HDGNN-Mamba2: Mamba-Based Spatiotemporal Heterogeneous Dynamic Graph Neural Network for Major Depressive Disorder Classification

Background: Major depressive disorder (MDD) affects 332 million people worldwide, yet diagnosis remains reliant on subjective clinical interviews with substantial inter-rater variability. Objective neuroimaging model-attributed regions offer a path toward precision psychiatry, but existing computational approaches often lack clinical interpretability. Methods: We propose HDGNN-Mamba2, a Mamba-based spatiotemporal heterogeneous dynamic graph neural network. A hybrid Mamba2-GNN block with cross-attention fusion is developed to capture individual spatiotemporal contextual features and identify model-attributed regions. A heterogeneous global graph block with dynamic edge updating is constructed, integrating individual brain features with non-imaging phenotypic information (sex, age, education) to extract embeddings through inter-individual relationship modeling. Heterogeneous Graph Supervised Contrastive Learning is integrated to enhance discriminative capacity. Results: Evaluated on 533 subjects from the REST-meta-MDD dataset, HDGNN-Mamba2 achieved 83.88% accuracy, 86.52% sensitivity, and 80.85% specificity in ten-fold cross-validation. The identified model-attributed regions include the anterior cingulate cortex, parahippocampal gyrus, and thalamus. Conclusions: HDGNN-Mamba2 demonstrates competitive performance as an algorithmic framework for MDD classification, offering complementary architectural advantages in spatiotemporal fusion and interpretable region identification.