Abnormal white matter integrity in Chinese young adults with first-episode medication-free anxious depression: a possible neurological biomarker of subtype major depressive disorder

BACKGROUND: Almost half of patients with major depressive disorder (MDD) also have clinically meaningful levels of anxiety. Anxious depression is a distinct clinical subtype of MDD, which has poor response to pharmacotherapy; however, the neural mechanisms behind are largely unknown. In the present study, we explored the white matter (WM) integrity traits of anxious depression in first-episode and medication-free (medication-naïve and medication washout) Chinese young adult patients by detecting differences in diffusion tensor imaging (DTI) with the tract-based spatial statistics (TBSS) method. SUBJECTS AND METHODS: DTI was obtained from 39 first-episode, medication-free anxious depressive patients, 45 nonanxious depressive patients, and 50 demographically similar healthy controls. All subjects underwent clinical assessments. TBSS was carried out to investigate the difference in WM integrity among three groups within DTI parameter maps. WM integrity was measured using fractional anisotropy (FA), mean diffusivity, axial diffusivity, and radial diffusivity (RD). The correlations between WM integrity and clinical features were also computed. RESULTS: When compared with nonanxious patients, lower FA values in anxious depressive patients were found in multiple regions of the brain, mainly involving left uncinate fasciculus (UF), superior longitudinal fasciculus (SLF), and forceps major and minor. Higher RD in forceps major and minor and SLF were also detected. The decreased FA values and increased RD values correlated with both anxiety level and depression level in the pooled depressive group. CONCLUSION: The anxious depressive patients had more abnormalities in WM integrity at the early phase than the nonanxious group. Alternations in WM integrity in fiber pathways, including SLF, UF, and forceps major and minor, may play a critical role in the neuropathology of anxious depression and might help to identify anxious MDD from nonanxious MDD. Further study with larger sample size, larger age range, and longitudinal design is needed to confer a robust inference to better understand the dynamic neurological change and neuropathology of WM integrity in anxious MDD.