MMDD: A Multimodal Multitask Dynamic Disentanglement Framework for Robust Major Depressive Disorder Diagnosis Across Neuroimaging Sites.

Background/

Objectives

Major Depressive Disorder (MDD) is a severe psychiatric disorder, and effective, efficient automated diagnostic approaches are urgently needed. Traditional methods for assessing MDD face three key challenges: reliance on predefined features, inadequate handling of multi-site data heterogeneity, and suboptimal feature fusion. To address these issues, this study proposes the Multimodal Multitask Dynamic Disentanglement (MMDD) Framework.

Methods

The MMDD Framework has three core innovations. First, it adopts a dual-pathway feature extraction architecture combining a 3D ResNet for modeling gray matter volume (GMV) data and an LSTM-Transformer for processing time series data. Second, it includes a Bidirectional Cross-Attention Fusion (BCAF) mechanism for dynamic feature alignment and complementary integration. Third, it uses a Gradient Reversal Layer-based Multitask Learning (GRL-MTL) strategy for enhancing the model's domain generalization capability.

Results

MMDD achieved 77.76% classification accuracy on the REST-meta-MDD dataset. Ablation studies confirmed that both the BCAF mechanism and GRL-MTL strategy played critical roles: the former optimized multimodal fusion, while the latter effectively mitigated site-related heterogeneity. Through interpretability analysis, we identified distinct neurobiological patterns: time series were primarily localized to subcortical hubs and the cerebellum, whereas GMV mainly involved higher-order cognitive and emotion-regulation cortices. Notably, the middle cingulate gyrus showed consistent abnormalities across both imaging modalities.

Conclusions

This study makes two major contributions. First, we develop a robust and generalizable computational framework for objective MDD diagnosis by effectively leveraging multimodal data. Second, we provide data-driven insights into MDD's distinct neuropathological processes, thereby advancing our understanding of the disorder.