ArticleBMC psychiatry2026
Distance-related functional connectivity alterations in first-episode, drug-naïve major depressive disorder: a resting-state fMRI study with atlas-based neurotransmitter correlates.
Article in BMC psychiatry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundMajor depressive disorder (MDD) has been associated with large-scale functional dysconnectivity, yet it remains unclear whether these abnormalities differ as a function of anatomical distance. We investigated distance-related functional connectivity strength (FCS) alterations in first-episode, drug-naïve MDD and examined whether their spatial distribution corresponds to atlas-based neurotransmitter receptors/transporters profiles.
methodsResting-state functional MRI data were acquired from 191 patients with first-episode, drug-naïve MDD and 130 healthy controls. Whole-brain global, long-range, and short-range FCS were quantified voxel-wise. Distance-constrained seed-based connectivity analyses were performed to characterize the circuit-level contributions underlying abnormal FCS findings. To provide a molecular context, regional maps of FCS abnormalities were compared with neurotransmitter receptors/transporters distributions derived from a publicly available positron emission tomography atlas.
resultsCompared with healthy controls, patients with MDD showed reduced long-range FCS in the left orbital superior frontal gyrus and left medial superior frontal gyrus, together with increased short-range FCS in the right inferior parietal lobule. Seed-based analyses indicated that reduced long-range FCS was mainly related to weaker long-range connectivity between the left orbital superior frontal gyrus and right inferior temporal gyrus, and between the left medial superior frontal gyrus and right hippocampus. Increased short-range FCS in the right inferior parietal lobule was associated with stronger short-range connectivity with the right inferior frontal operculum, right superior temporal gyrus, and left paracentral lobule. The spatial pattern of FCS abnormalities showed significant correspondence with atlas-based neurotransmitter receptors/transporters distributions; short-range abnormalities spatially covaried with an atlas-derived regional excitation-inhibition balance.
conclusionsFirst-episode, drug-naïve MDD is characterized by a distance-related pattern of reduced long-range prefrontal connectivity and increased short-range parietal connectivity. Atlas-based molecular mapping provides a biologically informed, population-level spatial context for these macroscale functional abnormalities.
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