Babies at risk for autism: Why, how, and what (do we know)? Mark Johnson

Superior Temporal Sulcus/GyrusLeft Frontal Operculum Fusiform Gyrus (blue) Orbitofrontal Cortex (red)

How does the social brain develop?

Superior Temporal Sulcus/GyrusLeft Frontal Operculum Fusiform Gyrus (blue) Orbitofrontal Cortex (red)

Infants at-risk for autism

Why? Research into early onset can get at causal factors Symptoms may be compounded during development Possibility of early intervention

Cause: The triad of impairment Social interaction Communication Restricted behaviors and interests

Compounding Symptoms In developmental disorders, initial symptoms can be compounded by atypical interactions with others and the environment Important to start early; e.g. over 1,000 hours of face-to-face social interaction in the first year.

Early intervention Medical research moving to prevention rather than cure Intervention programmes exist for young children already diagnosed Can we devise interventions for babies at highest risk, or that show early signs?

How? How can study the mind/brain of young babies? What at-risk groups are best for these studies What design of studies should we use?

How (can we study the mind of babies)?

Behavioral Testing

Looking measures in babies Preferential looking Habituation Eye-tracking

Eye-tracking in babies

EEG/Event-related potentials

ERP Results

Optical imaging (NIRS)

Optical Imaging (NIRS)

Infants at-risk Children with known genetic conditions (e.g. fragile-X; 30% have ASD) Children with other known medical conditions (e.g. tuberous sclerosis; 24% have ASD). Baby brothers and sisters of older children with autism (10%+).

Design of studies Longitudinal design with infant measures and assessment at 3 years Involves a 5 year-cycle and hundreds of babies Currently very few studies have reached this stage

So far…… Why? Cause, compounding, intervention How? New methods, study design What? - do we know so far?

Canadian study (Zwaigenbaum, Bryson and colleagues) siblings + low-risk controls Assessed at 6, 12, 18 and 24 months, with diagnostic assessment at 3 years AOSI: Autism Observation Scale for Infants

AOSI (Bryson et al. In press) Interactive, play-based measure of early signs of autism Attention & tracking Communication (e.g. social babbling) Social responses (e.g. peek-a-boo) Play (e.g. imitation) Motor control

AOSI (examples) Disengagement of visual attentionAnticipation Social babbling Imitation

Results so far No big differences at 6 months - most show typical social behaviours At 12 months differences appear in several measures (e.g. visual tracking, decreased eye contact, lack of imitation). By 18 months these differences are much clearer, but still only a 80-90% match with diagnosis at age 3 years

VERY preliminary conclusions Indicators are present in most children with ASD by 18 months Key features: early language, social communication, atypical attention and orienting Developmental trajectories vary: some show regression, others do not A need for more sensitive measures and methods

Infant Sibs in UK Collaboration with Tony Charman (ICH), Simon Baron-Cohen (Cambridge), Patrick Bolton (IOP) and others. Phase 0 (pilot), 31 baby siblings seen at 10 months. Currently seeing them at 3- 4 years old. Phase 1, planned for 100 babies seen at 6, 12, 24 and 36 months

Pilot (Phase 0) study Parent questionnaires about temperament, medical history etc Standardised tests (Mullen, Vineland) Physical growth measurements Lab measures of attention and perception

Preliminary findings Baby sibs differ as a group from low-risk controls in subtle measures of attention and social perception One possible reason - this is due to a few individuals (who may go on to be diagnosed) Another possibility - sibs do differ as a group, but the vast majority “recover from risk” to develop typically

National Infant Sibs Network Funded by Autism Speaks (UK) with other charities to start in 2008 Provides a platform for supporting and encouraging infant sibs work Central database with shared measures Meetings, workshops, and training

Holly Garwood Agnes Volein Leslie Tucker Gergely Csibra Mayada Elsabbagh Centre for Brain & Cognitive Development BabySibs team

Thanks to: -Collaborators Tony Charman, Patrick Bolton, Simon Baron-Cohen -All the babies and their families - Our funders MRC and Autism Speaks