| Background and objective: Suicide in adolescence is an extremely serious social problem.Major depressive disorder(MDD)is one of the main reasons of suicide in adolescents.In terms of suicide risk,the common suicide and self-injury behaviors including non-suicidal self-injury(NSSI)and suicide attempt(SA),have a significant interaction effect with MDD in adolescents with MDD,which are considered to be important precursors to suicide in the future.However,the current assessment of suicide risk is mainly based on numerous socio-demographic and clinical risk factors,which usually have high sensitivity and low specificity.The specific neurobiological markers combined with clinical assessment will contribute to predict the future suicide risk of adolescents with suicide and self-injury behaviors.The frontal-limbic circuitry plays an important role in the regulation of emotion,cognition,and behavior.Our previous studies on the adolescents with SA and adolescents with MDD have found abnormal local neural activity and resting-state functional connectivity(rs-FC)in multiple brain regions of the frontal-limbic circuitry,such as the frontal gyrus and insula gyrus.In the present study,the multimodal magnetic resonance imaging(MRI)was used to investigate the changes of structure and function in the frontal-limbic circuitry in MDD adolescents with NSSI behavior and MDD adolescents with different self-injury behavior patterns in the resting state.It is expected that it can find the neurobiological markers of early NSSI behavior in adolescents with MDD and explore the differences of different suicide and self-injury behaviors patterns for identifying and assessing early the propensity or risk of future suicide in adolescents with MDD,providing the objective evidence of suicide warning,developing the preventive psychological intervention strategies for the pathogenesis of the disease,and providing the objective basis for clinical prevention and treatment.Methods: The subjects included 43 MDD adolescents with NSSI behavior(NSSI group)and 29 MDD adolescents without NSSI behavior(MDD group)in part 1,and 22 MDD adolescents with SA and NSSI behaviors,29 MDD adolescents with SA behavior only,and 43 MDD adolescents with NSSI behavior only in part 2 were conducted for further clinical psychological evaluation and resting-state MRI scan.The voxel-based morphometry(VBM)method was used to analyze the differences of gray matter volume(GMV)in the 102 Seeds of 9 regions of interest(ROI)in the frontal-limbic circuitry.For preprocessed functional MRI(f MRI)data,the amplitude of low-frequency fluctuation(ALFF),regional homogeneity(Re Ho),and fractional amplitude of low-frequency fluctuation(f ALFF)analyses were used to investigate the differences of local neural activity in the frontal-limbic circuitry.The FC analysis was used to investigate the differences of time series correlations between each Seed in the frontal-limbic circuitry and whole-brain voxels.To evaluate the correlation between structural or functional abnormalities in brain regions and clinical symptoms,the Pearson correlation analysis was used to calculate the correlation between the altered GMV,ALFF,Re Ho,f ALFF and rs-FC values and HAMD,BIS-11,SSI scores.Results: 1.The demographic data and clinical scales of the MDD adolescents with or without NSSI behavior(NSSI and MDD groups)and MDD adolescents with different self-injury behavior patterns(NSSI+SA,SA,and NSSI groups)were compared,respectively.In the NSSI and MDD groups,there were no significant differences in gender(p=0.369),age(p=0.329),education level(p=0.559),and disease duration(p=0.171).In terms of clinical scale scores,there were no significant differences in HAMD(p=0.618)and SSI(p=0.103)scores,but BIS-11(p<0.001)scores of the NSSI group was significantly higher than that of MDD group.In the NSSI+SA,SA,and NSSI groups,there were no significant differences in gender(p=0.472),age(p=0.268),education level(p=0.267),and disease duration(p=0.639).In terms of clinical scale scores,there were no significant differences in HAMD scores(p=0.226),but SSI(p<0.01)and BIS-11(p<0.001)scores were significantly different.Post-hoc t test found that the BIS-11 score in the NSSI+SA and NSSI groups was obviously higher than that in the SA group(p<0.001,p<0.01).On the other hand,the SSI score in the NSSI+SA group was obviously higher than that in the SA and NSSI groups(p<0.05,p<0.001).2.The structural MRI(s MRI)studies in the NSSI and MDD groups showed that compared with the MDD group,the GMV in the left middle frontal gyrus(MFG Seed 13),right inferior frontal gyrus(IFG Seed 8),right Orbital gyrus(Or G Seed 12),bilateral insula(INS Seed 1,INS Seed2),and left hippocampus(Hipp Seed 3)were significantly decreased in the NSSI group(p<0.05,p<0.05,p<0.01,p<0.05,p<0.05,p<0.05).The structural MRI(s MRI)studies in the NSSI+SA,SA and NSSI groups showed that compared with the NSSI group,the GMV in the right superior frontal gyrus(SFG Seed 2)and right MFG(MFG Seed 6)were significantly decreased in the NSSI+SA group(p<0.01,p<0.05),and compared with the SA and NSSI groups,the GMV in the left Or G(Or G Seed 3),right INS(INS Seed 8),and right Hipp(Hipp Seed 2)were also significantly decreased in the NSSI+SA group(p<0.05,p<0.05;p<0.001,p<0.001;p<0.001,p<0.001).However,there was no significant difference between the SA and NSSI groups(p>0.05).3.The functional MRI(f MRI)technique was used to detected the local neural activity in the NSSI and MDD groups.ALFF analysis found that compared with the MDD group,the NSSI group had a significantly higher ALFF value in the left orbital part of middle frontal gyrus/orbital part of superior frontal gyrus cluster(p<0.001).Re Ho analysis found that compared with the MDD group,the Re Ho value in the right triangular part of inferior frontal gyrus was also significantly increased in the NSSI group(p<0.05).However,f ALFF analysis found that there were no significant differences in f ALFF values between the two groups(p>0.05).The local neural activity in the NSSI+SA,SA and NSSI groups was also detected by f MRI technique.ALFF analysis found that there were no significant differences in ALFF values in the three groups(p>0.05).Re Ho analysis found that the Re Ho value in the right orbital part of inferior frontal gyrus was significantly higher in the NSSI+SA group than that in the SA group;moreover,it were also significantly higher in the right orbital part of middle frontal gyrus and orbital part of inferior frontal gyrus cluster in the NSSI+SA group than that in the NSSI group;finally,compared with the NSSI group,the Re Ho values in the right orbital part of middle frontal gyrus and orbital part of inferior frontal gyrus cluster were also obviously increased in the SA group(all p<0.05).f ALFF analysis found that the f ALFF value in the right triangular part of inferior frontal gyrus was significantly higher in the NSSI+SA group than that in the SA group;moreover,it was also significantly higher in the bilateral triangular part of inferior frontal gyrus in the NSSI+SA group than that in the NSSI group;finally,compared with the NSSI group,the f ALFF value in the left triangular part of inferior frontal gyrus was also obviously increased in the SA group(all p<0.05).4.The f MRI technique was used to analyze the rs-FC between 102 Seeds of the frontal-limbic circuitry and whole brain in the NSSI and MDD groups.Compared with the MDD group,rs-FC of the right orbital gyrus(Or G Seed 2)-bilateral supplementary motor area/left paracentral lobule cluster and the left orbital gyrus(Or G Seed 9)-left precentral gyrus were significantly decreased(all p<0.05);moreover,rs-FC of the left amygdala(Amyg Seed 1)-right middle occipital gyrus/middle temporal gyrus cluster,the left amygdala(Amyg Seed 3)-left anterior cingulate and paracingulate gyri,and the right amygdala(Amyg Seed 4)-right middle temporal gyrus/middle frontal gyrus/orbital part of inferior frontal gyrus cluster were also significantly decreased in the NSSI group(all p<0.05);in addition,the rs-FC of the left insula(INS Seed 7)-bilateral anterior cingulate and paracingulate gyri and the left insula(INS Seed 9)-triangular part of inferior frontal gyrus/orbital part of inferior frontal gyrus cluster were also decreased(all p<0.05);finally,the rs-FC analysis based on the four subregions of hippocampus showed that the rs-FC of the left hippocampus(Hipp Seed 1)-left orbital part of frontal gyrus were significantly decreased in the NSSI group(p<0.05).The f MRI technique was also used to analyze the rs-FC between 102 Seeds of the frontal-limbic circuitry and whole brain in the NSSI+SA,SA and NSSI groups.Compared with the SA and NSSI groups,the rs-FC of the right SFG(SFG Seed 14)-right superior temporal gyrus/middle temporal gyrus cluster was significantly decreased in the NSSI+SA group(p<0.001,p<0.05);however,compared with the NSSI group,the rs-FC of the right SFG(SFG Seed 14)-right superior temporal gyrus/middle temporal gyrus cluster was also obviously increased in the SA group(p<0.01).In addition,compared with the SA and NSSI groups,the rs-FC of the right Or G(Or G Seed 8)-right superior temporal gyrus was significantly decreased in the NSSI+SA group(p<0.001,p<0.001);however,compared with the NSSI group,the the rs-FC of the Or G Seed8-right superior temporal gyrus was also obviously increased in the SA group(p<0.01).5.Correlation analysis between the altered regions and clinical scales in the NSSI and MDD groups showed that the averaged GMV of the right MFG(MFG Seed 13)was significantly positively correlated with the HAMD scores in the MDD group(r=0.466,p=0.011);however,the averaged GMV of the right Or G(Or G Seed 12)and right INS(INS Seed 2)were significantly negatively correlated with BIS-11 scores(r=-0.305,p=0.047;r=-0.307,p=0.046).Correlation analysis between the altered regions and clinical scales in the NSSI+SA,SA and NSSI groups showed that the rs-FC of the right SFG(SFG Seed 14)-right superior temporal gyrus/middle temporal gyrus was significantly negatively correlated with the BIS-11 scores in the NSSI+SA group(r=-0.423,p=0.049);however,the averaged GMV of the left Or G(Or G Seed 3)was significantly negatively correlated with the HAMD scores in the NSSI group(r=-0.373,p=0.014).Conclusions: 1.The differences of GMV in the frontal-limbic circuitry including MFG,Or G and INS may be the basis of functional changes of frontal-limbic circuitry in MDD adolescents with NSSI behavior and MDD adolescents with different self-injury behavior patterns.2.The changes of local neural activity and rs-FC in multiple regions of frontal-limbic circuitry in MDD adolescents with NSSI behavior and MDD adolescents with different self-injury behavior patterns suggest that the frontal-limbic circuitry may affect the suicide and self-injury behaviors in adolescents with MDD by modulating emotional regulation,cognitive control,and impulsive response processes,and the functional differences of MDD adolescents with different suicide and self-injury behavior patterns are helpful to understand the neurobiological differences.3.The correlation analysis found that,the changes of GMV in the left MFG may have effect on the severity of depressive symptoms in adolescents with MDD,and the decrease of GMV in the right Or G and right INS may contribute to increased impulsivity in MDD adolescents with NSSI behavior.In addition,the decreased rs-FC of the right SFG-right superior temporal gyrus/middle temporal gyrus may be the basis of increased impulsivity in MDD adolescents with SA and NSSI behavior;the decreased GMV in the left Or G may also be related with severity of depressive symptoms in MDD adolescents with NSSI behavior. |
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