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Associations between structural brain measures and cognitive function in bipolar disorder: a systematic review and meta-analysis

Neuropsychopharmacology volume 50, pages 1256–1264 (2025)Cite this article

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Abstract

Bipolar disorder (BD) is a chronic condition characterized by recurrent mood episodes and persistent cognitive deficits that span multiple domains, ultimately impacting daily functioning. Understanding the neural underpinnings of these impairments is crucial. In a systematic review and meta-analysis examining 80 studies (with 50 meeting criteria for meta-analysis) of adults with BD, relationships between structural brain measures and cognitive performance were evaluated. Participants were diagnosed according to standard criteria, underwent structural and diffusion-weighted MRI, and completed standardized cognitive assessments. The meta-analyses indicated significant associations between both grey matter and white matter indices and cognitive functioning, reflected in moderate effect sizes. Notably, these associations exhibited substantial heterogeneity. Meta-regression revealed that bipolar subtype and current mood state moderated the observed brain-cognition relationships, with bipolar I and euthymic individuals showing higher associations with grey matter metrics. Cognitive domain differences also played a key role, indicating that certain cognitive functions are more strongly linked to structural brain measures than others. Brain networks emerged as a global influence on cognition, with limited differences in pairwise comparisons. Age, sex, psychosis, and mania were not found to significantly moderate these relationships. Overall, this work suggests that structural alterations in grey and white matter in individuals with BD may contribute meaningfully to cognitive difficulties, while brain networks may provide a broad integrative framework for these associations. These findings underscore the importance of considering both global and specific neural factors when exploring the pathophysiology of cognitive impairment in BD.

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Fig. 1: Grey matter pooled Z scores - forest plot.
Fig. 2: White matter pooled Z scores - forest plot.
Fig. 3: Estimates cognitive domains and networks.
Fig. 4: Significant cognition network connections.

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Extracted data is included in the supplemental information.

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Funding

This work was supported by a CIHR Postdoctoral Fellowship to BDMJ.

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Authors and Affiliations

  1. University of Toronto, Department of Psychiatry, Toronto, ON, Canada

    Brett D. M. Jones, Julia Gallucci, Peter Zhukovsky, Stanley Wong, Aristotle N. Voineskos, Colin Hawco, Abigail Ortiz, Benoit H. Mulsant & M. Ishrat Husain

  2. Centre for Addiction and Mental Health, Toronto, ON, Canada

    Brett D. M. Jones, Julia Gallucci, Peter Zhukovsky, Stanley Wong, Aristotle N. Voineskos, Colin Hawco, Abigail Ortiz, Benoit H. Mulsant & M. Ishrat Husain

  3. Princess Margaret Cancer Centre, Toronto, ON, Canada

    On Yee Jones

  4. Queen’s University, Kingston, ON, Canada

    Karina Lakhani & Rayyan Farooqui

  5. McMaster University, Hamilton, ON, Canada

    Lauren Stirpe

  6. Western University, London, ON, Canada

    Ahmed K. Eltom Mohamed & Paramveer Love

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  1. Brett D. M. Jones
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All co-authors contributed to the conception of the work, drafting the work, and final approval of the version published.

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Correspondence to Brett D. M. Jones.

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Jones, B.D.M., Gallucci, J., Jones, O.Y. et al. Associations between structural brain measures and cognitive function in bipolar disorder: a systematic review and meta-analysis. Neuropsychopharmacol. 50, 1256–1264 (2025). https://doi.org/10.1038/s41386-025-02096-1

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