Correlation Between Habenular Nucleus And Whole Brain Function As Well As Clinical Features In First-episode Non-Medication Depression Patients

Objective:Previous studies on animal models of depression have demonstrated that the Habenula Nucleus(Hb)plays an important role in the pathogenesis of Major depressive disorder(MDD),and its mechanism may be due to the effect of Hb cluster discharge on cerebral neural circuit.However,there is lack of in-depth study on the specific causes of Hb affecting cerebral neural circuit in MDD patients.In addition,there is a lack of research on relevant clinical features.Therefore,in this study,Resting-State Functional Magnetic Resonance Imaging(rs-fMRI)imaging technology was used to explore the differences between Hb and whole brain function connectivity(FC)in patients with first-episode non-drug-taking MDD and their correlation with clinical features,as well as the pathogenesis of Hb in MDD.Methods:This case-control study was conducted.The case group included 265 MDD patients who did not take medicine as the first episode in the database of the Department of Psychiatry of the First Affiliated Hospital of Kunming Medical University from December 2011 to August 2015,which met the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders(Fourth Edition,DSM-IV)in the United States as the control group.Based on the MATLAB R2015b software platform,the original images of the MDD group and the health control(HC)were converted from DICOM format to NIFTI format using MRIconvert software,and the left and right HBs were selected as the regions of interest,respectively.The image preprocessing was performed on the magnetic resonance data of the two groups using DPABI software,and the time sequence of the region of interest was extracted.The correlation analysis was also performed on the extracted time sequence of the two HBs and the time sequence of the whole brain,respectively.Except for the data of incomplete information,data loss and incomplete skull stripping,154 cases were included in the MDD group and 295 cases were included in the HC group.With gender,age and educational year as covariates,the ipsilateral results were compared with two-sample t-test,to obtain the differential brain regions of bilateral Hb and whole brain FC,respectively.The rex software was used to extract the values of the differential brain regions.On the platform of SPSS 22.0 software,Pearson correlation analysis was performed on the FC value of different cerebral regions with the course of disease,the total scores of HAMD-17 and HAMA-14.The short-term course of disease was defined as the course of disease of less than or equal to 6 months in the MDD group,the course of disease between 6 months and 24 months was defined as the medium-term and long-term course of disease,and the course of disease of greater than or equal to 24 months was defined as the chronic course of disease.The one-way analysis of variance was performed with gender,age,and educational attainment as covariates,followed by pairwise comparison(using two-sample t test).The differences of Hb and whole brain FC between patients with short-term course of disease and medium-term and long-term course of disease group,patients with short-term course of disease and chronic course of disease group,and patients with medium-term and long-term course of disease and chronic course of disease group were compared,to further explore the relationship between Hb and whole brain FC in patients with MDD and the correlation between clinical characteristics of MDD and changes in brain function.Results:1.Compared with the HC group,the left Hb and the right straight gyrus(x,y,z=3,27,-15,t=4.0814,P<0.05)in the MDD group were increased,while the FC of the left anterior central gyrus(x,y,z=-33,6,42,t=4.1622,P<0.05)was increased.It weakened FC with the right leguminous putamen(x,y,z=27,3,12,t=-3.5168,P<0.05).2.Compared with HC group,right Hb and right middle temporal gyrus(x,y,z=36,-66,15,t=3.7298,P<0.05)and left middle temporal gyrus(x,y,z=-36,-42,9,t=3.8128,P<0.05)FC were increased in MDD group.Fc was weaker than that in the right spinous process(x,y,z=21,9,15,t=-4.5495,P<0.05),the left medial brain,and the cingulate gyrus(x,y,z=0,-12,45,t=-3.7397,P<0.05).3.After pairwise comparison of the three groups of patients with different disease courses,no disease-related differential brain regions in left Hb were found.compared with the chronic disease course group,the short-term disease course group exhibited weaker fc in the right Hb and right dorsolateral frontal gyrus(x,y,z=18,12,60,t=-4.046,p<0.05),left brain accessory motor area(x,y,z=-9,0,63,t=-4.5758,p<0.05).Compared with the chronic disease course group,the long-term disease course group exhibited weaker FC in the right Hb and right precuneus(x、y、z=15、-63、24,t=-4.2758,P<0.05).4.Pearson correlation analysis showed that the FC values of left Hb and the whole brain in MDD patients were positively correlated with the course of the disease(r=0.16,P=0.05).Conclusion:1.There were changes in Hb and whole brain FC in the first-episode non-drug-taking MDD patients in resting state,and this abnormal trend of FC may be involved in the pathophysiological mechanism of MDD.2.In patients with MDD,left and right Hb functions are lateralized,which is imbalanced with whole brain FC,and there is difference in executive function,which tends to be complementary or inhibitory.3.The longer the course of disease was in the MDD group,the stronger the Hb on the right side and FC in different brain regions were,which might be related to the clinical characteristics of loss of pleasant sensation,decreased activity and memory decline in MDD patients.