Cortical signatures in behaviorally clustered autistic traits subgroups: a population-based study.

Extensive heterogeneity in autism spectrum disorder (ASD) has hindered the characterization of consistent biomarkers, which has led to widespread negative results. Isolating homogenized subtypes could provide insight into underlying biological mechanisms and an overall better understanding of ASD. A total of 1093 participants from the population-based "Healthy Brain Network" cohort (Child Mind Institute in the New York City area, USA) were selected based on score availability in behaviors relevant to ASD, aged 6-18 and IQ >= 70. All participants underwent an unsupervised clustering analysis on behavioral dimensions to reveal subgroups with ASD traits, identified by the presence of social deficits. Analysis revealed three socially impaired ASD traits subgroups: (1) high in emotionally dysfunctional traits, (2) high in ADHD-like traits, and (3) high in anxiety and depressive symptoms. 527 subjects had good quality structural MRI T1 data. Site effects on cortical features were adjusted using the ComBat method. Neuroimaging analyses compared cortical thickness, gyrification, and surface area, and were controlled for age, gender, and IQ, and corrected for multiple comparisons. Structural neuroimaging analyses contrasting one combined heterogeneous ASD traits group against controls did not yield any significant differences. Unique cortical signatures, however, were observed within each of the three individual ASD traits subgroups versus controls. These observations provide evidence of ASD traits subtypes, and confirm the necessity of applying dimensional approaches to extract meaningful differences, thus reducing heterogeneity and paving the way to better understanding ASD traits.