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

Abstract

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.

Stay connected

“…These results seem to support both models, suggesting that the cerebral alterations in psychosis involve an on-going process of genetic and environmental as well as epistatic and epigenetic interactions 37,42 , but also illness-or treatment related factors. As stated before, multiple brain areas have been associated with schizophrenia, pointing to altered networks / neuronal connectivity, as demonstrated in several neurophysiological and functional imaging studies 43,44 . The dyscon-nectivity hypothesis as formulated by implies that the core pathology of schizophrenia is the result of faults in abnormal epigenetic, activity-and experience dependent N-methyl-D-aspartate receptor (NMDAR) mediated synaptic plasticity by modulatory neurotransmitters like dopamine.…”

“…Reduced longitudinal FA increase was found in adolescent cannabis users (n=23) in 5 clusters of fronto-parietal association fibers over a 2-year interval 42 , as well as a significant FA decrease over time in the left ILF in adolescents with cannabis use disorder (n=19), associated with more cannabis exposure, compared to healthy controls 43 . After an 18-month follow-up, poorer WM integrity was reported, although mainly predicted by alcohol, not marijuana in 7 fronto-parietal tracts in adolescent substance users (n=41) 36 .…”

“…These atlases differ considerably in the definitions of the boundaries of particular white matter tracts and of the labeling of certain brain regions, in an attempt to account for overlap and crossing fibers. We used two versions of the white matter JHU atlas 42,43 to include most major white matter tracts. The differences in atlases among the DTI studies hamper between-study comparisons.…”

“…Specifically, the left PTR and the right cingulum revealed a significant decrease of mean FA over time in siblings, whereas controls showed an increase. The PTR has previously been associated with schizophrenia 15,43 , e.g. with impaired emotional self-awareness 44 .…”

“…The Johns Hopkins University International Consortium for Brain Mapping (JHU ICBM)-DTI-81 white-matter atlas labels 42 were used to label significant voxels and assign a specific tract name. If the voxels did not match with the JHU ICBM labels, they were identified using the JHU white-matter tractography atlas 43 . A binary mask was created containing the significant clusters in order to extract FA values of the individual participants.…”