ArticleCNS neuroscience & therapeutics2026
Association of Left Angular Gyrus-Right Middle Frontal Gyrus Functional Connectivity With Insomnia Severity in Major Depressive Disorder: Evidence From the DIRECT Consortium.
Article in CNS neuroscience & therapeutics, 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
backgroundIdentifying neuroimaging correlates of insomnia severity could provide insights into the underlying biological mechanisms of major depressive disorder (MDD). However, related findings remain inconsistent, and the functional connectivity patterns associated with insomnia severity are unclear.
methodsThis study analyzed resting-state fMRI data from 385 patients with MDD and 336 healthy controls (HCs) sourced from nine sites of the DIRECT Consortium. Patients were stratified into high insomnia (MDDHI; HAMD insomnia subscale ≥ 4, n = 226) and low insomnia (MDDLI; HAMD insomnia subscale ≤ 3, n = 159) groups. Among patients with MDDHI, MDDLI and HCs, we first examined network-level functional connectivity abnormalities using the Craddock 200 atlas, and then local brain function was assessed using the amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo) and degree centrality (DC). Finally, we adopted multiple analytical approaches to verify the robustness of the significant findings.
resultsCompared to both patients with MDDHI and HCs, patients with MDDLI exhibited significantly reduced functional connectivity between the left angular gyrus (AG) and the right middle frontal gyrus (MFG). Both patients with MDDHI and MDDLI showed significantly decreased ALFF and ReHo values relative to HCs across multiple brain regions, including bilateral angular gyrus/precuneus/cerebellum posterior lobe and so on. For DC, patients with MDDHI showed significantly decreased values relative to HCs in all identified clusters, whereas patients with MDDLI showed significant DC reductions in a subset of these clusters. When these results were validated using multiple analytical approaches, the primary findings remained consistent.
conclusionsReduced functional connectivity between the left AG and the right MFG may be a candidate neuroimaging marker for sleep-related heterogeneity in MDD. However, widespread local brain function abnormalities may reflect core depressive pathology of MDD. These findings advance our understanding of the neurobiology of MDD.
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