Widespread white matter tract aberrations in youth with familial risk for bipolar disorder

Abstract

Few studies have examined multiple measures of white matter (WM) differences in youth with familial risk for bipolar disorder (FR-BD). To investigate WM in the FR-BD group, we used three measures of WM structure and two methods of analysis. We used fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) to analyze diffusion tensor imaging (DTI) findings in 25 youth with familial risk for bipolar disorder, defined as having both a parent with BD and mood dysregulation, and 16 sex-, age-, and IQ-matched healthy controls. We conducted a whole brain voxelwise analysis using tract based spatial statistics (TBSS). Subsequently, we conducted a complementary atlas-based, region-of-interest analysis using Diffeomap to confirm results seen in TBSS. When TBSS was used, significant widespread between-group differences were found showing increased FA, increased AD, and decreased RD in the FR-BD group in the bilateral uncinate fasciculus, cingulum, cingulate, superior fronto-occipital fasciculus (SFOF), superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus, and corpus callosum. Atlas-based analysis confirmed significant between-group differences, with increased FA and decreased RD in the FR-BD group in the SLF, cingulum, and SFOF. We found significant widespread WM tract aberrations in youth with familial risk for BD using two complementary methods of DTI analysis.

784. Structural Dysconnectivity of Key Cognitive and Emotional Hubs in Young People at High Genetic Risk for Bipolar Disorder

“…Again, these regions reiterate those previously identified as having both altered fractional anisotropy 24,80 and decreased radial diffusivity 20 in HR individuals. The presence of this sub-network of stronger connections could thus be a compensatory response to the weaker sub-networks elsewhere in our HR cohort, preserving adaptive emotional regulation.…”

A voxel‐based diffusion tensor imaging study in unipolar and bipolar depression

“…Some studies suggest that the decrease in FA correlates with clinical markers such as the number of depressive episodes, time since onset of disease or severity of illness, which would point towards an effect of disease on the brain. However, other studies have indicated that there may be genetic influences on FA in these patients and groups at risk, which would suggest that FA reductions may be a trait and vulnerability marker of BD …”

“…However, other studies have indicated that there may be genetic influences on FA in these patients and groups at risk, which would suggest that FA reductions may be a trait and vulnerability marker of BD. 19,20 Hence, the main aim of the present study was to examine FA differences between BD and UD in well-characterized patient samples with a sample size more than a double those of the presently available reports. To address differences in the regional foci investigated in previous DTI studies on affective disorders, we used a comparable approach, reporting results of an analysis restricted to white matter only, and restricted to a priori tracts of interests.…”

Diffusion tensor imaging tractography study in bipolar disorder patients compared to first‐degree relatives and healthy controls

“…11 FA values were significantly decreased in BD patients compared to HC in the corpus callosum, [12][13][14][15][16] cingulum, [12][13][14]17 arcuate fasciculus, 12 superior longitudinal fasciculus, 17 uncinate fasciculus, [18][19][20] thalamic association fibers, 15,19,20 and the anterior limb of the internal capsule. 18,20,21 A few studies have reported increased FA in the uncinate fasciculus, 22 cingulum, 23 superior longitudinal fasciculus, 24 inferior longitudinal fasciculus, 24 corpus callosum, 25 and the occipital region. 25 Such variation could be partly explained by the heterogeneity of the study sample, differences in DTI technique, or data-acquisition methods.…”