Title: Mapping Neurophysiological Subtypes of Major Depressive Disorder Using Normative Models of the Functional Connectome.
Session: Oral Session
Speaker: Xiaoyi Sun
Abstract: Background: Major depressive disorder (MDD) is a highly heterogeneous disorder that typically emerges in adolescence and can occur throughout adulthood. Quantitatively uncovering the heterogeneity of individual functional connectome abnormalities in MDD and identifying reproducibly distinct neurophysiological MDD subtypes across the lifespan, which could provide promising insights for precise diagnosis and treatment prediction, are still lacking.Methods: Leveraging resting-state functional MRI data from 1,148 MDD patients and 1,079 healthy controls (ages 11-93), we conducted the largest multisite analysis to date for neurophysiological MDD subtyping. We first characterized typical lifespan trajectories of functional connectivity strength based on the normative model and quantitatively mapped the heterogeneous individual deviations among MDD patients. Then, we identified neurobiological MDD subtypes using an unsupervised clustering algorithm and evaluated intersite reproducibility. Finally, we validated the subtype differences in baseline clinical variables and longitudinal treatment predictive capacity.Results: Our findings indicated great intersubject heterogeneity in the spatial distribution and severity of functional connectome deviations among MDD patients, which inspired the identification of two reproducible neurophysiological subtypes. Subtype 1 showed severe deviations with positive deviations in the default mode, limbic, and subcortical areas and negative deviations in the sensorimotor and attention areas. Conversely, subtype 2 showed a moderate but converse deviation pattern. More importantly, subtype differences were observed in depressive item scores and predictive ability of baseline deviations for antidepressant treatment outcomes.Conclusions: These findings shed light on our understanding of different neurobiological mechanisms underlying the clinical heterogeneity of MDD and are essential for developing personalized treatments for this disorder.
