The First Study Of Brain Structure And Functional Connection Changes In Patients With Untreated Depression

Major depressive disorder is characterized by abnormalities in structural and functional circuits.However,structural and functional abnormality findings have been inconsistent.The relationship between structural abnormalities and how structural changes lead to progressive morphometric alterations in depressed brain regions remains unclear.How the resting-state functional connections between the brain regions which have gray matter alteration also remains unclear.In the current study,we recruited untreated first-episode depression patients and healthy control participants indicated to detect the structural and functional alterations specific in first-episode medication-naive major depressive disorder.We chose Voxel-based morphometry analysis,Stage-specific comparation,Structural covariance network analysis,Causal network of structural covariance analysis and resting-state functional connectivity analysis as the major methods in the current study.The results showed:(1)Voxel-based morphometry analysis of high-resolution T1-weighted images was performed to extract the gray matter images of untreated first-episode depression patients and the healthy control participants.Compared to the HC group with a lower threshold(p<.01,FWE corrected),gray matter volume was greater in the bilateral amygdala,the bilateral hippocampus,the bilateral parahippocampus,and the right fusiform in untreated first-episode depression patients,while volume was atrophied in the bilateral brainstem,the bilateral pallidum,and the bilateral thalamus.(2)Stage-specific analysis showed both Stage 1 and Stage 2 showed the gray matter alterations of the amygdala,the hippocampus,the thalamus,the brainstem and the pallidum.However,compared with Stage 1,the gray matter expanded area of hippocampus and amygdala were atrophied(p<.01,FWE corrected).(3)Correlation analysis was performed between gray matter images and illness duration,HRSD scores.Gray matter alterations in the left inferior parietal lobe,the left inferior temporal lobe and the bilateral fusiform positively correlated with illness duration while the gray matter alterations of the bilateral hippocampus negatively correlated with the illness duration(p<.05,FDR corrected).(4)Structural covariance network analysis and Causal network of structural covariance analysis were performed based on cross-sectional morphometric data of the major depressive group(p<.05,FDR corrected).The seed region was selected from the hippocampus,which showed significantly expanded gray matter volume.The bilateral insula,bilateral temporal lobe,anterior cingulate cortex,and posterior cingulate cortex demonstrated synchronized gray alterations with the bilateral hippocampus in major depressive disorder patients.There were causal effect between the bilateral hippocampus and the precuneus,the left middle temporal lobe,the right angular,the left inferior parietal lobe,the postcentral,the right amygdala,and the left inferior parietal lobe and all the nodes belong to default mode network(p<.05,FDR corrected).(5)Seed at right hippocampus,left hippocampus,and the key nodes of default mode network:left precuneus,right precuneus,right posterior cingulate cortex,left posterior cingulate cortex,right mid-temporal lode,left mid-temporal lode,right angular gyrus and left angular gyrus,the ROI-based functional connectivity analysis was performed.The function connection coefficients of left hippocampus and all the other nodes were extracted out,and the function connection coefficients of right hippocampus and all the other nodes were also extracted out.Nonparametric Mann-Whitney U-test and spearman correlation test showed that the function connection coefficients of hippocampus and the other nodes of default mode network were abnormal.The coefficients correlated with HRSD score.Untreated first-episode depression patients showed brain gray matter alterations.The gray matter alterations were stage dependent and developed with the illness duration.The gray matter and functional connectivity of the nodes of default mode network were both abnormal in the untreated first-episode depression patients.The illness duration could better reflect the alterations of the gray matter while the HRSD score could better reflect the alterations of resting-state functional connectivity in untreated first-episode depression patients.The difference has certain significance for the clinical treatment of the major depressive disorder.