Journal Article

FZJ-2026-01132

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Episode-specific cortical functional connectome reorganization and neurobiological correlates in bipolar disorder: a cross-sectional study

Liu, X. ; Wan, B.FZJ* ; Zhang, X.-H. ; Cui, R. ; Long, S. ; Ge, R. ; Liu, L. ; Xiao, J. ; Liu, Z.-Q. ; Yan, J. ; Xie, K. ; Yao, M. ; Wen, X.FZJ* ; Wang, S. ; Gao, Y. (Corresponding author)

2025
BioMed Central London

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Please use a persistent id in citations: doi:10.1186/s12916-025-04277-7  doi:10.34734/FZJ-2026-01132

Abstract: Background Bipolar disorder (BD) is a heterogeneous psychiatric condition characterized by distinct episodes: manic(BipM), depressive (BipD), mixed (mBD), and remission (rBD). Current evidence indicates alterations in brain functionalconnectivity in BD, yet a comprehensive understanding across all episodes remains incomplete.Methods Here, to investigate how different BD episodes alter brain functional organization, we calculated the sen‑sory‑association axis using diffusion map embedding on the functional connectome matrix and compared this axisbetween the four BD groups and neurotypical controls. Then, we employed regression dynamic causal modelingto investigate the directional information flow along the reorganized sensory‑association axis across different BDepisodes. Furthermore, we applied Nested Spectral Partitioning to decode functional integration and segregationalong the same axis. Finally, we compared the reorganization patterns with normative maps of clinical symptomatol‑ogy, cellular composition, and receptor distribution to elucidate symptom‑related and molecular‑level associations.Results Compared to healthy controls, we observed sensory region expansion and association region compressionin BipM, BipD, and rBD. The mBD showed expanded visual and prefrontal regions but compressed motor and pre‑cuneus regions. Analyzing neural information flow revealed reduced connectivity in association regions for BipMand BipD, indicating association dominance in functional reorganization. Conversely, mBD exhibited heightenedbidirectional signal flow between sensory and association regions, emphasizing increased integrative process‑ing. Network analyses further revealed increased integration and decreased segregation across unipolar episodes,with the highest integration in mBD. Clinical correlations highlighted that emotional fluctuations primarily relatedto association region reorganization, suggesting potential biomarkers for mood episode detection. Moreover, thesefunctional reorganizations spatially correlated with serotonin transporter, gamma‑aminobutyric acid type A recep‑tor, alpha‑4‑beta‑4 nicotinic acetylcholine receptor, and specific cortical neuron layers (layer 4 and layer 5 excitatoryneurons).

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Contributing Institute(s):

1. Gehirn & Verhalten (INM-7)

Research Program(s):

1. 5252 - Brain Dysfunction and Plasticity (POF4-525) (POF4-525)

Appears in the scientific report 2025; 2025

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