Altered Variability And Concordance Among Dynamic Resting-state FMRI Indices In Depressed Patients With Anxious Distress

Objective: Major depression disorder(MDD)is one of common mental illnesses.MDD is now considered to be a heterogeneous disorder with different subtypes,and one of these is depression with anxious distress.Depression with anxious distress typically shows an earlier age of onset,more severe depressive symptoms,more recurrent episodes,suicide attempts,worse social functioning,and treatment resistance.Traditional static analysis of fMRI images cannot reflect the continuous fluctuations in the brain.The purpose of this study is to explore the changing patterns of resting-state brain intrinsic activity in patients with depression with anxious distress using dynamic analysis.Methods: A total of 45 depressed patients with anxious distress(MDD/AD+),30 depressed patients without anxiety(MDD/AD-)and 46 healthy controls(HC)were enrolled.Hamilton Depression Scale(HAMD)and Hamilton Anxiety Scale(HAMA)were used to evaluate the symptoms of depression and anxiety in patients.The rs-fMRI data of the subjects were collected,and the dynamic indexes such as low-frequency fluctuation amplitude(ALFF),degree centrality(DC),global signal correlation(GSCorr)and regional homogeneity(Re Ho)were calculated by the sliding time window method.The volume-wise and voxel-wise concordance of the dynamic indices are calculated and compared.Finally,the correlation between voxel-wise concordance and anxiety severity was analyzed.False discovery rate correction(FDR correction)was used for multiple comparison correction,and the statistical thresholds were voxelp < 0.001 and cluster-p < 0.05.Bonferroni correction was used to reduce the rate of false positives for post hoc multiple comparisons.Results: Both patients with MDD/AD+ and MDD/AD-showed decreased ALFF in bilateral calcarine sulcus,left postcentral gyrus and left inferior parietal lobule compared to the HC.Relative to HC,reduced DC was detected in right calcarine sulcus and right lingual gyrus in MDD/AD+ and MDD/AD-group.Decreased GSCorr and Re Ho in right middle occipital gyrus were observed in groups of MDD/AD+ and MDD/AD-compared to HC.Compared to MDD/AD-,decreased voxel-wise concordance in left medial superior frontal gyrus was detected in MDD/AD+ patients.Significant difference in mean values of volume-wise concordance was found among three groups.Moreover,negative correlation between HAMA score and voxel-wise concordance in left medial superior frontal gyrus was found.Conclusions: The results showed that dynamic indices of resting-state fMRI showed different neural activity in different brain regions in patients with depression compared with healthy controls,but no statistically significant differences were found between depressed patients with and without anxiety.Concordance analysis showed that the voxel-wise concordance of left superior frontal gyrus was decreased in depressed patients with anxious distress,and was negatively correlated with HAMA score.This suggests that the abnormal integration and reduced flexibility of this region may be the underlying neurobiological mechanism of anxious distress.