Distinct Temporal Stages of Infant Brain Processing Associate With Early Versus Later Autism Diagnosis

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 reflects distinct biological pathways. One way of addressing this question is by investigating biological differences very early in development associated with a later age of diagnosis. We use a prospective family history design to look at event-related potentials to faces, one of the most robust biomarkers in autism. A sample of 102 infants (aged 6-10 months, 54% female) with an older autistic sibling had an EEG recorded whilst viewing faces (faces vs. noise; gaze toward vs. away). Autism diagnostic assessments were conducted at 3 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 in early or mid-childhood (N = 59) groups. We found that while early-stage visual processing (P100) does not associate with autism outcome, speed of structural face-versus-noise processing (N290) is slower in early-onset autism only, and semantic processing (P400) is altered in both early- and later-onset autism. Thus, 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 subtypes, challenging the view of one etiological pathway and that variation in diagnostic age is solely due to clinical ascertainment. SUMMARY: Temporal stages of face processing in infancy differentially associate with age of autism onset. N290 is slower in early-onset autism, indicating an earlier stage neural deviation. The later occurring P400 is altered in both early- and later-onset autism. Early and later-onset autism may represent distinct biological subtypes.