Voxel-wise brain-wide functional connectivity abnormalities in first-episode, drug-naive patients with major depressive disorder

Due to different foci and single sample across studies, abnormal functional connectivity (FC) has been implicated in the pathophysiology of major depressive disorder (MDD) with inconsistent results. The inconsistency may reflect a combination of clinical and methodological variability, which leads to limited reproducibility of these findings. The samples included 59 patients with MDD and 31 controls from Sample 1, 29 patients with MDD and 24 controls from Sample 2, and 31 patients with schizophrenia and 37 controls from Sample 3. Global-brain FC (GFC) and an overlapping technique were applied to analyze the imaging data. Compared with healthy controls, patients with MDD in Samples 1 and 2 showed increased GFC in the overlapped brain areas, including the bilateral insula, right inferior parietal lobule (IPL), and right supramarginal gyrus/IPL. By contrast, decreased GFC in the overlapped brain areas, including the bilateral posterior cingulate cortex/presuneus and left calcarine cortex, was found in patients with MDD. In addition, patients with schizophrenia in Sample 3 did not show any GFC abnormalities in the overlapped areas from the results of Samples 1 and 2. The present study is the first to examine voxel-wise brain-wide FC in MDD with two independent samples by using an overlapping technique. The results indicate that aberrant FC patterns of insula-centered sensorimotor circuit may account for the pathophysiology of MDD.