Steeper Slope of Age-Related Changes in White Matter Microstructure and Processing Speed in Bipolar Disorder

Abstract

Objectives Bipolar disorder (BD) is associated with compromised white matter (WM) integrity and deficits in processing speed (PS). However, few studies have investigated age relationships with WM structure and cognition to understand possible changes in brain health over the lifespan. This investigation explored whether BD and healthy comparison (HC) participants exhibited differential age-related associations with WM and cognition, which may be suggestive of accelerated brain and cognitive aging. Design Cross-sectional study. Setting University of California San Diego and the Veterans Administration San Diego Healthcare System. Participants 33 euthymic BD and 38 HC participants. Measurements Diffusion tensor imaging was acquired as a measure of WM integrity, and tract-specific fractional anisotropy (FA) was extracted utilizing the Johns Hopkins University probability atlas. PS was assessed with the Number and Letter Sequencing conditions of the Delis-Kaplan Executive Function System Trail Making Test. Results BD participants demonstrated slower PS compared to the HC group, but no group differences were found in FA across tracts. Multiple linear regressions revealed a significant group-by-age interaction for the right uncinate fasciculus, the left hippocampal portion of the cingulum and for PS, such that older age was associated with lower FA values and slower PS in the BD group only. The relationship between age and PS did not significantly change after accounting for uncinate FA, suggesting that the observed age associations occur independently. Conclusions Results provide support toward future study of the accelerated aging hypothesis by identifying markers of brain health that demonstrate a differential age association in BD.

White matter microstructure in youth with and at risk for bipolar disorder

“…This interpretation is consistent with the literature that comprises reports of reduced FA in the CST in individuals with or at risk for BD and in individuals with ADHD . The CST is a major motor pathway, and its microstructure has been positively associated with processing speed . Thus, altered WM microstructure in the CST might contribute to both reduced processing speed in BD.…”

“…44 The CST is a major motor pathway, and its microstructure has been positively associated with processing speed. 45 Thus, altered WM microstructure in the CST might contribute to both reduced processing speed 46 in BD.…”

Deficits of white matter axial diffusivity in bipolar disorder relative to major depressive disorder: No relationship to cerebral perfusion or body mass index

“…Consistent with this interpretation, a number of studies have reported genes to be associated with WMI deficits in BD, including ANK3 and HTLPR . Other studies in BD have found a negative association between length of illness and WMI . We found a trend correlation between the mean AD and duration of illness, but no association with age of onset.…”

Accelerated epigenetic aging and mitochondrial DNA copy number in bipolar disorder

“…Accelerated aging is commonly observed in several chronic illnesses, increasing the rate of aging-related medical conditions and shortening the life span in patients 1 – 4 . In particular, bipolar disorder (BD), an often severe and highly disabling psychiatric condition that affects around 1% of the population 5 , has been characterized by many features of aging that can complicate disease outcomes and converge to premature aging (commonly described as “accelerated aging” in the field) 6 , 7 .…”