Abstract
OBJECTIVE: Adolescents and adults with bipolar disorder (BD) show white matter (WM) microstructural alterations in tracts important for emotion regulation and cognition, including the anterior corpus callosum, cingulum, and uncinate fasciculus. Less is known about WM microstructure in middle age and older adults with BD (MOABD), although they often have substantial mood symptoms, cognitive impairments, and suicide and dementia risk. The present study investigated WM microstructure in MOABD and its relationship with age. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: In a 2-site diffusion tensor imaging study of adults ages 40-79 years (primary sample: n = 88 MOABD, 93 age-comparable non-psychiatric adults (NP); confirmatory sample: n = 29 MOABD, 47 NP). WM fractional anisotropy (FA) in the corpus callosum, cingulum, and uncinate fasciculus were compared between groups. Furthermore, diagnosis by age interaction analysis was performed. RESULTS: Across both sites, relative to NP, MOABD showed significantly lower FA throughout corpus callosum and in left cingulum (p < 0.05, multiple comparisons-corrected). Lower FA in the bilateral uncinate was observed, significant at the primary site and with a similar effect size at the confirmatory site. Diagnosis by age interactions were not significant. CONCLUSIONS: The results support abnormalities in inter- and intra-hemispheric WM tracts connecting regions that subserve emotion regulation and cognition in MOABD, consistent with findings in younger cohorts with BD. Findings in the posterior corpus callosum suggest a greater extent of alterations in MOABD that may contribute to their phenotype, while findings in other regions align with prior research suggesting early WM neurodevelopmental alterations that persist into older adulthood.