Elevated Left and Reduced Right Orbitomedial Prefrontal Fractional Anisotropy in Adults With Bipolar Disorder Revealed by Tract-Based Spatial Statistics

Abstract

Context Diffusion tensor imaging (DTI) studies in adults with bipolar disorder (BD) indicate altered white matter (WM) in the orbitomedial prefrontal cortex (OMPFC), potentially underlying abnormal prefrontal corticolimbic connectivity and mood dysregulation in BD. Objective To use tract-based spatial statistics (TBSS) to examine WM skeleton (ie, the most compact whole-brain WM) in subjects with BD vs healthy control subjects. Design Cross-sectional, case-control, whole-brain DTI using TBSS. Setting University research institute. Participants Fifty-six individuals, 31 having a DSM-IV diagnosis of BD type I (mean age, 35.9 years [age range, 24-52 years]) and 25 controls (mean age, 29.5 years [age range, 19-52 years]). Main Outcome Measures Fractional anisotropy (FA) longitudinal and radial diffusivities in subjects with BD vs controls (covarying for age) and their relationships with clinical and demographic variables. Results Subjects with BD vs controls had significantly greater FA (t>3.0, P≤.05 corrected) in the left uncinate fasciculus (reduced radial diffusivity distally and increased longitudinal diffusivity centrally), left optic radiation (increased longitudinal diffusivity), and right anterothalamic radiation (no significant diffusivity change). Subjects with BD vs controls had significantly reduced FA (t>3.0, P≤.05 corrected) in the right uncinate fasciculus (greater radial diffusivity). Among subjects with BD, significant negative correlations (P<.01) were found between age and FA in bilateral uncinate fasciculi and in the right anterothalamic radiation, as well as between medication load and FA in the left optic radiation. Decreased FA (P<.01) was observed in the left optic radiation and in the right anterothalamic radiation among subjects with BD taking vs those not taking mood stabilizers, as well as in the left optic radiation among depressed vs remitted subjects with BD. Subjects having BD with vs without lifetime alcohol or other drug abuse had significantly decreased FA in the left uncinate fasciculus. Conclusions To our knowledge, this is the first study to use TBSS to examine WM in subjects with BD. Subjects with BD vs controls showed greater WM FA in the left OMPFC that diminished with age and with alcohol or other drug abuse, as well as reduced WM FA in the right OMPFC. Mood stabilizers and depressed episode reduced WM FA in left-sided sensory visual processing regions among subjects with BD. Abnormal right vs left asymmetry in FA in OMPFC WM among subjects with BD, likely reflecting increased proportions of left-sided longitudinally aligned and right-sided obliquely aligned myelinated fibers, may represent a biologic mechanism for mood dysregulation in BD.

Quantitative Tract-Specific Measures of Uncinate and Cingulum in Major Depression Using Diffusion Tensor Imaging

“…Compared with HC subjects, patients with anxiety disorder had significantly lower FA localized to the right UF white matter near the orbitofrontal cortex (Phan et al, 2009). Likewise, patients with bipolar disorder showed similar abnormalities in the UF (McIntosh et al, 2008;Versace et al, 2008;Versace et al, 2010). Although we did not find abnormalities in the left UF in our depressed subjects, a previous study demonstrated that bipolar patients exhibited divergent FA changes in the left vs the right UF (greater FA in the left UF and lower FA in the right UF) (Versace et al, 2008).…”

“…As previously mentioned in the Introduction section, these regions have been previously investigated and shown to be altered in several imaging studies on mood disorders. For example, decreased radial diffusivity in the orbitomedial prefrontal cortex was reported in bipolar subjects relative to HC (Versace et al, 2008) and decreased FA in the anterior cingulate cortex was reported in subjects with acute coronary syndrome who developed persistent depression (Rapp et al, 2010). However, further studies are needed to directly examine which specific regions contribute to the FA reduction in the right UF.…”

“…In contrast, Taylor et al (2007) found early-onset geriatric depressed subjects exhibited lower FA of the left UF compared with mid and late onset or HC subjects. Furthermore, converging lines of evidence implicated the possible involvement of UF in other neuropsychiatric illnesses that often overlap with MDD including anxiety disorders (Phan et al, 2009) and bipolar affective disorder (McIntosh et al, 2008;Versace et al, 2008). Compared with HC subjects, patients with anxiety disorder had significantly lower FA localized to the right UF white matter near the orbitofrontal cortex (Phan et al, 2009).…”

Predicting White Matter Integrity from Multiple Common Genetic Variants

“…These studies show the utility of DTI in neuropsychiatric research. In several studies, treatment of neuropsychiatric patients has also been associated with changes in DTI measures (Versace et al, 2008;Yoo et al, 2007). This also shows the promise of DTI for understanding therapeutic effects.…”

Diffusion magnetic resonance imaging for Brainnetome: A critical review

“…In addition, when examination is confined to a specific sub-network (as detailed in the following section), localized fiber tracts can be selected by the ROIs, such as anterior cingulate cortex [75,76] , prefrontal cortex [77] , and motor areas [78] . We can also leverage fiber clustering methods [79,80] , or mutually combine with fMRI [81,82] to group fiber tracts that predict different connectivity paths.…”