Bridging molecules and connectome: network biomarkers guided by neurotransmitter architecture in major depressive disorder

; ρ = -0.217) and dopaminergic markers, including the dopamine transporter (DAT) and dopamine receptors (D1 and D2; ρ range: -0.204 to -0.227). To translate these mechanistic insights into individual-level predictions, we developed the Neurotransmitter Transporter/Receptor-Annotated Connectome Classification Model (NTR-CCM), which incorporates molecular maps as biological priors to guide feature selection. The NTR-CCM achieved superior diagnostic performance in the discovery cohort (area under the curve [AUC] = 0.83-0.86) and maintained robust generalization in the external validation cohort (AUC = 0.73-0.75). These results indicate that macroscale connectome reorganization in MDD is spatially constrained by the brain's underlying neurochemical architecture. By bridging molecular and systems scales, the NTR-CCM provides a high-performing and mechanistically interpretable framework for precision psychiatry.