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Lookup NU author(s): Dr Beth Little, Dr Peter GallagherORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Background: Cognitive impairment across cognitive domains and brain structure alterations are well documented in persons with bipolar disorder (BD) but the association between them is still unclear. Previous studies have generally applied univariate models to investigate brain-cognition correlations, which limits the discovery of complex association patterns. The aim of this study was to apply canonical correlation analysis (CCA) to identify multivariate associations between brain structure and cognitive impairment in BD. Methods: Cognitively impaired persons with BD (n = 169) in full or partial remission were included from four prior pro-cognitive intervention studies. We included healthy controls (HC, n = 40) for the calculation of covariate-adjusted brain and cognition z-scores. All participants underwent structural magnetic resonance imaging and an extensive cognitive test battery. We conducted principal component analysis on the brain data within the BD group to reduce the number of variables in the dataset. We then applied CCA to investigate multivariate associations between brain structure and cognition in the BD cohort. Results: Poorer performance across working memory, psychomotor speed, executive functions, and verbal learning and memory correlated with lower grey matter volume in frontotemporal regions, the right hippocampus, and the left caudate nucleus, and with larger frontotemporal and right posterior cingulate gyral thickness. Conclusions: The association between cognition, reduced grey matter volume and larger thickness in frontotemporal and posterior cingulate regions suggests that cognitive impairment originates from dysregulated, rather than simply reduced, neuroplasticity processes. Aberrant volume and thickness measures in these regions are potential treatment targets to promote cognition in BD.
Author(s): Schandorff JM, Madsen ABF, Damgaard V, Little B, Sankar A, Macoveanu J, Frokjaer VG, Kessing LV, Jørgensen MB, Knudsen GM, Gallagher P, Miskowiak KW
Publication type: Article
Publication status: Published
Journal: Progress in Neuro-Psychopharmacology and Biological Psychiatry
Year: 2025
Volume: 140
Print publication date: 13/07/2025
Online publication date: 10/06/2025
Acceptance date: 08/06/2025
Date deposited: 18/06/2025
ISSN (print): 0278-5846
ISSN (electronic): 1878-4216
Publisher: Elsevier Inc.
URL: https://doi.org/10.1016/j.pnpbp.2025.111425
DOI: 10.1016/j.pnpbp.2025.111425
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