Transdiagnostic network alterations and associated neurotransmitter signatures across major psychiatric disorders in adolescents: Evidence from edge-centric analysis of time-varying functional brain networks

Background: Adolescence is a pivotal phase marked by heightened vulnerability to the onset of psychiatric disorders. However, there are few transdiagnostic studies of dynamic brain networks across major psychiatric disorders during this phase. Methods: We collected resting-state functional MRI data from 189 adolescent patients (61 with bipolar disorder, 73 with major depressive disorder, and 55 with schizophrenia) and 181 healthy adolescents. Functional networks were constructed using a state-of-art edge-centric dynamic functional connectivity (DFC) approach. Results: Four DFC states were identified for the healthy adolescents that were related to different behavioral and cognitive terms. Disorder-related alterations were observed in two states involving motor and somatosensory processing and one state involving various cognitive functions. Regardless of the state, the three patient groups exhibited lower FC that were mainly involved in edges between different functional subsystems and were predominantly linked to regions in the somatomotor network. The patients with major depressive disorder additionally showed increased FC that were primarily linked to default mode regions. Graph-based network analysis revealed different patterns of disrupted small-world organization and altered nodal degree in the disorders in a state-dependent manner. The nodal degree alterations were correlated with the concentration of various neurotransmitters. Intriguingly, the noradrenaline concentration was engaged in the nodal degree alterations in each patient group. Finally, decreased FC involving regions in the somatomotor network showed significant correlations with clinical variables in the major depressive disorder patients. Conclusion: These findings may help understand the developmental pathways associated with the heightened vulnerability to major psychiatric disorders during adolescence.