Transdiagnostic subtyping of males with developmental disorders using cortical characteristics

• Published in: NeuroImage clinical 2020-01, Vol.27, p.102288-102288, Article 102288
• Main Authors: Itahashi, Takashi, Fujino, Junya, Hashimoto, Ryu-ichiro, Tachibana, Yoshiyuki, Sato, Taku, Ohta, Haruhisa, Nakamura, Motoaki, Kato, Nobumasa, Eickhoff, Simon B., Cortese, Samuele, Aoki, Yuta Y.
• Format: Article
• Language: English
• Subjects: Adult; Attention Deficit Disorder with Hyperactivity - pathology; Attention Deficit Disorder with Hyperactivity - physiopathology; Attention-deficit/hyperactivity disorder; Autism spectrum disorder; Autism Spectrum Disorder - pathology; Autism Spectrum Disorder - physiopathology; Brain - pathology; Brain - physiopathology; Brain Mapping; Cortical thickness; Female; Humans; HYDRA; Image Processing, Computer-Assisted - methods; Magnetic Resonance Imaging - methods; Male; Middle Aged; Regular; Subtype
• ISSN: 2213-1582; 2213-1582
• DOI: 10.1016/j.nicl.2020.102288

•Overlapping diagnosis and within-diagnosis heterogeneity was often reported in ASD.•ASD and ADHD were subtyped regardless of diagnosis using cortical characteristics.•The analysis revealed the number of subtypes as two.•The boundary of the subtypes did not match the diagnostic boundary.•The membership of subtypes was robust against the choice of an atlas. Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are biologically heterogeneous and often co-occur. As within-diagnosis heterogeneity and overlapping diagnoses are challenging for researchers and clinicians, identifying biologically homogenous subgroups, independent of diagnosis, is an urgent need. MRI data from 148 adult males with developmental disorders (99 primary ASD, mean age = 31.7 ± 8.0, 49 primary ADHD; mean age = 31.7 ± 9.6) and 105 neurotypical controls (NTC; mean age = 30.6 ± 6.8) were analyzed. We extracted mean cortical thickness (CT) and surface area (SA) values using a functional atlas. Then, we conducted HeterogeneitY through DiscRiminant Analysis (HYDRA) to transdiagnostically cluster and classify individuals. Differences in diagnostic likelihood and clinical symptoms between subtypes were tested. Sensitivity analyses tested the stability of the number of subtypes and their membership by excluding 13 participants diagnosed with both ASD and ADHD and by using a different atlas. In relation to both CT and SA, HYDRA identified two subtypes. The likelihood of ASD or ADHD was not significantly different from the chance of belonging to any of these two subtypes. Clinical characteristics did not differ between subtypes in either CT or SA based analyses. The high consistency in membership was replicated when utilizing a different atlas or excluding people with dual diagnoses in CT (dice coefficients > 0.94) and in SA (>0.88). Although the brain-derived subtypes do not match diagnostic groups, individuals with developmental disorders were successfully and stably subtyped using either CT or SA.