Age‐associated alterations in corpus callosum white matter integrity in bipolar disorder assessed using probabilistic tractography

Abstract

Objectives Atypical age-associated changes in white matter integrity may play a role in the neurobiology of bipolar disorder, but no studies have examined the major white matter tracts using nonlinear statistical modeling across a wide age range in this disorder. The goal of this study was to identify possible deviations in the typical pattern of age-associated changes in white matter integrity in patients with bipolar disorder across the age range of 9 to 62 years. Methods Diffusion tensor imaging was performed in 57 (20M/37F) patients with a diagnosis of bipolar disorder and 57 (20M/37F) age- and sex-matched healthy volunteers. Mean diffusivity and fractional anisotropy were computed for the genu and splenium of the corpus callosum, two projection tracts, and five association tracts using probabilistic tractography. Results Overall, patients had lower fractional anisotropy and higher mean diffusivity compared to healthy volunteers across all tracts (while controlling for the effects of age and age2). In addition, there were greater age-associated increases in mean diffusivity in patients compared to healthy volunteers within the genu and splenium of the corpus callosum beginning in the second and third decades of life. Conclusions Our findings provide evidence for alterations in the typical pattern of white matter development in patients with bipolar disorder compared to healthy volunteers. Changes in white matter development within the corpus callosum may lead to altered inter-hemispheric communication that is considered integral to the neurobiology of the disorder.

White matter abnormalities in the fornix are linked to cognitive performance in SZ but not in BD disorder: An exploratory analysis with DTI deterministic tractography

“…However, none of the aforementioned studies employed deterministic tractography. Indeed, regardless the limited evidence of tractography, the few existing studies support our findings (Emsell et al, 2013;Sarrazin et al, 2014;Toteja et al, 2014). However, technical limitations of previous DTI studies might account for the lack of evidence involving the fornix, as acknowledged by more recent investigations (Emsell et al, 2013).…”

“…However, the fornix WM microstructure has been less frequently examined. The existing results were controversial, showing no major structural changes in this region in BD (al., 2008;Barysheva et al, 2013), but also FA changes in the fornix in BD ( Barnea-Goraly et al, 2009;Oertel-Knochel et al, 2014). However, none of the aforementioned studies employed deterministic tractography.…”

“…One tractography investigation observed lower FA and higher mean diffusivity (MD) in the corpus callosum (CC) (i.e., genu, splenium) and also in both projection and association fibers. MD changes were associated with age in the genu and splenium of the corpus callosum (Toteja et al, 2014). In another study, decreased FA in the anterior thalamic radiation and uncinate fasciculus were reported (Lin and al, 2010).…”

“…In fact, while most investigations have reported fractional anisotropy (FA) reductions (Benedetti et al, 2011a;Chaddock et al, 2009;Lu et al, 2011;Macritchie et al, 2010) a smaller amount of studies have noted FA increases compared to healthy controls (Versace et al, 2008;Wessa et al, 2009). To the best of our knowledge, there are scarce studies carried out with DTI tractography in BD samples (Barysheva et al, 2013;Emsell et al, 2013;Lin and al, 2010;Sarrazin et al, 2014;Toteja et al, 2014). One tractography investigation observed lower FA and higher mean diffusivity (MD) in the corpus callosum (CC) (i.e., genu, splenium) and also in both projection and association fibers.…”

Steeper Slope of Age-Related Changes in White Matter Microstructure and Processing Speed in Bipolar Disorder

“…One recent cross-sectional study, using probabilistic tractography, reported a stronger negative association between age and WM integrity in the corpus callosum of BD patients than HCs (11). However, other studies have found no evidence of differential age associations with WM integrity (12), though small sample sizes and short follow-up periods may have limited the statistical power.…”