Transdiagnostic and Diagnosis-Specific Morphological Similarity Related Transcriptional Profile in Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder

Objective: Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are both highly heritable developmental psychiatric disorders and exhibit a high degree of comorbidity. Our objective is to enhance understanding of the transdiagnostic and diagnosis-specific structural alterations and related cellular and genetic pathophysiological mechanisms between ADHD and ASD. Method: We used structural magnetic resonance imaging data of 247 subjects from the publicly available 1000 Functional Connectomes Project, including 91 individuals with ADHD, 49 individuals with ASD, and 107 age- and sex-matched controls. We performed morphological similarity networks (MSN) and gene transcriptional profile analysis on these image data to identify the anatomical changes and MSN-related genes. Enrichment analysis was further conducted on ADHD/ASD risk genes and MSN-related genes. Results: Individuals with ADHD showed the diagnosis-specific MSN changes distributing in areas related to high-level cognitive functions, whereas ASD had MSN changes in areas related to language comprehension and spatial location. ADHD and ASD exhibited the transdiagnostic morphological increase in the right middle temporal gyrus. Gene transcriptional profile analysis showed enrichment of ADHD and ASD risk genes in more than 10 biological processes, primarily including function of synapse transmission and development. Genes in excitatory and inhibitory neurons also enriched in pathways with similar function. Conclusion: The transdiagnostic morphological dedifferentiation in the right middle temporal gyrus might indicate the shared motion impairments in ADHD and ASD. Evidence from the transcription of MSN-related genes further indicates a potential imbalance in excitatory and inhibitory neural pathways in ADHD and ASD. Diversity & Inclusion Statement: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. We worked to ensure sex balance in the selection of non-human subjects. We worked to ensure diversity in experimental samples through the selection of the cell lines. We worked to ensure diversity in experimental samples through the selection of the genomic datasets. Diverse cell lines and/or genomic datasets were not available. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list.