Longitudinal Diffusion Tensor Imaging Study of Adolescents and Young Adults With Bipolar Disorder

Abstract

Longitudinal neuroimaging during adolescence/young adulthood, when bipolar disorder (BD) commonly emerges, can help elucidate the neurodevelopmental pathophysiology of BD. Adults with BD have shown reduced structural integrity in the uncinate fasciculus (UF), a white matter (WM) tract providing major connections between the amygdala and ventral prefrontal cortex (vPFC), important in emotion regulation. In this longitudinal diffusion tensor imaging (DTI) study of adolescents/young adults, we hypothesized differences in age- and time-related changes in UF integrity in BD compared to healthy controls (HC). Two DTI scans were obtained in 27 adolescents/young adults with BD and 37 HC adolescents/young adults, on average approximately 2.5 years apart. Interactions between diagnosis with age and with time for UF fractional anisotropy (FA) were assessed. Exploratory analyses were performed including euthymic-only participants with BD, and for potential influences of demographic and clinical factors. Whole-brain analyses were performed to explore for interactions in other regions. There were significant interactions between diagnosis with age and with time for UF FA (p< .05). Healthy control adolescents/young adults showed significant UF FA increases with age and over time (p< .05), whereas no significant changes with age or over time were observed in the adolescents/young adults with BD. Significant interactions with age and time were also observed in analyses including euthymic-only participants with BD (p< .05). These findings provide neuroimaging evidence supporting differences in UF WM structural development during adolescence/young adulthood, suggesting that differences in the development of an amygdala-vPFC system subserving emotion regulation may be a trait feature of BD neurodevelopment.