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White matter abnormalities in adults with bipolar disorder type-II and unipolar depression.

ABSTRACT: Discerning distinct neurobiological characteristics of related mood disorders such as bipolar disorder type-II (BD-II) and unipolar depression (UD) is challenging due to overlapping symptoms and patterns of disruption in brain regions. More than 60% of individuals with UD experience subthreshold hypomanic symptoms such as elevated mood, irritability, and increased activity. Previous studies linked bipolar disorder to widespread white matter abnormalities. However, no published work has compared white matter microstructure in individuals with BD-II vs. UD vs. healthy controls (HC), or examined the relationship between spectrum (dimensional) measures of hypomania and white matter microstructure across those individuals. This study aimed to examine fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AD), and mean diffusivity (MD) across BD-II, UD, and HC groups in the white matter tracts identified by the XTRACT tool in FSL. Individuals with BD-II (n = 18), UD (n = 23), and HC (n = 24) underwent Diffusion Weighted Imaging. The categorical approach revealed decreased FA and increased RD in BD-II and UD vs. HC across multiple tracts. While BD-II had significantly lower FA and higher RD values than UD in the anterior part of the left arcuate fasciculus, UD had significantly lower FA and higher RD values than BD-II in the area of intersections between the right arcuate, inferior fronto-occipital and uncinate fasciculi and forceps minor. The dimensional approach revealed the depression-by-spectrum mania interaction effect on the FA, RD, and AD values in the area of intersection between the right posterior arcuate and middle longitudinal fasciculi. We propose that the white matter microstructure in these tracts reflects a unique pathophysiologic signature and compensatory mechanisms distinguishing BD-II from UD.

SUBMITTER: Manelis A

PROVIDER: S-EPMC8024340 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:It is unknown if young medication-naïve bipolar II (BPII) depressed patients have increased white matter (WM) disruptions. 27 each of young (average 23 years) and treatment-naïve BPII depressed, unipolar depressed (UD) patients and age-sex-education matched healthy controls (HC) underwent 3 T MRIs with diffusion tensor imaging. Diagnostic ratings included Structured Clinical Interview for DSM Disorders (SCID), Montgomery-Åsberg Depression Rating Scale (MADRS), Young Mania Rating Scale (YMRS) and Hamilton Anxiety Rating Scale (HAM-A). Patients were clinically depressed (MADRS-BPII: 26.15 [SD9.25], UD: 25.56 [5.24], p = 0.86). Compared to UD, BPII had increased family bipolarity (BPII 13.6% vs UD 2.5%, p = 0.01, φc = 0.28), hypomanic symptoms (YMRS-BPII: 4.22 [4.24], UD: 1.33 [2], p = 0.02, d = 0.87), lifetime number of depressive episodes (BPII: 2.37 [1.23], UD: 1.44 [0.75], p = 0.02, d = 0.91), lifetime and current-year number of episodes (lifetime BPII: 50.85 [95.47], UD: 1.7 [1.03]; current-year BPII: 9.93 [16.29], UD: 1.11 [0.32], ps = 0.04, ds = 0.73-0.77) and longer illness duration (BPII: 4.96 years [3.96], UD: 2.99 [3.33], p = 0.15, d = 0.54). BPII showed no increased WM disruptions vs UD or HC in any of the 15 a priori WM tracts. UD had lower right superior longitudinal fasciculus (SLF) (temporal) axial diffusivity (AD) (1.14 vs 1.17 (BPII), 1.16 (HC); F = 6.93, 95% CI of [Formula: see text]: 0.00073, 5.22, ηp2 = 0.15). Principal component analysis followed by exploratory linear discriminant analysis showed that increased R-SLF (temporal) AD, YMRS and family bipolarity distinguished BPII from UD (81.5% sensitivity, 85.2% specificity) independent of episode number and frequency. Young, medication-naïve adults with BPII depression did not show the WM disruptions distinguishing more chronically ill BP patients from UD. These WM disruptions may therefore be partly attributable to illness chronicity. Longitudinal studies should examine the trajectory of WM changes in BPII and UD and predictive validity of these baseline clinical and imaging parameters.

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White matter abnormalities in adults with bipolar disorder type-II and unipolar depression.

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