Unraveling spatiotemporal dynamics in transdiagnosis subtypes of major depressive disorder and bipolar disorder: insights from co-activation patterns and treatment response

Major depressive disorder (MDD) and bipolar disorder (BD) share numerous overlapping symptoms and clinical features, both classified as mood disorders (MD). Despite the proposal of several transdiagnostic subtypes, the dynamic features and network-level neurobiological mechanisms underlying these subtypes remain poorly understood. In the current study, data from two independent cohorts were used to investigate the spatiotemporal features of brain activity. Cohort1 included 112 MD patients and 142 healthy controls (HC) for cross-sectional comparison, while Cohort2 comprised 423 MD patients who underwent MRI scanning before and after one week in-hospital treatment. Initially, two subtypes were identified based on their amplitude of low-frequency fluctuation (ALFF) maps, and their brain spatiotemporal dynamics were further explored using co-activation patterns (CAPs). Four recurrent CAP states were identified: CAP2 and CAP3 were primarily associated with default mode network (DMN), while CAP1 and CAP4 were associated with frontoparietal network (FPN). Results showed that Subtype1 exhibited higher occurrence, persistence, and transition probabilities of DMN-related states, along with lower dynamics in FPN-related states. In contrast, Subtype2 showed higher occurrence and persistence in FPN-related states. Further analysis revealed that these dynamic features tended to revert toward normal states after one week treatment. Moreover, the dynamic characteristics in Subtype1 were associated with higher suicidality and lower agitation symptoms, while those in Subtype2 were correlated with somatic anxiety and systemic symptoms. Our study provides insights into the spatiotemporal dynamics of brain intrinsic states in different subtypes of MD, revealing the variations in MD subtypes and treatment response from a dynamic perspective and offering a pathway for further elucidation of their underlying biological mechanisms.