Cortical Thickness in Middle and Older Aged Adults With Bipolar Disorder Across Six International Sites

08/08/2026

AI Summary

Adults with bipolar disorder showed significantly lower cortical thickness in ventral and dorsal prefrontal cortices and widespread regions compared with controls.
Cortical thinning correlated with increasing ageing across groups; deficits in ventral prefrontal cortex appear to persist from younger age.
Lithium treatment associated with greater frontal pole and anterior cingulate thickness, suggesting potential neuroprotective effects against cortical thinning.

AI Summary

RESULTS: Cortical thickness was significantly lower among BD in VPFC and DPFC, and additional distributed regions (pFDR < 0.05) and negatively associated with age (p < 0.05); group and age did not interact significantly.

CONCLUSIONS: In this international middle and older aged adult BD sample, lower VPFC cortical thickness was observed, suggesting these deficits persist from younger age.

Basic summary

Bipolar Disord. 2026 Sep;28(6):e70166. doi: 10.1111/bdi.70166.

ABSTRACT

BACKGROUND: Older adults with bipolar disorder (BD) are at high risk for severe mood symptoms, cognitive difficulties, and early mortality; however, underlying brain alterations have received little study. Gray matter decreases in ventral prefrontal cortex (VPFC) seen in younger persons with BD, and additionally in dorsal PFC (DPFC), are implicated. Here, cortical thickness was examined in an international sample.

METHODS: Cortical thickness in 34 regions was measured from structural magnetic resonance imaging data using enhancing neuroImaging genetics through meta-analysis pipelines for individuals with BD (n = 308) and non-psychiatric comparison participants (n = 287), ages 40-70y, from six Global Aging and Geriatric Experiments in BD (GAGE-BD) consortium sites. Group differences were assessed for VPFC, DPFC and remaining cortical regions, covarying for scanner, age and sex. Results were considered significant corrected for false discovery fate (FDR) at p_FDR < 0.05. Relationships with demographic and clinical factors were explored.

RESULTS: Cortical thickness was significantly lower among BD in VPFC and DPFC, and additional distributed regions (p_FDR < 0.05) and negatively associated with age (p < 0.05); group and age did not interact significantly. Relationships with BD subtype and medications were observed; lithium was associated with higher frontal pole and anterior cingulate thickness (p_FDR < 0.05).

CONCLUSIONS: In this international middle and older aged adult BD sample, lower VPFC cortical thickness was observed, suggesting these deficits persist from younger age. DPFC and additional regions of reduced cortical thickness could contribute to the older adult BD phenotype. Cortical thinning was more pronounced among older individuals regardless of diagnosis. Lithium may lessen cortical thinning.

PMID:42568249 | DOI:10.1111/bdi.70166

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