55thth November 2010November 2010

Centre for Research in Autism & Education

Autism Research Centre

A research perspective on A research perspective on

(some of) the many (some of) the many

components of ASDcomponents of ASD

Dr Greg PascoCentre for Research in Autism & Education (CRAE)

Institute of Education

Topics

1. Personal perspective

2. Screening

3. Early profiles & ‘High Risk’ studies

4. Intervention

1. Personal perspective

Sources of research output

International Meeting for Autism Research (IMFAR)

A growing number of autism specific journals:

Journal of Autism & Developmental Disorders (JADD)

Autism

Autism Research

Research in Autism Spectrum Disorders

Focus on Autism and Other Developmental Disabilities

Molecular Autism

Sources of research funding

MRC

Wellcome Trust

Autism Speaks

Autistica

NIH (US)

NIHR (UK) (?)

Is there an imbalance towards “Causes and Cures” as opposed to evaluating good practice in everyday

clinical provision – early identification, diagnosis and treatment?

Fred Volkmar

2010 Emanuel Miller lecture at ACAMH:

Mike Rutter

Presentation at Autism Europe conference, Oct 2010

Genetics:Some associations with rare mutations but lack of specificity for ASD and

doubts re. explanatory cause

CNVs (esp deletions) 5-10% of ASD cases. Causal? Most CNVs arise de novo and therefore not familial and occur in non-ASD individuals

Genome-wide association studies (GWAS). Need huge samples, leading to false positives. “So far, so unimpressive” (Fombonne)

Why doesn’t autism become extinct?

Why haven’t susceptibility genes been identified?

H2 = 90%. Similar for other multifactorial conditions. Genetic heterogeneity with small effects for individual genes

Screening for autism in toddlersScreening for autism in toddlers

Is it possible?

Is it effective?

Is it desirable?

Autism Spectrum Condition (ASC) difficult to detect in very young children

Diagnosis of ASC (excluding Asperger syndrome) typically between 3 & 5 years of age, although parental concerns often by 18 months

Early identification should lead to early intervention

Reduction of stress and increased coping strategies for parents and other family members

Screening for autism in toddlers

Why?

Is Screening for Autism Is Screening for Autism

Desirable?Desirable?

No evidence that screening for autism can reduce

the risk of developing the condition

Psychological impact for an incorrect screening

result

Financial cost of screening – increased demand

for diagnostic services, interventions

Early SignsEarly Signs

Different developmental trajectories (Rogers,

2004)

Retrospective studies: orienting to name, gaze and

affect, joint attention

Ozonoff et al (2010): no behavioural differences at

6m

By 12m - differences in gaze to face and social

smiling

National Screening National Screening -- UKUK

Lack of standardised routine developmental screening

National Screening Committee examines evidence for:

• Condition in question

• Screening test

• Treatments available

• Effectiveness of overall screening programme

Present policy – ‘introduction of [ASD] screening cannot [currently] be recommended’

(NSC Child Health Subgroup, 2005)

Screening Test TerminologyScreening Test Terminology

Positive Predictive Value (PPV) = a / a + b

Sensitivity = a / a + c(How well does the screen detect cases?)

Specificity = d / b + d(How well does the screen discriminate cases from non-cases?)

Diagnosis +

Diagnosis -

Screen +

a

“True Positives”

b

“False Positives”

Screen

-

c

“False Negatives”

d

“True Negatives”

The The CHCHecklist for ecklist for AAutism in utism in

TToddlers (CHAT)oddlers (CHAT)Baron-Cohen et al (1992)

Based on:

– Health professionalobservation (HV, GP)

– Parental report

Expectation that majority of typically developing 18-month-olds would show joint attention and pretend play

Risk for autism may be revealed by absence of these key behaviours

The CHAT StudiesThe CHAT Studies

Baron-Cohen et al (1992)

• 18-month-olds (N=41) screened ‘at risk’ via CHAT

• By 30 months all ‘high risk’ infants were diagnosed with an ASD

Baird et al (2000)

• 16,235 children screened and followed up at age 7

• PPV high (83%), sensitivity poor (18%)

• CHAT missed 4 out of 5 children who later received diagnosis

• Sensitivity improved (38%) when one-stage screening procedure applied, still below acceptable levels

Why did the CHAT miss so Why did the CHAT miss so

many cases?many cases?

Wording – ‘has your child ever pointed?’

Focused primarily on joint attention

behaviours and pretend play

CHAT screening only took place at 18 months

Criteria to determine high and medium risk

groups may be too stringent

Other screening toolsOther screening tools

CSBS (Infant Toddler Checklist) – Wetherby

et al (2009): Community-based sample, n = 5,385.

PPV = 0.70, for communication delay including

autism (9 to 24-month-olds)

Modified-CHAT – Kleinman et al (2008): Mixed

high risk/low risk sample, n = 3,793. PPV = 0.36,

increased to 0.74 when combined with telephone

follow-up (16 to 30-month-olds)

Screening Tool for Two-year-olds (STAT) –Stone et al (2008): High-risk sample, n = 71. PPV =

0.56, for autism (12 to 23-month-olds)

Development of the Q-CHAT

Parent questionnaire – 18m HV check abandonedQ-CHAT – ‘Quantitative’ and ‘Quick’

25 items, scored on 5-point scale (0-4)

Range of total scores 0 – 100

Positive symptoms score more highly

Allows for a reduced rate of key behaviours

Takes into account the continuum nature of ASC

Includes additional items - language development, repetitive and sensory behaviours

Sample ItemSample Item

Does your child look at you when you call his/her name?

• Always - 0

• Usually - 1

• Sometimes - 2

• Rarely - 3

• Never - 4

14,000 Q-CHATs sent out to parents of 18 – 30month-olds in 3 PCTs in East of England

Returned questionnaires scored and stratifiedsampling to select children to be assessed:

All ‘high’ scorers (≥ 44)

50% of ‘high mid-range’ scorers (41 – 43)

25% of ‘low mid-range’ scorers (38 – 40)

~1% of ‘low’ scorers (≤ 37)

Took into account missing data in sampling

strategy

The Toddler Project

Methods:

Mostly home visits, within 2-3 months of initial Q-

CHAT

Child assessmentsADOS module 1 (play-based interactive diagnostic)

Mullen (verbal and nonverbal IQ)

Parent interviewsADI-R (diagnostic)

Vineland (adaptive behaviour)

Parent-child interaction

Repeat Q-CHAT

The Toddler ProjectAssessments:

Phase 1: First wave of Q-CHATs sent out in March 2008

So far approx 13,090 sent

3,823 returned (29%)

121 children assessed

Phase 2: Follow-up/Confirmation of diagnostic status:

Checklist for referral (Has child been referred or diagnosed with any condition since original Q-CHAT?)

ADOS, ADI-R, Vinelands, WASI

Follow-up assessments (4-5 year olds) by end of 2011

The Toddler ProjectTimetable:

Future Directions

1. Examine performance of Q-CHAT in sample

enriched with high scorers → Child

Development Centre

2. Identify ‘best’ Q-CHAT items and develop

referral guide for health/social care

professionals: HV, GPs, Nursery Staff

3. Engage with local NHS services to discuss

implementation and translation of research

findings into practice

High-risk sib studies

Recruitment of babies who have older sibs with

ASD enables prospective observation of the

emergence of autism (and BAP & typical

development)

Several studies in North America and one major

study (BASIS) in UK – longitudinal study involving

assessment at 4, 8, 14, 24 & 36m

High-risk sib studies

Emerging findings:

Recurrence rate may be >25% (depending on definition of

ASD)

Regression may be less common than suggested by

parental report

Group differences detectable at 6m, using technological approaches, such as eye tracking, but not until ~12m using

observation

This approach is clearly important in understanding the

“pre-history” of autism, but may not contribute so much to early identification/screening of low-risk children

Early intervention

There are now several RCTs of varied early

intervention approaches for children with autism

EIBI -------------ESDM------------PACT

Not surprisingly, the evidence shows that these

interventions have most impact on the skills and

behaviours that are targeted by the intervention

EIBI

Widely-evaluated, with varied findings – mostly

moderate to large effect sizes – gains in IQ scores

variable

Appears to work best with more able, less autistic

children

PACT

Green et al, (2010)

A large (N=150) RCT of a parent-training intervention

Strongest TE Weakest/No TE

parent-child child behaviour child behaviour childsynchrony with parent with researcher in

school

Overall

Little evidence regarding optimal age

Intensity tends to increase (short term) effectiveness

but risk of burn-out and plateau-ing after first year

High intensity parenting programmes no more

effective than low-intensity programmes for parents

already experiencing stress

Briefer, low intensity programmes can be effective

and offer access to a woder range of children and

families

g.pasco@ioe.ac.uk