ODD CD MD Anx LD 0 ASD MD Anx Alc Comorbidity Comorbidity Biederman, 2004

28 THE INCREMENTAL DEVELOPMENTAL BURDEN OF ESCAL TING COMPLEX FULL PRODROME NASCENT

29 IMPAIRMENT ESCAL TING COMPLEX FULL PRODROME NASCENT

30 IMPAIRMENT ESCAL TING COMPLEX FULL PRODROME NASCENT

31 IMPAIRMENT ESCAL TING COMPLEX FULL PRODROME NASCENT

32 IMPAIRMENT ESCAL TING COMPLEX FULL PRODROME NASCENT

33 IMPAIRMENT ESCAL TING COMPLEX FULL PRODROME NASCENT

34 IMPAIRMENT ESCAL TING COMPLEX FULL PRODROME NASCENT

35

36 IMPACT ON FAMILY & COMMUNITY IMPAIRMENT ESCAL TING COMPLEX FULL PRODROME NASCENT

37 ECONOMIC BURDEN HEALTH, EDUCATION & JUSTICE IMPACT ON FAMILY & COMMUNITY IMPAIRMENT ESCAL TING COMPLEX FULL PRODROME NASCENT

38 IS A MAJOR HEALTH BURDEN It is evident, from the above review, that is associated with a significant financial and emotional costs to the healthcare system, education services, carers and families and society as a whole. NICE, (2009) Overall national annual incremental costs of ranged from $143 to $266 billion (B). Most of these costs were incurred by adults ($105B $194B) compared with children/adolescents ($38B $72B). For adults, the largest cost category was productivity and income losses ($87B $138B). Doshi et al., (2012)

39 ESCALATION OF MEIDCATION USE UK SITUATION Quality Care Commission, 2013

40 Dalsgaard, Nielsen Simonsen, 2013 ESCALATION OF MEIDCATION USE DANISH SITUATION

41 AS WELL AS TREATING PRESCHOOL EARLY INTERVENTION STRATEGIES COULD BE USEFUL IN.. PREVENTING - EMERGENCE OF FROM NASCENT AND PRODROMAL FORMS LIMIT - ESCALATION TO MORE COMPLEX /SEVERE FORMS. REDUCE ITS IMPACT ON THE CHILD, THEIR FAMILY AND SOCIETY...REDUCING THE NEED FOR THE LONF TERM USE MEDICATION.

42 WHY SHOULD EARLY INTERVENTION WORK BETTER? Evidence for efficacy of later non-pharma interventions limited. Early intervention is expected to be more effective because Its exploits plasticity Child s brain more open to environmental influence? Child s behavioural habits less engrained? It is in a clinical window of opportunity Parent less set and rigid more open to change? Less comorbidity easier access to core problems.

43 EARLY INTERVENTION MODELS LEVELS OF PREVENTION

44 LEVEL PREVENTION TARGET LEVELS OF PREVENTION PRIMORDIAL OPTIMISE ENVIRONMENT REDUCE RISK EXPOSURE PRE-NATAL

45 LEVEL PREVENTION TARGET LEVELS OF PREVENTION PRIMORDIAL OPTIMISE ENVIRONMENT REDUCE RISK EXPOSURE PRIMARY TARGET EARLY SIGNS IN PRODROME TO LIMIT ONSET PRE-NATAL INFANCY

46 LEVEL PREVENTION TARGET LEVELS OF PREVENTION PRIMORDIAL PRIMARY SECONDARY OPTIMISE ENVIRONMENT REDUCE RISK EXPOSURE TARGET EARLY SIGNS IN PRODROME TO LIMIT ONSET EARLY TARGETING OF FULL CASES TO LIMIT CONTINUITIES PRE-NATAL INFANCY EARLY CHILDHOOD

47 LEVEL PREVENTION TARGET LEVELS OF PREVENTION PRIMORDIAL PRIMARY SECONDARY TERTIARY OPTIMISE ENVIRONMENT REDUCE RISK EXPOSURE TARGET EARLY SIGNS IN PRODROME TO LIMIT ONSET EARLY TARGETING OF FULL CASES TO LIMIT CONTINUITIES LATE TARGETING TO LIMIT ESCALATION & BURDEN PRE-NATAL INFANCY EARLY CHILDHOOD LATE CHILDHOOD ADOLESCENCE

48 ECONOMIC BURDEN HEALTH, EDUCATION & JUSTICE IMPACT ON FAMILY & COMMUNITY IMPAIRMENT ESCAL TING COMPLEX FULL PRODROME NASCENT

49 ECONOMIC BURDEN HEALTH, EDUCATION & JUSTICE IMPACT ON FAMILY & COMMUNITY IMPAIRMENT ESCAL TING COMPLEX FULL PRODROME NASCENT

50 ECONOMIC BURDEN HEALTH, EDUCATION & JUSTICE IMPACT ON FAMILY & COMMUNITY IMPAIRMENT COMPLEX FULL PRODROME NASCENT

51 ECONOMIC BURDEN HEALTH, EDUCATION & JUSTICE IMPACT ON FAMILY & COMMUNITY IMPAIRMENT COMPLEX FULL PRODROME NASCENT

52 ECONOMIC BURDEN HEALTH, EDUCATION & JUSTICE IMPACT ON FAMILY & COMMUNITY IMPAIRMENT FULL PRODROME NASCENT

53 ECONOMIC BURDEN HEALTH, EDUCATION & JUSTICE IMPACT ON FAMILY & COMMUNITY IMPAIRMENT FULL PRODROME NASCENT

54 ECONOMIC BURDEN HEALTH, EDUCATION & JUSTICE IMPACT ON FAMILY & COMMUNITY IMPAIRMENT PRODROME NASCENT

55 ECONOMIC BURDEN HEALTH, EDUCATION & JUSTICE IMPACT ON FAMILY & COMMUNITY IMPAIRMENT PRODROME NASCENT

56 ECONOMIC BURDEN HEALTH, EDUCATION & JUSTICE IMPACT ON FAMILY & COMMUNITY IMPAIRMENT NASCENT

57 LEVEL PREVENTION TARGET LEVELS OF PREVENTION PRIMORDIAL PRIMARY SECONDARY TERTIARY OPTIMISE ENVIRONMENT REDUCE RISK EXPOSURE TARGET EARLY SIGNS IN PRODROME TO LIMIT ONSET EARLY TARGETING OF FULL CASES TO LIMIT CONTINUITIES LATE TARGETING TO LIMIT ESCALATION & BURDEN PRE-NATAL INFANCY EARLY CHILDHOOD LATE CHILDHOOD ADOLESCENCE

58 LEVEL PREVENTION TARGET LEVELS OF PREVENTION PRIMORDIAL PRIMARY SECONDARY TERTIARY OPTIMISE ENVIRONMENT REDUCE RISK EXPOSURE TARGET EARLY SIGNS IN PRODROME TO LIMIT ONSET EARLY TARGETING OF FULL CASES TO LIMIT CONTINUITIES LATE TARGETING TO LIMIT ESCALATION & BURDEN PRE-NATAL INFANCY EARLY CHILDHOOD LATE CHILDHOOD ADOLESCENCE POPULATION WIDE PUBLIC EDUCATION

59 LEVEL PREVENTION TARGET LEVELS OF PREVENTION PRIMORDIAL PRIMARY SECONDARY TERTIARY OPTIMISE ENVIRONMENT REDUCE RISK EXPOSURE TARGET EARLY SIGNS IN PRODROME TO LIMIT ONSET EARLY TARGETING OF FULL CASES TO LIMIT CONTINUITIES LATE TARGETING TO LIMIT ESCALATION & BURDEN PRE-NATAL INFANCY EARLY CHILDHOOD LATE CHILDHOOD ADOLESCENCE POPULATION WIDE COMMUNITY SCREEN PUBLIC EDUCATION GENTLE BROADLY TARGETED INTERVENTION

60 LEVEL PREVENTION TARGET LEVELS OF PREVENTION PRIMORDIAL PRIMARY SECONDARY TERTIARY OPTIMISE ENVIRONMENT REDUCE RISK EXPOSURE TARGET EARLY SIGNS IN PRODROME TO LIMIT ONSET EARLY TARGETING OF FULL CASES TO LIMIT CONTINUITIES LATE TARGETING TO LIMIT ESCALATION & BURDEN PRE-NATAL INFANCY EARLY CHILDHOOD LATE CHILDHOOD ADOLESCENCE POPULATION WIDE COMMUNITY SCREEN CLINICAL ASSESSMENT PUBLIC EDUCATION GENTLE BROADLY TARGETED INTERVENTION AGGRESSIVE INT RVENTION FOR CASES AT RISK FOR PERSISTENCE

61 LEVEL PREVENTION TARGET LEVELS OF PREVENTION PRIMORDIAL PRIMARY SECONDARY TERTIARY OPTIMISE ENVIRONMENT REDUCE RISK EXPOSURE TARGET EARLY SIGNS IN PRODROME TO LIMIT ONSET EARLY TARGETING OF FULL CASES TO LIMIT CONTINUITIES LATE TARGETING TO LIMIT ESCALATION & BURDEN PRE-NATAL INFANCY EARLY CHILDHOOD LATE CHILDHOOD ADOLESCENCE POPULATION WIDE COMMUNITY SCREEN CLINICAL ASSESSMENT CLINICAL ASSESSMENT PUBLIC EDUCATION GENTLE BROADLY TARGETED INTERVENTION AGGRESSIVE INT RVENTION FOR CASES AT RISK FOR PERSISTENCE AGGRESSIVE INT RVENTION FOR CASES AT RISK FOR BURDEN

62 THE PREVENTATIVE EFFICACY OF EARLY INTERVENTION DEPENDS ENTIRELY ON THE ABILITY TO BOTH CHARACTERISE RISK PATHWAYS AND IDENTIFY THOSE INDIVIDUALS AT RISK. AS WE KNOW MORE ABOUT HOW COMPLEX THESE PROCESSES ARE THE LESS CONFIDENT WE HAVE BECOME IN OUR ABILITY TO MAKE INDIVIDUAL RISK ASSESSMENTS

63 THE DEVELOPMENTAL COMPLEXITY OF RISK

64 BUT SURELY ITS SIMPLE ITS ALL IN THE GENES! WE WILL BE ABLE TO PREDICT EVEN BEFORE BIRTH WHEN WE CAN DIRECTLY MEASURE GENETIC RISK G

65 BUT SURELY ITS SIMPLE ITS ALL IN THE GENES! DESPITE MAJOR ADVANCES WE ARE LONG WAY SHORT OF UNDERSTANDING GENETIC RISK FOR?

66 BUT SURELY ITS SIMPLE ITS ALL IN THE GENES! DESPITE MAJOR ADVANCES WE ARE LONG WAY SHORT OF UNDERSTANDING GENETIC RISK FOR?

67 WHAT IS INCREASINGLY CLEAR IS THAT MULTIPLE GENES OF SMALL EFFECT WORK TOGETHER TO INCREASE LIABILITY EASY THEN - JUST ADD EFFECTS TOGETHER TO ESTIMATE RISK G 1 G 2 G 3 G 4 G 5 G 6 Neale et al., 2010

68 WHAT IS INCREASINGLY CLEAR IS THAT MULTIPLE GENES OF SMALL EFFECT WORK TOGETHER TO INCREASE LIABILITY EASY THEN - JUST ADD EFFECTS TOGETHER TO ESTIMATE RISK G 1 G 2 G 3 G 4 G 5 G 6 G 1 G 2 G 3 G 4 G 5 G 6 Neale et al., 2010

69 WHAT IS INCREASINGLY CLEAR IS THAT MULTIPLE GENES OF SMALL EFFECT WORK TOGETHER TO INCREASE LIABILITY EASY THEN - JUST ADD EFFECTS TOGETHER TO ESTIMATE RISK G 1 G 2 G 3 G 4 G 5 G 6 G 1 G 2 G 3 G 4 G 5 G 6 G 1 G 2 G 3 G 4 G 5 G 6 Neale et al., 2010

70 WHAT IS INCREASINGLY CLEAR IS THAT MULTIPLE GENES OF SMALL EFFECT WORK TOGETHER TO INCREASE LIABILITY EASY THEN - JUST ADD EFFECTS TOGETHER TO ESTIMATE RISK G 1 G 2 G 3 G 4 G 5 G 6 G 1 G 2 G 3 G 4 G 5 G 6 G 1 G 2 G 3 G 4 G 5 G 6 Stergiakouli et al, 2012

71 PRENATAL ENVIRONMENTS ARE IMPORTANT TOO AGAIN MULTIPLE ENVIRONMENTAL RISKS OF SMALL EFFECT G 1 G 2 G 3 G 4 G 5 G 6 Banerjee et al, 2007

72 BUT EVEN IF THIS WERE POSSIBLE YOU NEED TO MEASURE THE MULTIPLE PRENATAL ENVIRONMENTAL RISKS OK JUST ADD THEM TOGETHER WITH THE GENES G 1 G 2 G 3 G 4 G 5 G 6 E 1 E 2 E 3 E 4 E 5 E 6

73 BUT THAT WONT WORK - GENES AND ENVIRONMENTS ACT TOGETHER IN COMPLEX WAYS TO DETERMINE RISK FIRST, GENES CAN DETERMINE ENVIRONMENTAL EXPOSURES G 1 G 2 G 3 G 4 G 5 G 6 E 1 E 2 E 3 E 4 E 5 E 6 Thaper et al., 2009

74 GENES CAN MODERATE THE EFFECTS OF ENVIRONMENTAL RISK GENE X ENVIRONMENT INTERACTIONS G 1 G 2 G 3 G 4 G 5 G 6 E 1 E 2 E 3 E 4 E 5 E 6

75 GENES CAN MODERATE THE EFFECTS OF ENVIRONMENTAL RISK GENE X ENVIRONMENT INTERACTIONS G 1 G 2 G 3 G 4 G 5 G 6 DOPAMINE TRANSPORTER GENE E 1 E 2 E 3 E 4 E 5 E 6 Neuman et al, 2006

76 ENVIRONMENTS CAN ALTER THE EXPRESSION OF GENES EPIGENETICS G 1 G 2 G 3 G 4 G 5 G 6 E 1 E 2 E 3 E 4 E 5 E 6

77 ENVIRONMENTS CAN ALTER THE EXPRESSION OF GENES EPIGENETICS G 1 G 2 G 3 G 4 G 5 G 6 E 1 E 2 E 3 E 4 E 5 E 6 STRESS GLUCO- CORTICOID RECEPTOR GENE? Mill et al, 2008

78 IT MAY BE BETTER TO THINK OF GENES AND ENVIRONMENTS ACTING TOGETHER TO CREATE A SPECTRUM BIOLOGICAL LIABILITY FOR G 1 G 2 HI G 3 G 4 G 5 G 6 LIABILITY E 1 E 2 E 3 E 4 E 5 E 6 LO

79 IT MAY BE BETTER TO THINK OF GENES AND ENVIRONMENTS ACTING TOGETHER TO CREATE A SPECTRUM BIOLOGICAL LIABILITY FOR G 1 G 2 G 3 G 4 G 5 G 6 HI LIABILITY E 1 E 2 E 3 E 4 E 5 E 6 LO

80 GENES AND PRENATAL ENVIRONMENTS ACT TOGETHER TO CREATE A SPECTRUM BIOLOGICAL LIABILITY FOR G 1 G 2 HI G 3 G 4 G 5 G 6 LIABILITY E 1 E 2 E 3 E 4 E 5 E 6 LO

81 IT MAY BE BETTER TO THINK OF GENES AND ENVIRONMENTS ACTING TOGETHER TO CREATE A SPECTRUM BIOLOGICAL LIABILITY FOR G 1 G 2 HI G 3 G 4 G 5 G 6 LIABILITY E 1 E 2 E 3 E 4 E 5 E 6 LO

82 IT MAY BE BETTER TO THINK OF GENES AND ENVIRONMENTS ACTING TOGETHER TO CREATE A SPECTRUM BIOLOGICAL LIABILITY FOR G 1 G 2 HI G 3 G 4 G 5 G 6 E 1 E 2 E 3 E 4 E 5 E 6 LIABILITY LO

83 IT MAY BE BETTER TO THINK OF GENES AND ENVIRONMENTS ACTING TOGETHER TO CREATE A SPECTRUM BIOLOGICAL LIABILITY FOR G 1 G 2 HI G 3 G 4 G 5 G 6 LIABILITY E 1 E 2 E 3 E 4 E 5 E 6 LO

84 I GET THE MESSAGE BUT SURELY WE CAN PREDICT WHICH INFANTS/PRESCHOOLERS WILL DEVELOP SOON AFTER BIRTH. THINGS ARE PRETTY MUCH SET FROM THERE ON RIGHT? G 1 G 2 HI G 3 G 4 G 5 G 6 LIABILITY E 1 E 2 E 3 E 4 E 5 E 6 LO Sonuga-Barke et al, 2005 DEVELOPMENTAL TIME

85 I GET THE MESSAGE BUT SURELY WE CAN PREDICT WHICH INFANTS/PRESCHOOLERS WILL DEVELOP SOON AFTER BIRTH. THINGS ARE PRETTY MUCH SET FROM THERE ON RIGHT? G 1 G 2 HI G 3 G 4 G 5 G 6 LIABILITY E 1 E 2 E 3 E 4 E 5 E 6 LO Sonuga-Barke et al, 2005 DEVELOPMENTAL TIME

86 I GET THE MESSAGE BUT SURELY WE CAN PREDICT WHICH INFANTS/PRESCHOOLERS WILL DEVELOP SOON AFTER BIRTH. THINGS ARE PRETTY MUCH SET FROM THERE ON RIGHT? G 1 G 2 G 3 G 4 G 5 G 6 HI LIABILITY E 1 E 2 E 3 E 4 E 5 E 6 LO Sonuga-Barke et al, 2005 DEVELOPMENTAL TIME

87 EARLY HYPERACTIVITY/DIFFICULT TEMPERAMENT INCREASE RISK BUT DISCONTINUITUES EXIST THERE ARE MULTIPLE DEVELOPMENTAL PHENOTYPES G 1 G 2 HI G 3 G 4 G 5 G 6 LIABILITY E 1 E 2 E 3 E 4 E 5 E 6 LO Sonuga-Barke et al, 2005 DEVELOPMENTAL TIME

88 EARLY ONSET PERSISTING G 1 G 2 HI G 3 G 4 G 5 G 6 LIABILITY E 1 E 2 E 3 E 4 E 5 E 6 LO Sonuga-Barke et al, 2005 DEVELOPMENTAL TIME

89 EARLY ONSET - DESISTING G 1 G 2 G 3 G 4 HI G 5 G 6 LIABILITY E 1 E 2 E 3 E 4 E 5 E 6 LO Sonuga-Barke et al, 2005 DEVELOPMENTAL TIME

90 LATE ONSET G 1 G 2 HI G 3 G 4 G 5 G 6 LIABILITY E 1 E 2 E 3 E 4 E 5 E 6 LO Sonuga-Barke et al, 2005

91 EARLY ONSET ESCALATING/COMPLEX G 1 G 2 G 3 G 4 G 5 G 6 HI +ODD + CD + PD & MD LIABILITY E 1 E 2 E 3 E 4 E 5 E 6 LO Sonuga-Barke et al, 2005 DEVELOPMENTAL TIME

92 TO BE ABLE TO IDENTIFY WHICH INFANTS ARE AT RISK FOR WE NEED TO BE ABLE TO MAP DEVELOPMENT PHENOTYPES ON TO GENETIC AND ENVIRONMENTAL RISK PROCESSES. THE INTERPLAY BETWEEN GENES AND ENVIRONMENTS IS LIKELY TO BE AS COMPLICATED AS IN PRE-NATAL PERIOD.

93 THE DEVELOPMENT OF COMORBID COULD INVOLVE THE COMPLEX INTERPLAY BETWEEN GENETIC AND ENVIR EFFECTS G 1 G 2 G 3 G 4 G 5 G 6 HI +ODD + CD + PD & MD LIABILITY E 1 E 2 E 3 E 4 E 5 E 6 LO

94 PARENT EFFECTS G 1 G 2 G 3 G 4 G 5 G 6 HI +ODD + CD + PD & MD E 1 E 2 E 3 E 4 E 5 E 6 LIABILITY LO ABUSE & HOSTILITY Taylor et al, 2001

95 CHILD EFFECTS INCLUDING EVOCATIVE GE G 1 G 2 G 3 G 4 G 5 G 6 HI +ODD + CD + PD & MD E 1 E 2 E 3 E 4 E 5 E 6 LIABILITY LO ABUSE & HOSTILITY Cartwright et al., 2011

96 GENETIC MAIN EFFECTS LATE ACTING GENES CD RISK MOOD RISK G 1 G 2 G 3 G 4 G 5 G 6 HI +ODD + CD + PD & MD LIABILITY E 1 E 2 ABUSE & HOSTILITY E 3 E 4 E 5 E 6 LO Thapar et al, 2001

97 PASSIVE GENE ENVIRONMENT CORRELATIONS LATE ACTING GENES G 1 G 2 G 3 G 4 G 5 G 6 HI +ODD + CD + PD & MD E 1 E 2 LIABILITY ABUSE & HOSTILITY E 3 E 4 E 5 E 6 LO PASSIVE GE Jaffee et al, 2008

98 GENETIC MODERATORS OF PARENT EFFECTS LATE ACTING GENES G 1 G 2 G 3 G 4 G 5 G 6 HI MODERATOS +ODD + CD + PD & MD E 1 E 2 E 3 E 4 E 5 E 6 LIABILITY LO ABUSE & HOSTILITY Sonuga-Barke et al, 2009

99 THE DEVELOPMENT OF COMORBID COULD INVOLVE THE COMPLEX INTERPLAY BETWEEN GENETIC AND ENVIR EFFECTS G 1 G 2 G 3 G 4 G 5 G 6 E 1 E 2 E 3 E 4 E 5 E 6 LATE ACTING GENES HI LIABILITY LO MODERATOS CD RISK +ODD MOOD RISK + CD + PD & MD ABUSE & HOSTILITY

100 INITIAL REFLECTIONS PRIMORDIAL PRIMARY TARGET - NO AT RISK MARKERS OF PRACTICAL VALUE. INTERVENING - PUBLIC HEALTH TARGETS POSSIBLE (E.G.PREGANCY SMOKING). PRIMARY-SECONDARY TARGET - EARLY HYPERACTIVITY GENERALLY INTERVENE - DO PARENTING INTERVENTIONS REDUCE CONTINUITY? SECONDARY-TERTIARY TARGET - THOSE AT SOCIAL/FAMILIAL RISK INTERVENE CAN MEDICATION OR PSYCHO-SOCIAL REDUCE LONG TERM RISK OF COMPLICATIONS AND ESCALATION. AN URGENT NEED FOR LONGITUDINAL STUDIES OF RISK OF TRANSITIONS ACROSS RISK STAGES.

101 PREDICTIVE POWER OF THE PRODROME

102 PREDICTIVE POWER OF THE PRODROME

103 THE VALUE OF EARLY INTERVENTION

104 THE VALUE OF EARLY INTERVENTION MEDICATION

105 PRESCHOOL TREATMENT STUDY (PATS) Greenhill, et al., (2004). Aim to determine MPH safety & efficacy in preschoolers with using optimal dosing National Institute of Mental Health, June 3, 2002

106 PATS CONCLUSIONS MPH effect sizes were small to moderate (Cohen, 1988). Best MPH dose from PATS titration trial much lower than used in MTA. 8.7% of patients discontinued because of AEs related to MPH, main side effect differed from school aged children (emotional outbursts). Trial troubled by length, complexity, slow recruitment, attrition Growth data over a year shows 10 percentile drop in expected height while on MPH long term follow up studies needed Vitiello B, et al. (2007) J Child Adolesc Psychopharm, 17:

107 THE VALUE OF EARLY INTERVENTION PSYCHOLOGICAL

108

109 INCLUSION CRITERIA RCT (including non-blinded and cross over trials) Peer reviewed diagnosis (or meeting validated cut-off). 3 to 18 years Comorbidity Common comorbidities OK but not rarer comorbidities specifically selected for study (e.g. groups selected to have both and Autism). outcome. Suitable control (placebo/attention-active/wait list/tau). Meds can be included in TAU except where non-pharma is planned as an add on to meds.

110 RECORDS SCREENED/TRIALS INCLUDED

111 PSYCHOLOGICAL INTERVENTIONS BEHAVIOURAL INTERVENTIONS Rationale: behaviours can be modified by contingencies. Intervention: Psycho-education plus learning-based approaches to increase desired /reduce undesired behaviour (eg via parent/teacher). Meta analysis (e.g., Fabiano et al 2009) not only RCTs, outcomes/cases. COGNITIVE TRAINING Table 1: Typical sequence of elements in a standard parenting approach Rationale: Structured 1. Psychoeducation experience about alters and treatment brain structure/function. rationale Intervention: 2. Computerized Establish systematic adaptive reporting procedures - strengthen deficient circuits. 3. Attending to appropriate behaviors to modify Systematic 4. Giving review effective (Markomichali commands et al 2009) but no meta-analysis. 5. Establishing rules NEUROFEEDBACK 6. Time out/punishment 7. Home rewards and response cost Rationale: Individuals 8. Contingencies can outside learn the to home alter brain activity. Intervention: 9. Reward-based Problem solving techniques using brain visualisation to improve attention via 10. corticol Maintenance self-regulation. of therapy after weekly contact Meta-analysis (Arns et al 2009) but not only RCTs.

112 BEHAVIOURAL INTERVENTIONS M-PROX ES = 0.40*

113 BEHAVIOURAL INTERVENTIONS M-PROX ES = 0.40* P-BLIND ES = 0.02

114 CHILD OUTCOMES SUMMARY (SMD) 1 0,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 0,1 0 * * * * * N=17 N=13 N=7 N=7 CP SS ACAD MPROX PBLIND PBLIND (LOW MEDS)

115 CHILD OUTCOMES SUMMARY (SMD) 1 0,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 0,1 0 * * * * * N=17 N=7 N=13 N=7 N=7 N=7 CP SS ACAD MPROX PBLIND PBLIND (LOW MEDS)

116 CHILD OUTCOMES SUMMARY (SMD) 1 0,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 0,1 0 * * * * * N=17 N=7 N=5 N=13 N=7 N=5 N=7 N=4 N=7 CP SS ACAD MPROX PBLIND PBLIND (LOW MEDS)

117 ADULT OUTCOMES SUMMARY (SMD) 1,5 1,3 1,1 0,9 * * 0,7 0,5 0,3 0,1 * * * * * * -0,1 N=8 N=5 N=7 N=3 N=7 N=5 N=4 N=11 N=7 N=5 MH SELF POSITIVE NEGATIVE MPROX PBLIND PBLIND (LOW MEDS)

118 SYMPTOMS MPROX SYMPTOMS PBLIND

119 CP SYMPTOMS MPROX CP SYMPTOMS PBLIND

120 SUMMARY FOR BEHAVIOURAL INTERVENTIONS Behavioural interventions for have robust positive effects on parenting/parenting self concept. Effects on limited to un-blinded measures - due to parent expectations and/or changes in perceptions? Early intervention improved effects - still not significant. Some effects on CP especially in preschoolers. More blinded evidence needed before supportable as treatment/preventative strategy for early. Perhaps a completely different approach is needed.

121 Translational approaches hold out the promise that therapeutic innovation can be built on scientific discoveries about pathogenesis.

122 CAN WE OPTIMISE OUTCOMES BY INTEGRATING COGNITIVE APPROACHES INTO EARLY INTERVENTIONS?

123 CAN WM CAPACITY BE INCREASED (AND NOT JUST STRATEGIES IMPROVED) BY COMPUTERISED TRAINING? THE PIONEERING WORK BY KLINGBERG AND HISTEAM AT THE KAROLINSKA

124 TRAINING CHANGES BRAIN FUNCTION? Olesen PJ, et al. Nature Neurosci (1):75-9 Plasticity in neural systems underlying WM Right middle frontal gyrus Right inferior parietal cortex Intraparietal cortex

125 AJP REVIEW OF NON-PHARMA TREATMENTS Sonuga-Barke et al. Am J Psychiatry. 2013; AiA:1 15

126 AJP REVIEW OF NON-PHARMA TREATMENTS COGNITIVE TRAINING trials all with P-BLIND (N=207): Ages 6-13 years Treatments 2 WM training; 3 attention training Control 2 WLC; 3 control task 60% rated fair quality or above Sonuga-Barke et al. Am J Psychiatry. 2013; AiA:1 15

127 COGNITIVE TRAINING d. Cognitive Training Standardised Mean Difference (SMD) IV, Random, 95%CI Rabiner 2010 Shalev 2007 Klingberg 2005 Steiner 2011 Johnstone 2010 Johnstone 2012 M-PROX Overall Favours control Favours treatment Overall SMD (95% CI) = 0.64 (0.33,0.95) Test for overall effect: Z = 4.07, p = Heterogeneity: 2 = 6.91, df = 5, p= 0.23, I 2 = 28% ES = 0.64* P-BLIND ES = 0.24

128 CAN WE INCREASE DELAY TOLERANCE IN PRESCHOOLERS WHO CAN T WAIT? THE WAITING GAME TRAINING PROGRAMME PAVLINA MARKOMICHALI unpublished at present

129 A DUAL-COMPONENT TRAINING MODEL (SONUGA -BARKE, 2004) Two intervention targets IMPULSIVE DRIVE FOR IMMEDIATE REWARDS Weak Response-Delayed Reward association DELAY AVERSION Negative affect associated with delay How? Practice on responsedelayed reward situations to strengthen contingency. How? Densensitization - Repeated instances of achievable, rewarded delay (creating positive delay-related experiences)

130 CRITERIA DRIVEN INCREASE IN DELAY SESSION AVERAGE PROGRAMMED DELAY 17.5s 20s 22.5s 22.5s 25s DELAY TOLERATED PER SESSION MET CRITERIA GO TO LEVEL II MET CRITERIA GO TO LEVEL III NOT MET CRITERIA REPEAT LEVEL III MET CRITERIA GO LEVEL IV NOT MET CRITERIA REPEAT LEVEL IV s 27.5s MET CRITERIA GO TO LEVEL V

131 THE WAITING GAME PROCEDURE A B C you throw the dice to find out which sticker you won but wait until I say now BEFORE you can get the stickers Time D A B C A B C

132 WAITING GAME RCT Randomise to WG or WLC Children with delay-related difficulties (bottom 20% of class) Training efficiency measures: Mean Delay Time per trial Reward-oriented behaviour (Observational Checklist) Generalizability measures: Teachers ratings: SDQ, BRIEF-P, QDQ Computerised Battery of Delay Tasks

133 TRAINING EFFICIENCY

134 DEVELOPMENT OF DELAY TOLERANCE DURING TRIAL

135 PRESCHOOL TRAINING MAY BE OPTIMISED IF IMPLEMENTED AS PART OF EVERYDAY ROUTINES THE SOCIAL BASIS OF PSYCHOLOGICAL DEVELOPMENT AND EARLY INTERVENTION Normal interactions between parents and young children represent a..crucial forum for the internalisation of cognition and development of self regulation.and a potential therapeutic opening for the implementation and integration of cognitive training into the everyday lives of children at risk of. Vygotsky, Luria, Baumrind, Cole

136 CAN WE OPTIMISE OUTCOMES BY INTEGRATING COGNITIVE APPROACHES INTO EARLY INTERVENTIONS? ARE PARENT TRAINING PROGRAMMES SPECIALISED FOR BY INCOPORATING COGNITIVE TRAINING ELEMENTS BETTER THAN GENERIC ONES? Prototype Early Intervention Incorporating Cognitive Training Attention, Inhibition & Memory Training For Preschoolers With AIM - Tamm et al (2010). Training Executive, Affective & Memory Skills- TEAMS Halperin & Healey et al (2010). Revised New Forest Parenting Package NFPP Thompson, et al (2001; 2009).

137 DISTINCTIVE CORE GOAL - NFPP GENERAL GOALS TREATMENT TARGETS PSYCHOEDUCATIO N PARENT-CHILD PLAY MAJOR REVIEW PARENT-CHILD TASK FINAL REVIEW Week 1 Parent only Week 2 Parent only Week 3 Parent & Child Week 4 Parent & Child Week 5 Parent only Week 6 Parent & Child Week 7 Parent & Child Week 8 Parent only IMPROVE PARENTAL STYLE HELP PARENTS COMMUNICATE IMPROVE MANAGE OF ODD IMPROVE REGULATION THROUGH INTERACTION understanding parenting and constructive parent positive parent selforganisation listening skills authoritative talk clarity and consistency behavioural principles preventative strategies reward and sanctions consistency joint play and interaction reciprocity turn taking scaffolding

138 DISTINCTIVE CORE GOAL increase constructive parenting and the effectiveness of parents as facilitators of their child's development - enhance home as a context for learning selfcontrol/behavioral regulation. teach parents to change their child's experience (training/practice), to address areas of neuropsychological weakness (self regulation, delay tolerance and organisational skills).

139 CONSTRUCTIVE PARENTING Work within the children zone of proximal development to gradually increase their child self organisational skills, delay tolerance and working memory during episodes of everyday reciprocal interaction and mother-child play using (a) organised games and (b) identifying teachable moments by (a) scoping current levels of ability, identifying appropriate and realistic developmental goals, (b) providing the necessary support and encouragement to achieve those goals (i.e. scaffolding) and (c) consolidating through practice those developmental gains and (d) rescoping.

140 WLC v NFPP (SONUGA-BARKE ET AL., 2001) NFPP v TAU (THOMPSON ET AL., 2009) WLC AD/HD WLC CP SC AD/HD SC CP T1 T2 T3

141 SUMMARY The risk pathways to and from to other problems are extremely complex. Prodromal is the most promising primary prevention target. There is little evidence that early behavioural interventions can either treat early and none that it can arrest the developmental process. Translational approaches offer a new science driven perspective on therapeutic innovation. Integrating cognitive and motivational training into parent training - delivered during every-day routines - may represent a way to optimise prevention power.