Gray Matter Asymmetry Alterations in Children and Adolescents with Comorbid Autism Spectrum Disorder and Attention-deficit/hyperactivity Disorder

Despite the high coexistence of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) (ASD + ADHD), the underlying neurobiological basis of this disorder remains unclear. Altered brain structural asymmetries have been verified in ASD and ADHD, respectively, making brain asymmetry a candidate for characterizing this coexisting disorder. Here, we measured the gray matter (GM) volume asymmetry in ASD + ADHD versus ASD without ADHD (ASD-only), ADHD without ASD (ADHD-only), and typically developing controls (TDc). High-resolution T1-weighted data from 48 ASD + ADHD, 63 ASD-only, 32 ADHD-only, and 211 matched TDc were included in our study. We also assessed brain-behavior relationships and the effects of age on GM asymmetry. We found that there were both shared and disorder-specific GM volume asymmetry alterations in ASD + ADHD, ASD-only, and ADHD-only compared with TDc. This finding demonstrates that ASD + ADHD is neither an endophenocopy nor an additive pathology of ASD and ADHD, but an entirely different neuroanatomical pathology. In addition, ASD + ADHD displayed altered GM volume asymmetries in the prefrontal regions responsible for executive function and theory of mind compared with ASD-only. We also found significant effects of age on GM asymmetry. The present study may provide structural insights into the neural basis of ASD + ADHD.