Academic Journal
Complementary functional gradient and SFC analyses reveal network abnormalities in adolescent depression subtypes.
| Τίτλος: | Complementary functional gradient and SFC analyses reveal network abnormalities in adolescent depression subtypes. |
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| Συγγραφείς: | Zeng C; Guangyuan Mental Health Centre, Guangyuan, Sichuan, China. Electronic address: zengchengyan2025@163.com., Wu Z; Lanzhou University, Lanzhou, Gansu, China. Electronic address: wuzhg2025@lzu.edu.cn., Yang R; Guangyuan Mental Health Centre, Guangyuan, Sichuan, China. Electronic address: xyzdbxsb@163.com., Liu Q; Guangyuan Mental Health Centre, Guangyuan, Sichuan, China. Electronic address: liuqi20252025@163.com., Li S; Guangyuan Mental Health Centre, Guangyuan, Sichuan, China. Electronic address: lisijin202511@163.com., Yao Z; Lanzhou University, Lanzhou, Gansu, China. Electronic address: yaozj@lzu.edu.cn., Fu Y; Lanzhou University, Lanzhou, Gansu, China. Electronic address: fuyu@lzu.edu.cn., Wang X; Guangyuan Mental Health Centre, Guangyuan, Sichuan, China. Electronic address: wangxiuzhen202043@163.com. |
| Πηγή: | Behavioural brain research [Behav Brain Res] 2026 Oct 02; Vol. 514, pp. 116361. Date of Electronic Publication: 2026 Jul 08. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier/North-Holland Biomedical Press Country of Publication: Netherlands NLM ID: 8004872 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7549 (Electronic) Linking ISSN: 01664328 NLM ISO Abbreviation: Behav Brain Res Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Amsterdam, Elsevier/North-Holland Biomedical Press. |
| Ιατρικοί όροι (MeSH): | Major Depressive Disorder*/physiopathology , Major Depressive Disorder*/diagnostic imaging , Self-Injurious Behavior*/physiopathology , Self-Injurious Behavior*/diagnostic imaging , Nerve Net*/physiopathology , Nerve Net*/diagnostic imaging , Connectome*/methods , Brain*/physiopathology , Brain*/diagnostic imaging, Humans ; Magnetic Resonance Imaging ; Adolescent ; Female ; Male |
| Περίληψη: | Background: Adolescent major depressive disorder (MDD) emerges during a sensitive neurodevelopmental period and is frequently accompanied by non-suicidal self-injury (NSSI), a clinically important behavioral phenotype associated with affective dysregulation. Although prior resting-state fMRI studies have identified distributed functional abnormalities in adolescent MDD, it remains unclear whether MDD with NSSI is associated with alterations in macroscale functional organization, stepwise cross-network propagation, or both. We therefore combined functional gradient (FG) analysis and stepwise functional connectivity (SFC) to characterize group-related differences from the complementary perspectives of gradient-based functional organization and multi-step network propagation. Methods: Using resting-state fMRI data from 135 adolescents classified as healthy controls (HC), adolescents with major depressive disorder and non-suicidal self-injury (MDD-NSSI), and adolescents with major depressive disorder without NSSI (MDD-noNSSI), we estimated functional gradients based on the Schaefer-400 parcellation. Between-group differences in Gradient 1 (G1) and Gradient 2 (G2) were assessed using pairwise Welch's t-tests, followed by global BH-FDR correction across all 2400 ROI-wise tests. Bonferroni correction was additionally used as a conservative sensitivity analysis. To avoid circular seed selection, weighted SFC was performed using an a priori sgACC/BA25 seed set rather than ROIs selected from the gradient analysis. Stepwise propagation maps were computed from step 1 to step 7. For ROI-wise SFC comparisons, pairwise Welch's t-tests were performed within each contrast and step, followed by exploratory within-network BH-FDR correction separately within each canonical functional network. Results: Functional gradient analysis revealed distinct gradient profiles across the two patient groups. After global BH-FDR correction across 2400 ROI-wise tests, G1 showed extensive differences in MDD-noNSSI versus HC and in MDD-NSSI versus MDD-noNSSI, whereas the G1 difference between MDD-NSSI and HC was relatively limited. By contrast, G2 showed extensive and robust differences in MDD-NSSI versus HC and in MDD-NSSI versus MDD-noNSSI, while MDD-noNSSI showed a weaker G2 difference relative to HC. The exploratory sgACC/BA25-seeded SFC analysis showed HC-relative propagation abnormalities mainly involving limbic temporal pole and orbitofrontal parcels. Compared with HC, MDD-NSSI showed broader exploratory within-network-corrected limbic involvement and additional somatomotor reductions, whereas MDD-noNSSI showed a more focal left temporal pole propagation pattern. No direct SFC difference between MDD-NSSI and MDD-noNSSI survived exploratory within-network BH-FDR correction. Conclusion: FG findings provided direct evidence for different gradient-related profiles between adolescent MDD with and without NSSI, whereas sgACC/BA25-seeded SFC provided exploratory HC-relative propagation evidence. MDD-noNSSI was mainly associated with broad G1-related displacement, whereas MDD-NSSI was associated with G2-related redistribution and broader HC-relative limbic-cortical propagation abnormalities from the sgACC/BA25 seed. (Copyright © 2026 Elsevier B.V. All rights reserved.) |
| Competing Interests: | Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: Adolescent Depression; Functional Gradient; Stepwise Functional Connectivity; Subtype-specific Abnormalities |
| Entry Date(s): | Date Created: 20260708 Date Completed: 20260812 Latest Revision: 20260812 |
| Update Code: | 20260813 |
| DOI: | 10.1016/j.bbr.2026.116361 |
| PMID: | 42419463 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1872-7549 |
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| DOI: | 10.1016/j.bbr.2026.116361 |