Right Orbitofrontal Corticolimbic and Left Corticocortical White Matter Connectivity Differentiate Bipolar and Unipolar Depression

Abstract

Objectives The absence of pathophysiologically relevant diagnostic markers of bipolar disorder (BD) leads to its frequent misdiagnosis as unipolar depression (UD). We aimed to determine whether whole brain white matter connectivity differentiated BD from UD depression. Methods We employed a three-way analysis of covariance, covarying for age, to examine whole brain fractional anisotropy (FA), and corresponding longitudinal and radial diffusivity, in currently depressed adults: 15 with BD-type I (mean age 36.3 years, SD 12.0 years), 16 with recurrent UD (mean age 32.3 years, SD 10.0 years), and 24 healthy control adults (HC) (mean age 29.5 years, SD 9.43 years). Depressed groups did not differ in depression severity, age of illness onset, and illness duration. Results There was a main effect of group in left superior and inferior longitudinal fasciculi (SLF and ILF) (all F ≥ 9.8; p ≤ .05, corrected). Whole brain post hoc analyses (all t ≥ 4.2; p ≤ .05, corrected) revealed decreased FA in left SLF in BD, versus UD adults in inferior temporal cortex and, versus HC, in primary sensory cortex (associated with increased radial and decreased longitudinal diffusivity, respectively); and decreased FA in left ILF in UD adults versus HC. A main effect of group in right uncinate fasciculus (in orbitofrontal cortex) just failed to meet significance in all participants but was present in women. Post hoc analyses revealed decreased right uncinate fasciculus FA in all and in women, BD versus HC. Conclusions White matter FA in left occipitotemporal and primary sensory regions supporting visuospatial and sensory processing differentiates BD from UD depression. Abnormally reduced FA in right fronto-temporal regions supporting mood regulation, might underlie predisposition to depression in BD. These measures might help differentiate pathophysiologic processes of BD versus UD depression.

Is depression a disconnection syndrome? Meta- analysis of diffusion tensor imaging studies in patients with MDD

“…For sensitivity testing, we excluded 3 articles that used TBSS analysis [20][21][22] and then reanalyzed using GingerALE software. The result was consistent with the original meta-analysis of all 11 articles.…”

Subcortical volumes differentiate Major Depressive Disorder, Bipolar Disorder, and remitted Major Depressive Disorder

“…The results of these studies indicate that, compared to MDD, BD is associated with greater deep white matter hyperintensities (Dupont et al, 1995;Silverstone et al, 2003), reduced fractional anisotropy of the left superior longitudinal fasciculus (Versace et al, 2010), decreased habenula volume (Savitz et al, 2011), reduced cortical thickness in caudal middle frontal cortex, inferior parietal cortex, and precuneus (Lan et al, 2014), and increased thalamic volume (Dupont et al, 1995). In addition, Redlich et al found clusters of reduced gray matter that spanned the hippocampal formation, amygdala, putamen, insula, and temporal pole in depressed BD compared to MDD individuals, and a cluster in anterior cingulate that was reduced in MDD compared to depressed BD individuals (Redlich et al, 2014).…”

Altered effective connectivity model in the default mode network between bipolar and unipolar depression based on resting-state fMRI

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