Brain-Body Signatures of Trait Anxiety Uniquely Characterized by Functional Dynamics, Allostatic Load and Gene Expression

Trait anxiety is an individual disposition marked by heightened anticipation of potential threats under uncertainty. It has been associated with allostatic load, the cumulative physiological cost of chronic stress, suggesting that enduring anxiety vulnerability emerges from brain–body interactions across multiple scales. Yet these domains have largely been examined separately and the temporal dynamics of brain activity remain underexplored. Using data from healthy young adults (LEMON cohort, N = 120), we implemented a graph-attention framework integrating low-frequency (slow-4 and slow-5) fMRI dynamics, structural connectivity and systemic biomarkers through cross-modal attention to predict individual trait anxiety outcome (The State-Trait Anxiety Inventory). Temporal modeling significantly enhanced prediction compared with static or amplitude-based features, highlighting the importance of time-resolved neural information. Model-derived importance mapping identified the limbic and visual systems as core predictive networks. Dynamic functional connectivity revealed that higher trait anxiety was associated with longer occupancy of states marked by strong limbic–default-mode–frontoparietal coupling and shorter occupancy of visually decoupled states. Metabolic and immune markers further contributed to prediction and transcriptomic enrichment linked these networks to neurodevelopmental and synaptic signaling pathways. Together, these findings delineate a temporally dynamic brain and body architecture underlying stable anxiety vulnerability.