Major depressive disorder recurrence and medication status shape brain network topology
Introduction: Major depressive disorder (MDD) is a highly prevalent and disabling psychiatric disorder. Human neuroimaging studies increasingly frame its neurobiological substrate in terms of alterations of large-scale brain network organization. Resting-state fMRI findings broadly align with this view, yet remaining highly heterogeneous, reflecting both clinical and analytic variability.…
Major depressive disorder (MDD) is a common and debilitating mental health condition. Neuroimaging research suggests that MDD involves changes in the brain's large-scale network architecture. However, existing studies have produced inconsistent results, likely due to differences in study design and analytical techniques. In this study, researchers employed novel topological data analysis methods to investigate how the brain's functional connectivity patterns relate to MDD.
The study analyzed data from 1,490 participants, including 776 individuals with MDD and 714 healthy controls. Researchers computed functional connectivity matrices using Pearson correlations between regions defined by the Power-264 atlas and harmonized the data across sites with CovBat. They then applied topological data analysis to examine whole-brain network organization across various connectivity thresholds using the B and B metrics.
The B metric quantifies global network integration, while the B metric assesses the presence of higher-order cycles across scales. Individuals with MDD exhibited significantly higher B-AUC values compared to controls, indicating altered global integration patterns. Importantly, B-AUC did not differ based on illness course, duration, or symptom severity.
However, B-AUC increased progressively across illness courses, with the highest values observed in recurrent depression. This pattern was driven by an increased number of one-dimensional cycles rather than longer-lasting cycles.
Medication status also influenced B-AUC values, with unmedicated single-episode and medicated recurrent MDD showing elevated values. Anatomical decomposition revealed that these higher-order alterations were primarily driven by changes in inter-network configurations spanning multiple large-scale functional systems.
These findings suggest that MDD is associated with altered multiscale brain network organization. Specifically, individuals with MDD exhibit less compact global integration and a higher prevalence of cross-network hole-defining cycles. Furthermore, these features vary systematically with illness course and current medication status.
The researchers conclude that topology-informed measures may capture clinically relevant variability in brain organization in depression, providing valuable insights into the neural mechanisms underlying this disorder.
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