Functional brain connectome-transcriptional landscape linking to transdiagnostic factors of psychopathological symptoms

Abstract Transdiagnostic factors are considered promising in elucidating the etiological underpinnings of psychiatric comorbidities, especially in anxiety and depression. However, their symptom-centered neurobiological substrates, encompassing the genetic macro-micro-molecular brain functional landscape, remain elusive. Here, we develop edge-centric functional brain connectome-based predictive models for transdiagnostic factors of anxiety and depression symptoms (sTDF). These factors are estimated from nonlinear Gaussian topological schemes in a nationwide sample and a twin dataset. Edge-centric connectome was found to be reproducible and generalizable neural signatures for the sTDF, showing high sensitivity in neurally representing the sTDF from edge-centric similarity patterns of attention/frontoparietal networks. Such edge-centric signatures were found moderately heritable. Genetic transcriptional analyses further revealed the biological enrichment for gene expression patterns of these edge-centric connectome emerging into vessel systems and metabolism of CMRO2 for sTDF, especially for cerebellar development in late-childhood-to-young-adulthood. Our findings shed lights on the neurobiological architectures of sTDF by clarifying edge-centeric connectome-transcriptional signature.