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Peer-reviewedCC BY 4.0Frontiers in Psychiatry

Neuroprogression of chronic stress-induced depression via longitudinal fMRI

  • Yu Yang1,2,3
  • Huixia Jia1,2,3
  • He Liu1,2,3
  1. 1Department of Systems Science, Faculty of Arts and Sciences, Beijing Normal University
  2. 2International Academic Center of Complex Systems, Beijing Normal University
  3. 3School of Systems Science, Beijing Normal University
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Abstract

Background: Depression is increasingly viewed as a progressive neurobiological trajectory, yet the spatiotemporal transition from early mood dysregulation to chronic network failure, and its relation to disease-related functional decline, remains unclear. Using a chronic unpredictable mild stress (CUMS) mouse model, we aimed to map the longitudinal brain transformation from local spontaneous activity to global network dysfunction via multi-parametric MRI.

Methods: Longitudinal functional magnetic resonance imaging (fMRI) was performed on a cohort of CUMS mice (n = 7) across three longitudinal time points: Day 0 (baseline), Day 5 CUMS, and Day 10 CUMS. We integrated four analytical approaches: fALFF, static functional connectivity, graph theory, and dFC/dALFF.

Results: Depression progression followed a hierarchical spatiotemporal dissolution. fALFF revealed sequential breakdown of local hubs in caudoputamen, medial prefrontal cortex, and hippocampus, suggesting involvement of motor-motivational and executive deficits. sFC showed sensory-limbic uncoupling between caudoputamen and visual areas, and altered mPFC-AON connectivity and hippocampal prefrontal (HPF-PL) dysconnectivity, indicating limbic-olfactory loop disruption. Graph theory indicated preserved global node efficiency but widespread loss of node local efficiency and clustering. Dynamic analyses uncovered a shift from flexible network reconfiguration to dynamic rigidity.

Conclusion: Longitudinal CUMS exposure was associated with progressive alterations in functional network organization. The prefrontal olfactory dysconnectivity and onset of dynamic rigidity represent candidate multi-scale and longitudinal imaging features that warrant future validation.

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Cite

BibTeXRIS
BibTeX
@article{yang2026neuroprogression,
  title = {{Neuroprogression of chronic stress-induced depression via longitudinal fMRI}},
  author = {Yu Yang and Huixia Jia and He Liu},
  journal = {Frontiers in Psychiatry},
  year = {2026},
  month = oct,
  doi = {10.3389/fpsyt.2026.1898694},
  url = {https://www.frontiersin.org/articles/10.3389/fpsyt.2026.1898694/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Neuroprogression of chronic stress-induced depression via longitudinal fMRI
AU  - Yu Yang
AU  - Huixia Jia
AU  - He Liu
PY  - 2026
DA  - 2026/10/14
JO  - Frontiers in Psychiatry
DO  - 10.3389/fpsyt.2026.1898694
UR  - https://www.frontiersin.org/articles/10.3389/fpsyt.2026.1898694/full
AB  - Background: Depression is increasingly viewed as a progressive neurobiological trajectory, yet the spatiotemporal transition from early mood dysregulation to chronic network failure, and its relation to disease-related functional decline, remains unclear. Using a chronic unpredictable mild stress (CUMS) mouse model, we aimed to map the longitudinal brain transformation from local spontaneous activity to global network dysfunction via multi-parametric MRI.  Methods: Longitudinal functional magnetic resonance imaging (fMRI) was performed on a cohort of CUMS mice (n = 7) across three longitudinal time points: Day 0 (baseline), Day 5 CUMS, and Day 10 CUMS. We integrated four analytical approaches: fALFF, static functional connectivity, graph theory, and dFC/dALFF.  Results: Depression progression followed a hierarchical spatiotemporal dissolution. fALFF revealed sequential breakdown of local hubs in caudoputamen, medial prefrontal cortex, and hippocampus, suggesting involvement of motor-motivational and executive deficits. sFC showed sensory-limbic uncoupling between caudoputamen and visual areas, and altered mPFC-AON connectivity and hippocampal prefrontal (HPF-PL) dysconnectivity, indicating limbic-olfactory loop disruption. Graph theory indicated preserved global node efficiency but widespread loss of node local efficiency and clustering. Dynamic analyses uncovered a shift from flexible network reconfiguration to dynamic rigidity.  Conclusion: Longitudinal CUMS exposure was associated with progressive alterations in functional network organization. The prefrontal olfactory dysconnectivity and onset of dynamic rigidity represent candidate multi-scale and longitudinal imaging features that warrant future validation.
SN  - 1664-0640
ER  -