Stratifying the autistic phenotype using electrophysiological indices of social perception

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by difficulties in social communication, but also great heterogeneity. To offer individualized medicine approaches, we need to better target interventions by stratifying autistic people into subgroups with different biological profiles and/or prognoses. We sought to validate neural responses to faces as a potential stratification factor in ASD by measuring neural (electroencephalography) responses to faces (critical in social interaction) in N = 436 children and adults with and without ASD. The speed of early-stage face processing (N170 latency) was on average slower in ASD than in age-matched controls. In addition, N170 latency was associated with responses to faces in the fusiform gyrus, measured with functional magnetic resonance imaging, and polygenic scores for ASD. Within the ASD group, N170 latency predicted change in adaptive socialization skills over an 18-month follow-up period; data-driven clustering identified a subgroup with slower brain responses and poor social prognosis. Use of a distributional data-driven cutoff was associated with predicted improvements of power in simulated clinical trials targeting social functioning. Together, the data provide converging evidence for the utility of the N170 as a stratification factor to identify biologically and prognostically defined subgroups in ASD. N170 latency to faces relates to fusiform activity and ASD genetics, predicts social prognosis, and could improve power in clinical trials. The heterogeneity observed in people with autism spectrum disorder (ASD) highlights the need for better stratification methods. Here, Mason et al. evaluated the use of the speed of early-stage face processing (N170 latency) for clinical stratification and prognosis in participants with ASD and age-matched neurotypical individuals. N170 latency was slower in individuals with ASD and correlated with response to faces measured with fMRI and with polygenic score. Among participants with ASD, the N170 values stratified people according to socialization prognosis and improved power in a simulated clinical trial. The results suggest that including N170 evaluation in participant stratification might help the design and development of personalized therapies for ASD.