Disrupted white matter microstructure correlates with impulsivity in children and adolescents with bipolar disorder

Altered white matter (WM) microstructure likely occurs in children with bipolar disorder (BD) with impulsivity representing one of the core features. However, altered WM microstructures and their age-related trendlines in children with BD and those at high-risk of developing BD, as well as correlations of WM microstructures with impulsivity, have been poorly investigated. In this study, diffusion MRI, cognitive, and impulsivity assessments were obtained from children/adolescents diagnosed with BD, offspring of individuals with BD (high-risk BD) and age-matched healthy controls. A novel atlas-based WM skeleton measurement approach was used to quantify WM microstructural integrity with all diffusion-tensor-imaging (DTI) metrics including fractional anisotropy, axial, mean and radial diffusivity to survey entire WM tracts and ameliorate partial volume effects. Among all DTI-derived metric measures, radial diffusivity quantifying WM myelination was found significantly higher primarily in corpus callosum and in the corona radiata in children with BD compared to controls. Distinguished from age-related progressively decreasing diffusivities and increasing fractional anisotropy in healthy controls, flattened age-related trendlines were found in BD group, and intermediate developmental rates were observed in high-risk group. Larger radial diffusivity in the corpus callosum and corona radiata significantly correlated with shorter response times to affective words that indicate higher impulsivity in the BD group, whereas no such correlation was found in the healthy control group. This work corroborates the progressive nature of pediatric BD and suggests that WM microstructural disruption involved in affective regulation and sensitive to impulsivity may serve as a biomarker of pediatric BD progression.