Distinct temporal stages of infant brain processing associate with early versus later autism diagnosis

Background: The expression of autism traits sufficient to meet criteria for a diagnosis can occur early (by 3 years) or later (from mid-childhood onwards). It remains unknown whether variation in age of onset is due to clinical recognition or whether it reflects distinct biological pathways. One way of addressing this question is by investigating biological differences very early in development associated with age of onset. We use a prospective design to look at event related potentials to faces, one of the most robust biomarkers in autism. Methods: A sample of 102 infants (aged 6-10 months, 54% female) with an older autistic sibling had EEG recorded whilst viewing faces (faces versus noise; gaze towards versus away). Autism diagnostic assessments were conducted at three years and again in mid-childhood (aged 6-12 years), resulting in early diagnosed (at age 3; N=22), later diagnosed (at mid-childhood; N=21) and no autism (N=59) groups. Results: While a short latency response (P1) does not associate with autism outcome, a mid-latency component (N290) associates with early onset autism only, and a later latency component (P400) associates with both early and later onset autism. Conclusion: Temporal stages of face processing in infancy differentially associate with age of autism onset such that an earlier age of diagnosis is associated with earlier stage deviation within the event-related waveform. Early and later onset autism may represent different biological subtypes, with different early brain development, challenging the view of one etiological pathway and that variation in diagnostic age is due to clinical ascertainment.