<p>Feedback loops are central to the dynamics of mental disorder symptoms, serving as mechanisms that sustain and amplify symptoms over time. Despite their importance, the influence of feedback loop structures on symptom progression and persistence remains underexplored. Here, we introduce a general simulation-based framework for analyzing feedback-loop architecture in dynamical symptom networks and demonstrate it using a 9-node depression symptom network based on the PHQ-9. This study bridges this gap by analyzing a family of simulation models of symptom dynamics describing 98,304 directed networks compatible with empirically observed correlation symptom networks and their feedback loops. Systematic simulations of diverse network configurations revealed that while increasing the number of feedback loops elevates symptom levels, this effect plateaus due to the diminishing impact of overlapping loops. Additionally, networks with evenly distributed connectivity sustain higher symptom levels, necessitating the disruption of multiple feedback loops simultaneously to weaken the network’s cohesive structure and reduce symptom persistence. Empirical alignment using real-world clinical data supports these findings, demonstrating that frequently observed edges in network structures align with simulated configurations that drive high symptom levels. These results demonstrate that symptom severity and persistence are determined not merely by the presence of feedback loops but by their specific connections. These findings motivate intervention strategies that prioritize disrupting influential feedback structures and key connections rather than broadly reducing connectivity. By integrating computational modeling and empirical analysis, this study advances our understanding of symptom persistence and offers insights for designing targeted interventions to mitigate symptom severity and relapse risk.</p>