Cortical Thickness in Autism Spectrum Disorder Is Modulated by Comorbid Attention-Deficit Hyperactivity Disorder

Theoretical Background: Autism spectrum disorder (ASD) is a common neurodevelopmental condition with a highly heterogeneous phenotype that includes several comorbid conditions, such as attention-deficit hyperactivity disorder (ADHD). Both ASD and ADHD are accompanied by atypical brain development that affects several markers of brain anatomy. For example, measures of cortical thickness (CT) have been found to be atypical in both conditions and in several spatially distributed neural networks. The influence of comorbid symptoms is, however, often ignored in conventional neuroimaging studies that typically examine the neuroanatomy of ASD relative to typically developing (TD) controls. It therefore remains largely unknown to what degree neuroanatomical differences in ASD individuals with an additional diagnosis of ADHD differ from those that only display core ASD symptomatology. Objective: In the present study, we examined to what degree the cortical thickness of ASD is modulated by the existence of a comorbid diagnosis of ADHD in a sample of individuals with ASD (with and without ADHD) and neurotypical controls. Method: Our sample consisted of 101 participants (11 - 19 years), including (a) 60 individuals with ASD (41 without ADHD, 19 with ADHD) and (b) 41 healthy controls matched for gender, age, and full-scale intelligence quotient (IQ). We examined vertex-wise estimates of CT based on structural T1-weighted magnetic resonance imaging scans. Initially, we examined our scientific question using an ANOVA, with ASD and ADHD as fixed-effect variables based on diagnostic labels, an ASD-by-ADHD interaction term, and gender, age, IQ, and mean CT as covariates. In a subsequent analysis, we explored whether differences in CT between ASD individuals with and without ADHD are parametrically modulated by the severity of ADHD symptoms. Here, we used Pearson's correlation coefficients to establish associations between ADHD symptomatology and neuroanatomical differences in CT. Results: Significant neuroanatomical differences for the main effect of ASD were observed in the left posterior cingulate cortex (PCC), where CT was increased in individuals with ASD. Further, ASD individuals with comorbid ADHD as compared with controls and ASD individuals without ADHD exhibited significantly increased CT in the right PCC and right parieto-occipital regions, while a decreased CT was observed in left fronto-central regions. This fronto-central cluster showed a significant negative correlation with ADHD symptom severity. We further observed significant differences between ASD individuals with and without ADHD in the left PCC, lingual gyrus, and precuneus. Discussion and Conclusion: Our study therefore suggests that the neuroanatomy of ASD is modulated by the co-occurrence of ADHD symptoms, which should be accounted for in future studies examining the neuroanatomical underpinnings of ASD, and in studies attempting to stratify ASD individuals.