To assese the whole-brain functional connectivity patterns in patients with refractory depressive disorder (RDD) and non-refractory depressive disorder (NDD) by using resting state functional connectivity MRI.

Sixty-four major depressive disorder patients who had not received antidepressant treatment and 48 healthy control (HC) subjects underwent a resting-state functional magnetic resonance imaging scan (R-fMRI). Patients were treated with antidepressant after MR imaging for 6 weeks. The NDD was defined as a reduction of HAMD score more than 50% after treatment. Finally, 24 patients with RDD, 40 patients with NDD were identified. Image preprocessing was carried out using Statistical Parametric Mapping (SPM8, http://www.fil.ion.ucl.ac.uk/spm) and Data Processing Assistant for Resting-State fMRI (DPARSF). Then, whole-brain functional connectivity strength (FCS) analysis was performed to estimate the global communicational capacity of brain regions. Statistical analysis was performed using a voxel-based, one-way analysis of covariance (ANCOVA) with age and gender as covariates, followed by two-sample t-tests post-hoc. The general linear model analyses were also performed between the HAMD scores and FCS in each of the patient group.Relative to HC group, RDD group showed significantly reduced FCS mainly in the cortical regions (Figure 1B); while RDD group showed significantly increased FCS in the cortical-limbic circuits when compared with NDD group (Figure 1D). Meanwhile, compared with the HC group, NDD demonstrated decreased FCS within cortical-limbic-thalamic circuits (Figure 1C). In the group with RDD, positive correlation between the Hamilton Depression Rating Scale scores and FCS values in the bilateral cuneus and the right calcarine fissure were also observed (Figure 2).We used R-fMRI and functional connectivity strength mapping approaches to study whole-brain networks in the RDD, NDD and healthy controls. Both the RDD and NDD groups demonstrated lower FCS in the cortical regions when compared with HC group. Some differences between RDD and NDD patients which might be used to distinguish these two conditions. The alteration of FCS in NDD group was mainly located in the medial frontal gyrus while the alterations of RDD group were located in the non-medial frontal areas although both groups observed altered FCS in the frontal areas. Additionally, compared with the HC group, NDD demonstrated lower FCS in the limbic regions which was not obvious in the RDD group. Meanwhile, lower FCS in the default mode network (DMN) and visual recognition network was observed in the group with NDD when compared with the group with RDD. Finally, we observed positive correlations between the HAMD scores and FCS values in the bilateral cuneus and the right calcarine fissure in group with RDD.In conclusion, the cortical brain regions showed abnormal FCS in both patient groups might be the intrinsic brain regions that should have changed in MDD. When compared with HC, the alteration of FCS in NDD group was mainly located in the medial frontal gyrus while the alterations of RDD group were located in the non-medial frontal areas and NDD demonstrated lower FCS in the limbic regions which was not obvious in the RDD group. These might suggest that patients with RDD can be treated by the treatment methods target non-medial frontal areas and explain why not all depressed patients are sensitive to the pharmacological treatment even treated by the same psychiatrist. Lower FCS in the DMN and visual recognition network was observed in the group with NDD when compared with the group with RDD. These results suggest that RDD and NDD are characterized by distinct functional deficits in distributed brain regions or brain networks.