White matter alterations in antipsychotic- and mood stabilizer-naïve individuals with bipolar II/NOS disorder

Abstract

Structural magnetic resonance imaging (MRI) studies using voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) have been inconsistent in demonstrating impairments in gray matter (GM) and white matter (WM) structures in bipolar disorder (BD). This may be a consequence of significant confounding effects of medication, illness history and selection of controls in existing studies. Study of bipolar II or not-otherwise-specified (BD II/NOS) disorder provides a solution to these confounds and a bridge to unipolar cases across the affective spectrum.Thirty-eight euthymic, antipsychotic- and mood stabilizer-naïve young adults (mean age = 20.9 years) with BD II/NOS and 37 age-, cognitive ability- and gender-matched healthy controls (HCs) underwent MRI. Voxel-wise and regional gray matter volume comparisons were conducted using voxel-based morphometry (VBM). Tract-based spatial statistics (TBSS) were used to assess whole-brain WM, as indexed using fractional anisotropy (FA), mean diffusivity (MD), parallel and perpendicular diffusion values. No between-group differences were observed for whole-brain VBM comparisons. By contrast, in comparison to HCs, participants with BD II/NOS had significant widespread reductions in FA and increased MD and perpendicular diffusion values in virtually all the major cortical white matter tracts.These data suggest pathophysiological involvement of WM microstructures – but not GM macrostructures – in high functioning BD II/NOS patients at an early age and before significant clinical adversity has been recorded. We propose that white matter development is a valid candidate target for understanding genetic and environmental antecedents to bipolar disorder and mood disorder more generally.

White matter microstructure in youth with and at risk for bipolar disorder

“…In REL, but not BD youth, the findings in the CST were more pronounced in the subgroup with a diagnosis of ADHD, which suggests that abnormalities in this tract might not be specific to BD. This interpretation is consistent with the literature that comprises reports of reduced FA in the CST in individuals with or at risk for BD and in individuals with ADHD . The CST is a major motor pathway, and its microstructure has been positively associated with processing speed .…”

“…13 ). Of note, 12 studies were conducted in pediatric BD and, as in adult BD, reduced FA in the anterior CC, cingulum bundle, UNC, SLF, CST and ATR, 14 emerged as the most robust findings. Moreover, seven studies in unaffected adult REL reported reduced FA in the CC, 15 cingulum bundle, 16 SLF, 16,17 ATR, 15,17 and UNC.…”

The association of sleep and physical activity with integrity of white matter microstructure in bipolar disorder patients and healthy controls

“…A voxel-based meta-analysis of 18 DTI studies found that bipolar patients have lower FA in the genu of the corpus callosum and left cingulum white matter, suggesting poor integrity of white matter (Wise et al, 2016). This finding has also been established in antipsychotic and mood-stabilizer naïve patients (Yip et al, 2013). …”

Volumetric, cortical thickness and white matter integrity alterations in bipolar disorder type I and II

“…However, as BD is often difficult to diagnose, it is likely that documented time since diagnosis data would be inaccurate as patients are likely have developed BD years before a diagnosis was reached. We did not have details on the number of episodes, time spent in episodes, the number of hospitalizations, and the nature of the index episode at the time of imaging, all of which are important aspects of longitudinal severity of BD, which may confound the findings of this study (Yip et al, 2013). Although the patients differed in the types of medications they had been treated with, the sample sizes of each type of medication were not large enough for the impact upon volumetrics to investigated.…”