Reduced white matter integrity and verbal fluency impairment in young adults with bipolar disorder: A diffusion tensor imaging study

Background: Clinical evidence shows that bipolar disorder (BD) is characterized by white matter (WM) microstructural abnormalities. However, little is known about the biological mechanisms associated with these abnormalities and their relationship with cognitive functioning. Methods: 49 adult BD patients ((M ± SD): 29.27±7.92 years; 17 males, 32 females; 34 BD-I, 10 BD-II, and 5 BD-NOS) and 28 age-matched normal subjects ((M ± SD): 29.19±7.35 years; 10 males and 18 females) underwent diffusion tensor imaging (DTI) imaging. DTI metrics were computed using whole-brain tract-based spatial statistics (TBSS) as part of the FMRIB Software Library. Measures of WM coherence (fractional anisotropy - FA) and axonal structure (mean, axial and radial diffusivity - MD, AD and RD) were employed to characterize the microstructural alterations in the limbic, commissural, association and projection fiber tracts. All participants performed the Brief Assessment of Cognition for Affective disorders (BAC-A). Results: BD patients performed poorly on verbal fluency tasks and exhibited large clusters of altered FA, RD and MD values within the retrolenticular part of the internal capsule, the superior and anterior corona radiata, and the corpus callosum. Increased FA values in the left IFOF and the forceps minor correlated positively with verbal fluency scores. Altered RD parameters in the corticospinal tract and the forceps minor were associated with reduced visuomotor abilities. Conclusions: The reported verbal fluency deficits and FA, RD and MD alterations in WM structures are potential cognitive and neural markers of BD. Abnormal RD values may be associated with progressive demyelination.