Desynchronized white matter function and structure in drug-naive first-episode major depressive disorder patients

Major depressive disorder (MDD) is a highly prevalent mental disease. Using magnetic resonance imaging (MRI), although numerous studies have revealed the alterations in structure and function of grey matter (GM), few studies focused on the synchronization of white matter (WM) structure and function in MDD. The aim of this study was to investigate whether functional and structural abnormalities of WM play an essential role in the neurobiological mechanisms of MDD.

Gradient-echo imaging sequences at 3.0T were used to gather resting state functional MRI (rsfMRI) data, which were performed on 33 drug-naive first-episode MDD patients and 34 healthy controls (HCs). After data preprocessed, amplitude of low frequency fluctuation (ALFF) of WM was calculated. ALFF values in different frequency bands were analyzed, including typical (0.01-0.15 Hz) band, slow-4 (0.027-0.073 Hz) and slow-5 (0.01-0.027 Hz) bands. In addition, the fractional anisotropy (FA) values in WM in 23 patients and 26 HCs were examined using tract-based spatial statistics (TBSS) and tractography based on diffusion tensor imaging (DTI). Pearson correlation analysis was applied to analyze the relationships between ALFF values and Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA).

Compared with the HCs, MDD patients showed decreased ALFF values in posterior thalamic radiation (PTR) and superior longitudinal fasciculus (SLF) in slow-5 frequency band, no significant differences of ALFF values were found in typical and slow-4 frequency bands. In addition, there were no significant differences in FA values with TBSS analysis as well as the number of fibers in PTR and SLF with tractography analysis between two groups. Further correlation analysis showed that the ALFF value in SLF was negatively correlated with HAMA-2 score (r = -0.548, p _FDR = 0.037) in patients.

Our results indicated that WM dysfunction may be associated with the pathophysiological mechanism of depression. Our study also suggested that the functional damage of the WM may precedes the structural damage in first-episode MDD patients. Furthermore, for mental disorders, slow-5 frequency band may be a more sensitive functional indicator for early detection of abnormal spontaneous brain activity in WM.