Parsing neurobiological heterogeneity in treatment-resistant depression using brain network localization

BACKGROUND: Treatment-resistant depression (TRD) imposes greater illness burden and worse clinical outcomes than its non-TRD counterpart. Previous neuroimaging research on the brain substrates of TRD and non-TRD has yielded divergent results, which may be reconciled by updated network localization. METHODS: We initially synthesized published neuroimaging literature to identify brain locations with structural or functional differences between TRD vs. healthy controls (HC), non-TRD vs. HC, and TRD vs. non-TRD. By combining these affected brain locations with large-scale discovery (1113 healthy individuals) and validation (1093 healthy individuals and 255 MDD patients) resting-state functional MRI datasets, we then employed novel functional connectivity network mapping to construct three brain networks. RESULTS: The brain network of TRD vs. HC comprised a broadly distributed set of brain regions predominantly implicating the canonical ventral attention, subcortical, default, somatomotor, and frontoparietal networks. The network of non-TRD vs. HC also manifested as a widely distributed pattern of regions primarily involving the default, limbic, and frontoparietal networks. The network of TRD vs. non-TRD mainly implicated the ventral attention and default networks. CONCLUSIONS: Our findings can contribute to elucidating the differential neuropathological processes underlying TRD and non-TRD.