Disrupted brain connectivity networks in drug-naive, first-episode major depressive disorder
Abstract
Background Neuroimaging studies have shown that major depressive disorder (MDD) is accompanied by structural and functional abnormalities in specific brain regions and connections; yet, little is known about alterations of the topological organization of whole-brain networks in MDD patients.Methods Thirty drug-naive, first-episode MDD patients and 63 healthy control subjects underwent a resting-state functional magnetic resonance imaging scan. The whole-brain functional networks were constructed by thresholding partial correlation matrices of 90 brain regions, and their topological properties (e.g., small-world, efficiency, and nodal centrality) were analyzed using graph theory-based approaches. Nonparametric permutation tests were further used for group comparisons of topological metrics.Results Both the MDD and control groups showed small-world architecture in brain functional networks, suggesting a balance between functional segregation and integration. However, compared with control subjects, the MDD patients showed altered quantitative values in the global properties, characterized by lower path length and higher global efficiency, implying a shift toward randomization in their brain networks. The MDD patients exhibited increased nodal centralities, predominately in the caudate nucleus and default-mode regions, including the hippocampus, inferior parietal, medial frontal, and parietal regions, and reduced nodal centralities in the occipital, frontal (orbital part), and temporal regions. The altered nodal centralities in the left hippocampus and the left caudate nucleus were correlated with disease duration and severity.Conclusions These results suggest that depressive disorder is associated with disruptions in the topological organization of functional brain networks and that this disruption may contribute to disturbances in mood and cognition in MDD patients.
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The areas of FCS decrease are prominent hubs of global and local functional connectivity, and age-related decrease could underlie performance decline in working memory and visual sustained attention.
“The areas of FCS decrease are the prominent hubs of global and local functional connectivity, and the age-related decrease could underlie the performance decline in working memory and visual sustained attention, which are the most affected cognitive functions that occur with aging [39-41].”
From Mapping neurophysiological subtypes of major depressive disorder using normative models of the functional connectome (2023) · cites this paper as [41]
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“Depression is associated with increased nodal centralities (65) and elevated within-network DMN connectivity at rest (219) and during engagement in externally focused thought (220), both of which manifest in excessive self-referential processing and maladaptive rumination.”
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- Authors
- Zhang, J., Wang, J., Wu, Q., Kuang, W., Huang, X., He, Y., & Gong, Q.
- Affiliations
- West China Medical Center of Sichuan University (CN)
- Beijing Normal University (CN)
- Sichuan University (CN)
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2011-08
- Volume
- 70
- Issue
- 4
- Pages
- 334-342
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2076380208
- Cited by
- 951
- References
- 87
- Citations by year
- 2026: 42 · 2025: 60 · 2024: 72 · 2023: 64 · 2022: 76 · 2021: 100 · 2020: 67 · 2019: 73 · 2018: 68 · 2017: 72 · 2016: 60 · 2015: 55 · 2014: 44 · 2013: 64 · 2012: 28
- FWCI
- 22.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation (81030027, 81030028, 30870667)
- National Basic Research Program
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Mental Health Research Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- major depressive disorder, first-episode depression, drug-naive patients, resting-state functional connectivity, brain network topology, small-world networks, global efficiency, path length, node centrality, caudate nucleus, hippocampus, default mode network
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Brain, Brain Mapping, Major Depressive Disorder, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Nerve Net, Neural Pathways, Oxygen, Statistics as Topic, Area Under Curve, Young Adult
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