Protocol for a systematic review and meta-analysis of coordinate-based network mapping of brain structure in bipolar disorder across the lifespan

Journal article

Bipolar disorder (BD) is increasingly recognized not just for its characteristic mood fluctuations but also for persistent cognitive impairments that can profoundly affect daily functioning. This thesis investigates the interplay between neurocognitive deficits, brain structure, and the aging process in BD, drawing on three complementary lines of research. Study 1 cross-sectionally examines cognitive trajectories across younger and older adults with BD. Results suggest that certain cognitive domains (executive function and processing speed) demonstrate “accelerated aging,” whereas verbal memory shows an early onset of impairment without significant progression. Visuospatial memory and reasoning skills largely follow normal aging patterns, indicating that BD-related cognitive decline is domain-specific. Study 2 synthesizes data from 80 neuroimaging studies in BD through a systematic review and meta-analysis. Results suggest moderate yet heterogeneous associations between structural brain measures and cognition in BD. Clinical moderators—such as mood state and BD subtype—significantly influenced observed effect sizes, highlighting the importance of refined clinical phenotyping. Notably, the review finds that variability in cognitive domains, rather than specific brain networks, drives the largest source of heterogeneity, suggesting that domain-specific vulnerabilities may be a unifying theme in BD-related cognitive associations. Study 3 employs a multivariate partial least squares (PLS) approach to link structural imaging measures—grey matter (cortical thickness, subcortical volumes) and white matter (fractional anisotropy)—to cognition in BD. Brain structure acted as a partial mediator of these brain–cognition associations in BD, contrasting with healthy controls, where it did not. Furthermore, white matter integrity is more globally predictive of cognitive function in BD, reinforcing a neuroprogressive model in which repeated mood episodes and other illness-related stressors compound typical age-related deterioration. Taken together, these findings support the view that BD involves domain-specific and global cognitive deficits shaped by both normal aging processes and illness-specific neuroprogression. There is a need for clinical trials of targeted interventions early in the course of illness employing multimodal neuroimaging and refined clinical stratification. This approach could identify interventions that preserve cognition and improve long-term outcomes for individuals with BD.Ph.D

Authors: Jones, BDM; Zhukovsky, P; Hawco, C; Ortiz, A; Cipriani, A

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Cambridge University Press
• Journal: BJPsych Open
• Volume: 9
• Issue: 6
• Pages: e178-e178
• Article number: e178
• Publication date: 2023-10-09
• DOI: 10.1192/bjo.2023.569
• EISSN: 2056-4724
• ISSN: 2056-4724
• Language: English
• Keywords: Biology; Cognition; Clinical psychology; Psychology; Pathology; Medicine; Meta-analysis; Psychiatry; MEDLINE; Neuroscience; Bipolar disorder; PsycINFO; Neuroimaging; Brain mapping