A Multi-modal Study On The Reward Network For Adolescent Depression With Or Without Suicide Attempts

PART ONE YOUTH MAJOR DEPRESSIVE DISORDER WITH OR WITHOUT SUICIDE ATTEMPTS STUDY ON STRUCTURE AND COVARIANT OF REWARD NETWORKObjective: to observe the brain structure volume and density of reward network area,and explore the brain structure abnormality of reward network in young MDD patients with and without suicide attempt based on the method of gray matter volume structure co-variation.Methods: 41 cases of young MDD patients who attempted suicide(sMDD group),44 cases of young MDD patients who did not attempt suicide(nMDD group),and 52 healthy controls matched by gender,age and years of education(HC group)were evaluated by psychological scale and resting state fMRI scan.DPABI software was used to analyze the volume and density of gray matter,extract the region of interest(ROI)and compare the differences among the three groups,and calculate the covariant connection strength between the two ROI by partial correlation method.Results: 1.Demographic data and clinical psychological scale analysis showed that one-way anova and chi-square test showed no statistically significant differences among sMDD,nMDD and HC groups in gender(P= 0.623),age(P= 0.508)and years of education(P=0.721).However,the HAMD and SSI scores of the sMDD group andthe nMDD group were significantly higher than those of the HC group,and there was a significant statistical difference in the scores of the three groups(P<0.001).Post-analysis showed no statistical difference in the HAMD and SSI total score of the sMDD group and the nMDD group.2.Anova results of gray matter density and volume in the seed area of the reward network showed statistically significant differences in the gray matter density of the bilateral striatum(P < 0.05),and post-morter examination showed statistically significant differences in the bilateral ventral striatum between the nMDD group and the HC group(P =0.001 and0.005,respectively).The variance analysis of gray matter volume showed no significant difference between groups.3.The structural covariant model analysis found that the strength of the gray matter volume connection between the ventral striatum and the anterior cingulate gyrus increased in the young MDD patients with a suicide attempt,while the strength of the gray matter volume connection between the ventromedial prefrontal cortex and the anterior cingulate gyrus decreased in the young MDD patients without a suicide attempt.4.The correlation analysis between gray matter structure and clinical psychological scale showed there was a significant positive correlation between the gray matter density of l-vs in sMDD group and the score of SSI.Conclusions: changes in gray matter density in the bilateral striatum in young MDD patients may mediate the function of reward circuits,which may influence MDD symptoms.PART TWO LOCAL BRAIN FUNCTION OF REWARD CIRCUITS IN YOUTH DEPRESSION WITH OR WITHOUT SUICIDAL ATTEMPTSObjective: Re Ho,ALFF and DC analysis were used to evaluate the reward network brain activity patterns in young MDD patients,and to understand the pathological mechanism of young MDD with or without suicidal behaviors from different perspectives.Methods: ALFF,Re Ho and DC analysis were conducted on the pre-processed f MRI data by using various modules in the software version DPABI4.2,and 11 ROI values of the reward network were extracted.ANOVA method was used for statistical analysis in SPSS.In addition,correlation analysis was conducted with clinical psychological assessment scale(HAMD,SSI)scores to investigate the correlation between brain regions with abnormal functional activity and clinical symptoms.Results: 1.The comparison of ALFF ANOVA analysis between the three groups revealed statistically significant differences in the m PFC(P <0.05),while post-mortem examination revealed statistically significant differences between the ventral prefrontal cortex n MDD group and HC group(P =0.031).2.The comparison between the Re Ho ANOVA groups showed statistically significant differences in the left striatum and ventromedial prefrontal cortex(P < 0.05),and the post-mortem examination showed statistically significant differences in Re Ho between the n MDD group and the HC group(P =0.018 and 0.025,respectively).3.The variance analysis of the DC seed region of the reward network did not find significant inter-group differences.4.The correlation analysis between the Re Ho values of different brain regions and the scale showed a significant negative correlation between the score of item 7 of anhedonia in the n MDD group(0-4 points)and the mean Re Ho of vm PFC(r=-0.65,P<0.05).Conclusions: Changes in the ALFF and Re Ho values in the ventral striatum and ventromedial prefrontal cortex in young MDD patients suggest that two important nodes of the reward network have local network function changes in young MDD patients,which may affect the reward system by altering cognition,leading to the emergence of the core symptom of MDD,anhedonia.PART THREE A STUDY OF REWARD NETWORKS AND FUNCTIONAL CONNECIONS WITH THE WHOLE BRAIN IN ADOLESCENTS WITH AND WITHOUT SUICIDAL STTEMPTSObjective: Based on the functional connectivity analysis method of region of interest(ROI),the functional connectivity map between ROI or ROI region and the whole brain was constructed.The reward network was observed to change functional connectivity and its relationship to clinical symptoms in young MDD patients with and without suicide attempts.Methods: The average time series of ROI brain regions were extracted,and then the correlation analysis of 11 ROI time series was carried out in pairs,and the correlation coefficients were extracted as functional connection graphs.The 11 ROI time series and the rest of the voxel of the whole brain were analyzed by Pearson correlation,and Fisher’s Z transformation was carried out to obtain the functional connectivity map of ROI and the whole brain.Pearson correlation analysis was conducted with the score of the clinical psychological assessment scale to explore the correlation between these abnormal active brain areas and clinical symptoms.Results: 1.11 ROI extraction time sequence,and the whole brain do correlation analysis,the results found in the change of FC in the following three regions: the ventral tegmental area and the function of the frontal lobe connection increases,the difference area as a MASK to extract the FC value inside the MASK,using SPSS16.0 do one-way ANOVA analysis,Bonferroni afterwards,according to the results of analysis n MDD and HC there are significant difference between,with statistical significance(p <0.001);There were significant differences in the FC subregions of ACCsuperior frontal gyrus among the three groups of ACC.In addition,there were significant differences in FC between pre sg ACC-cauda_L and pg ACC-island_L.The FC between the pre-SMA and bilateral temporal lobe and insula_L were altered.2.FC between ROI: FC between ROI1(VS_L)and ROI9(preSMA)was statistically significant(p=0.037),and post-morter analysis revealed statistically significant differences between s MDD and Nmdd group(p=0.038).There were statistically significant differences in FC between ROI2(VS_R)and ROI9(pre SMA)(p=0.039),and post-morter analysis revealed statistically significant differences between s MDD and n MDD(p=0.034).The FC between ROI3(vm PFC)and ROI9(pre SMA)was statistically significant(p=0.006),and the post-morter analysis showed that the FC between ROI3(vm PFC)and ROI9(pre SMA)was statistically significant(p= 0.005).The FC difference between ROI6(PC)and ROI8(AC)was statistically significant(p=0.021),and post-analysis showed that the FC difference between ROI6(PC)and ROI8(AC)between s MDD and HC was statistically significant(p= 0.017).The FC difference between ROI8(AC)and ROI9(pre SMA)was statistically significant(p=0.018),and the post-analysis showed that the FC difference between ROI8(AC)and ROI9(pre-SMA)between s MDD and HC was statistically significant(p=0.026).3.An independent correlation analysis was conducted between the SSI and MDD and the different brain regions,and the results showed that in the n MDD group,the reduction of FC in pg ACC-superior frontal gyrus was positively correlated with suicidal ideation(p<0.05).Conclusions: Associated with suicide attempts of young patients with MDD button is back,sports area,the ventral striatum and the ventromedial prefrontal cortex,partial and whole brain function relation between the function of connection and ROI were found differences,although patients with attempted suicide,change in local structure and function is not obvious,but the total reward network can connect multiple core node changes,it is closely related to the occurrence of MDD shape may.PART FOUR A DYNAMIC STUDY ON THE LOCAL AND FUNCTIONAL CONNECTIONS OF REWARD NETWORK IN YOUTH WITH AND WITHOUT SUICIDAL ATTEMPTSObjective: Focusing on the dynamic characteristics of local resting state indicators(such as ALFF,Re Ho,DC)and functional connectivity,this study systematically explored the abnormal characteristics of local neural activity and network functional connectivity indicators in young patients with or without suicide attempts compared with normal controls.Methods: The Temporal Dynamic Analysis software package in DPABI was used for data processing,and the mean and standard deviation between sliding Windows were calculated to characterize the variability of Dynamic FC.The statistical analysis method of ANOVA was used to calculate the statistical significance of the differences among the three groups in SPSS,and the post-test was conducted.The correlation between the change of index dynamic characteristics and MDD shape and suicide was analyzed.Results: 1.Variance analysis of ALFF dynamics in the ROI of the reward network revealed that there were statistically significant differences in bilateral striatum and vm PFC.Bonferroni post-test revealed that the three ROIs were all statistically significant differences between n MDD and HC groups(all p <0.05).2.The results of dynamic Re Ho analysis of variance(ANOVA)showed that there were statistically significant differences in the left striatum and ACC 、 PCC(both P < 0.05).Bonferroni post-mortem test showed that both ROIs were statistically significant differences in Re Ho dynamics between n MDD and HC groups(p<0.05).3.For the DC dynamic analysis of ROI based on reward network among the three groups,no significant inter-group difference was found.4.The results of dynamic FC indicated that the dynamic of FC between the left ventral striatum and the putamen changed.Bonferroni’s post hoc analysis showed that the differences between s MDD and n MDD groups and between n MDD and HC groups were statistically significant(all p <0.001).The dynamics of FC between the left anterior insula and the left medial superior frontal gyrus changed,with significant differences between s MDD and HC groups and between n MDD and HC groups(p<0.001 and p=0.001,respectively).The dynamics of FC between the right anterior insula,the right central anterior gyrus and the left medial superior frontal gyrus changed.The differences between s MDD and HC groups and between n MDD and HC groups were statistically significant(p <0.001,p=0.002,respectively).The differences between Smdd,n MDD and HC groups were statistically significant(p<0.001).The dynamic FC between the ventral tegmental area and the right occipital cortex changed,and the differences between s MDD and HC groups and between n MDD and HC groups were statistically significant(p=0.049,0.001).The dynamics of FC between the pre-SMA and the inferior frontal gyrus changed,and the differences between s MDD and HC groups were statistically significant(p=0.022).Conclusions: Associated with suicide attempts of young patients with MDD in the ventral striatum left,left and right anterior insula,the ventral tegmental area,movement area such as core node and the function of the whole brain reward network connection is obvious dynamic change,and the local characteristics of the dynamic change only found not associated with suicide attempts of young patients with MDD in the core area of the change,this hint associated with suicide attempts of the dynamic characteristics of young patients with MDD rewards network revealed extensive changes,the change of the network can occur prior to the function of the local.