A Study On The Function Of Habenula In Major Depressive Disorder Patients With Suicidal Ideation

Objective:Focusing on characteristics of strength and stability of brain functional connectivity,this study respectively explored the static(sFC)and dynamic functional connectivity(dFC)in adult and adolescent major depressive disorder(MDD)patients with suicidal ideation(SI).Methods:This study was divided into two parts.In the part one,43 and 38 drug-na(?)ve adult patients with first-episode MDD with(A_MDD/SI+ group)or without SI(A_MDD/SI–group)and 35 healthy control subjects(A_HC group)underwent resting-state functional magnetic resonance imaging.The mean BOLD time course from bilateral habenula was extracted,and the Pearson’s correlation coefficients with the time course of all other voxels of the brain were calculated.Fisher’s r to z transformation was carried out to obtain the sFC map of habenula and the whole brain.Then,based on the sliding window correlation approach,the whole brain dFC maps for habenula were conducted between the averaged time course of all voxels in the seed and the time course of all other voxels in the whole brain.ANCOVA analysis was performed to identify regions showing significant difference among these three groups followed by region of interest to region of interest post hoc analysis.We also performed a Pearson partial correlation analysis with the score of the clinical psychological assessment scale to explore the correlation between these abnormal sFC/dFC and clinical symptoms.The part two included in 12 and 10 drug-na(?)ve adolescent patients with first-episode MDD with(a_MDD/SI+ group)or without SI(a_MDD/SI– group)and 14 healthy control subjects(a_HC group).All three groups underwent resting-state functional magnetic resonance imaging.The whole-brain habenula sFC and dFC were calculated to identify regions showing significant difference among these three groups followed by post hoc analysis.And Pearson partial correlation analysis was conducted to identify the dimensional correlations between clinical symptoms and neural patterns.Results:In the part one,for sFC,the results of ANCOVA analysis showed that there were abnormal sFC from the left habenula to the left putamen,left cerebellum and right precuneus,and from the right habenula to the right precuneus and left inferior frontal gyrus(P< 0.05,GRF correction).Compared with A_MDD/SI-and A_HC groups,A_MDD/SI+ group showed decreased sFC from right habenula to the right precuneus and the left inferior frontal gyrus(P< 0.05,Bonferroni correction).Adult patients with MDD displayed increased s FC from the left habenula to the left putamen but decreased s FC to the right precentral gyrus(P< 0.05,Bonferroni correction),regardless of SI.For dFC,the results of ANCOVA analysis showed that there were abnormal dFC from the left habenula to the right lingual gyrus,bilateral precuneus,and from the right habenula to the left superior temporal gyrus,left angular gyrus and left postcentral gyrus(P< 0.05,GRF correction).Compared with A_MDD/SI– and A_HC groups,A_MDD/SI+ group showed increased d FC from the left habenula to the left precuneus and from the right habenula to the left superior temporal gyrus,but decreased d FC from the left habenula to the lingual gyrus and from the right habenula to the postcentral gyrus(P< 0.05,Bonferroni correction).Adult patients with MDD,regardless of SI,displayed decreased dFC from the right habenula to the right angular gyrus(P> 0.05,Bonferroni correction).No correlation with the clinical symptoms were found(P> 0.05,Bonferroni correction).In the part two,for sFC,the results of ANCOVA analysis showed that there were abnormal sFC from the left habenula to the left precuneus,while from the right habenula to the left posterior cingulate gyrus and left middle cingulate gyrus(P < 0.05,GRF correction).Compared with a_MDD/SI-and a_HC groups,a_MDD/SI+ group showed decreased s FC from left habenula to the left precuneus and from the right habenula to the left posterior cingulate gyrus and left middle cingulate gyrus(P < 0.05,Bonferroni correction).For dFC,the results of ANCOVA analysis showed that there were abnormal d FC from the left habenula to the left middle cingulate gyrus and the right superior parietal gyrus,as well as from the right habenula to the left inferior frontal gyrus,left parietal inferior marginal angular gyrus,and right precentral gyrus(P < 0.05,GRF correction).Compared with a_MDD/SI- and a_HC groups,a_MDD/SI+ group showed decreased d FC from the left habenula to the left middle cingulate gyrus and from the right habenula to the right precentral gyrus,but increased dFC from the right habenula to the left inferior frontal gyrus(P<0.05,Bonferroni correction).Adolescent patients with MDD,regardless of SI,displayed increased dFC from the left habenula to the right superior parietal gyrus and from the right habenula to the left parietal inferior marginal angular gyrus(P<0.05,Bonferroni correction).No correlation with the clinical symptoms were found(P>0.05,Bonferroni correction).Conclusion:These findings provide evidence that SI in adult and adolescent patients with MDD may be related to an abnormality in habenula neural circuitry,from strength and stability aspects.Abnormal brain regions in adult patients were mainly involved in self-reference processing,response inhibition,emotional response,and introspective integration,while abnormal brain regions in adolescent patients were mainly involved in impulse regulation,cognitive control,and emotional response.Such finding may provide the theoretical basis of novel treatments.