Shared and distinctive changes of the white matter integrity in generalized anxiety disorder with or without...

Generalized anxiety disorder (GAD) is a prevalent anxiety disorder often comorbid with major depressive disorder (MDD). Previous neuroimaging studies have shown that white matter (WM) microstructural alterations are critical for efficient communication between brain regions, and play an important role in the pathology of GAD. However, the exact profile of WM abnormalities in GAD with and without comorbid MDD remain unclear. This study aimed to uncover them using a novel global probabilistic tractography technology named Tracts Constrained by Underlying Anatomy (TRACULA), and to assess the correlations between fascicle integrity and symptom severity.

We recruited 20 pure GAD (p-GAD) patients, 14 GAD comorbid with MDD (GAD + MDD) patients, and 41 age- and sex-matched healthy controls (HCs). All participants underwent T1 magnetic resonance imaging and diffusion tensor imaging. For each subject, 42 WM fiber bundles of the whole brain were successfully tracked and calculated with five metrics including volume, fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD). Group comparison were firstly performed between the whole GAD patients and HCs. Then, we compared the differences among the three groups (the p-GAD, GAD + MDD patients and HCs) using the one-way ANCOVA and post hoc analysis with the Bonferroni correction. Furthermore, correlations between abnormal WM metrics and clinical symptom severity were examined using partial correlations analyses among patients.

Compare to HCs, both p-GAD and GAD + MDD patients exhibited decreased FA values in left superior longitudinal fasciculus (SLF) II, and right dorsal of cingulum bundle (CBD); Moreover, GAD + MDD patients showed decreased FA, increased MD and RD values in the central and temporal section of the body of the corpus callosum (CC-BODY), right SLF I and II compared to HCs. Within the GAD + MDD group, GAD-7 scores were negatively correlated with FA values (r = -0.75, p = 0.008) and positively correlated with RD values (r = 0.7, p = 0.017) in the right CBD.

This study identified both shared and distinctive changes in GAD patients with and without MDD. The shared WM disruption in the p-GAD and GAD + MDD groups located in the left SLF and right CBD, while only GAD + MDD patients showed distinctive changes in the central and temporal sections of the CC-BODY and right SLF. Current study gave a comprehensive characterization of WM abnormalities among these patients, and highlighted TRACULA's value in identifying critical WM changes.