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Journal Article Ahead of print 1 citation

PubMed: 42537498 DOI: 10.1016/j.nicl.2026.104045

The impact of functional architecture dynamics in bipolar disorder staging.

Neuroimage Clin 51:104045

Authors: Andrea Caporali, Francesca Martella, Salvatore Saluzzi, Nicolaja Girone, Beatrice Feliciani, Clara Cavallotto, Mauro Pettorruso, Simonetta Gerevini, Emi Bondi, Cristiana Perrotta, Mauro Gianni Perrucci, Giovanni Martinotti, Bernardo Dell'Osso, Annabella Di Giorgio, Claudio D'Addario, Francesco de Pasquale

Affiliations

  • Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy; School of Advanced Studies, Center for Neuroscience, University of Camerino, Camerino, Italy.
  • Department of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Teramo, Italy.
  • Department of Mental Health and Addictions, ASST Papa Giovanni XXIII, Bergamo, Italy.
  • Department of Mental Health, Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy.
  • Department of Neuroscience, Imaging and Clinical Sciences, University G. D'Annunzio Chieti-Pescara, Italy.
  • Neuroradiology Unit, ASST Papa Giovanni XXIII, Bergamo, Italy.
  • Department of Neuroscience, Imaging and Clinical Sciences, University G. D'Annunzio Chieti-Pescara, Italy; Institute for Advanced Biomedical Technologies (ITAB), University G. D'Annunzio Chieti-Pescara, Italy; UdA-TechLab, Research Center, University G. D'Annunzio Chieti-Pescara, Italy.
  • Department of Mental Health, Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy; CRC "Aldo Ravelli" for Neurotechnology and Experimental Brain Therapeutics, University of Milan, Milan, Italy; Department of Psychiatry and Behavioural Sciences, Stanford University, Stanford, CA, USA.
  • Department of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Teramo, Italy; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
  • Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy; IRCCS Santa Lucia Foundation, Rome, Italy.

Abstract

Bipolar disorder (BD) follows a neuro-progressive trajectory, yet current clinical staging models lack robust biological markers. Based on recent evidence, we hypothesized that BD stages are associated with alterations in the functional architecture of the Triple Network Model. We analyzed resting-state fMRI data from 123 individuals spanning five clinically defined BD stages. Using a hierarchical approach, we investigated how functional connectivity features characterize these stages, transitioning from coarse- to fine-grained analyses in both clinical classification (binary early-versus-late grouping to five-stage discrimination) and connectivity metrics (mean and standard deviation of connectivity to topological dynamic features). First, low-level functional connectivity features, combined with gene expression data, discriminated early- from late-stage illness, reaching higher performance than unimodal approaches. Next, evaluating the full staging spectrum revealed a non-linear trajectory in whole-brain connection density, which was lower at each successive stage from 0 to 3 but unexpectedly higher at stage 4. Network topology analysis contextualized this finding, revealing a reorganization of functional hubs in the final stage. Specifically, three hubs within the Salience Network exhibited decreased centrality despite the overall increase in connection density. This shift corresponded to a loss of temporal synchronization between these hubs and default-mode hubs, an axis of communication mediated by the salience network that is known to be important in healthy subjects and disrupted in psychiatric disorders. Overall, our findings suggest that late-stage BD is characterized by a subtle but significant reorganization of brain architecture, accompanied by alterations in the dynamics of the salience network which loses its coordinating role.

MeSH

Bipolar Disorder, Brain