Regional Homogeneity Of Brain Rest State Function In Patients With First-episode Untreated Major Depressive Disorder Treated With Vortioxetine For 12 Weeks

Objectives:Regional Homogeneity(ReHo)technique of Resting-state functional magnetic resonance imaging(rs-fMRI)was used to study:1.the difference of brain function between the patients with untreated major depressive disorder(MDD)and the healthy control(HC)group at the time point of baseline,2 weeks and 12 weeks of treatment.2.the changes of brain function in patients with MDD treated with vortioxetine(VOR)for 2 weeks and 12 weeks,and the neural mechanism of VOR in improving depressive symptoms and cognitive function.Methods:A total of 39 patients who met the criteria of MDD in the fourth edition of the American Diagnostic and Statistical Manual of Mental Disorders(DSM-?)were recruited and treated with VOR.Hamilton Depression scale(HAMD-17),Repeatable Battery for the Assessment of Neuropsychological Status(RBANS)and rs-fMRI were measured at baseline and 2 weeks and 12 weeks after treatment.At the same time,12 healthy controls were evaluated by HAMD-17,RBANS and head rs-fMRI scan.The DPABI software package based on MATLABR2016a software platform was used to preprocess the magnetic resonance data,and the ReHo brain map was obtained.The images of the MDD group and the HC group were tested by independent sample t-test,and the images of the MDD group before and after treatment with VOR were analyzed by one-way repeated measurement analysis of variance,and then pairwise comparisons were made.The correlation between the changes of brain function and clinical symptoms in the MDD group before treatment was analyzed.The results were presented by RESTplus software.Results:1.The basic information in MDD group:There were 39 cases in the MDD group before treatment,including 5 cases with unqualified data and 34 cases with the rest.After 2 weeks of treatment,6 cases were lost,5 cases were not scanned by rs-fMRI,and 28 cases were left behind.After 12 weeks of treatment,6 cases were lost,4 cases were not scanned by rs-fMRI,and 23 cases were left behind.Among them,19 cases completed the whole study process,5 cases were excluded for unqualified data,and the remaining 14 cases.2.Comparison between the baselin of MDD group(n=34)and the HC group:There were significant differences in the total scores of HAMD-17 and RBANS between the two groups.The total scores of HAMD-17 and RBANS in the MDD group were significantly lower than those in the HC group.ReHo values of right inferior cerebellum,temporal pole:superior temporal gyrus,left hippocampus and parahippocampal gyrus/fusiform gyrus/inferior cerebellum increased,while ReHo values of right middle occipital gyrus/calcarine cortex/cuneus,fusiform gyrus,superior occipital gyrus,left middle occipital gyrus and calcarine cortex/superior occipital gyrus/fusiform gyrus/cuneus,decreased.3.Comparison between the MDD group and the HC group after 2 and 12 weeks of treatment with VOR:After two weeks VOR treatment,there were significant differences in the total scores of HAMD-17 and RBANS between the MDD group(n=28)and the HC group.However,the gap in the total scale of HAMD-17 between the two groups is narrowing.The brain regions with significant differences between the two groups were reduced,but there were still differences between the two groups.ReHo values of the right fusiform gyrus,left superior temporal gyrus,parahippocampal gyrus,triangular inferior frontal gyrus,inferior parietal marginal angular gyrus/supramarginal gyrus increased.In contrast,ReHo values of right middle occipital gyrus,cuneus,inferior cerebellum,left middle occipital gyrus and supplement motor area decreasedTwelve weeks after treatment,there was still a significant difference in the total score of HAMD-17 between the MDD group(n=23)and the HC group(p<0.05).However,the gap in the total score of HAMD-17 between the two groups was further narrowed.There was no significant difference in the total score of RBANS between the two groups.The brain regions with significant differences between the two groups were further reduced,and there were only differences between the two groups.The ReHo values of the right fusiform gyrus,superior temporal gyrus/transverse temporal gyrus,left inferior cerebellum and inferior temporal gyrus increased,while ReHo values of left middle occipital gyrus decreased.4.Comparison within the MDD group(n=14):There were significant differences in the total score of HAMD-17 and RBANS at three-time points.The HAMD-17 total score after 2 weeks of treatment was significantly lower than that before treatment,and the total score after 12 weeks of treatment was significantly lower than that before treatment and 2 weeks after treatment.There was no significant difference in the RBANS total score between 2 weeks after treatment and before treatment,but there was significant difference between 12 weeks after treatment and before treatment and 2 weeks after treatment.There were significant differences in brain regions at three-time points:left inferior temporal gyrus,superior cerebellum,superior temporal gyrus,middle frontal gyrus/dorsolateral superior frontal gyrus,inferior parietal marginal angular gyrus/supramarginal gyrus,right superior cerebellum,inferior temporal gyrus,caudate nucleus,superior temporal gyrus/supramarginal gyrus,postcentral gyrus.The ReHo value of the right caudate nucleus at 2 weeks after treatment was significantly lower than that before treatment.After 12 weeks of treatment,compared with 2 weeks of treatment,the ReHo value of left middle frontal gyrus/dorsolateral prefrontal lobe and left inferior parietal marginal angular gyrus/supramarginal gyrus decreased significantly,while the ReHo value of right postcentral gyrus increased.5.Correlation:At baseline,in MDD group(n=34),the whole brain ReHo value was positively correlated with HAMD-17 score:right hippocampus,parahippocampal gyrus,fusiform gyrus,putamen,cuneus,left olfactory cortex,anterior cingulate gyrus,and negatively correlated brain regions:right postcentral gyrus,precentral gyrus,angular gyrus,left supplement motor area,middle temporal gyrus,paracenter lobule.Before treatment,in MDD group(n=34),the whole brain Reho value was positively correlated with the total score of RBANS:right postcentral gyrus,lingual gyrus,and negatively correlated brain areas:right hippocampus,insular,left thalamus,middle frontal gyrus,inferior parietal angular gyrus,rectus gyrus.Conclusions:1.Compared with the HC group,there were functional abnormal brain regions in the baseline stage,including occipital lobe,temporal lobe,cerebellum and so on,suggesting that there may be extensive brain dysfunction in patients with MDD.2.VOR can effectively improve the depressive symptoms and cognitive function of patients with MDD.3.After treatment,the functional abnormal brain areas in the MDD group gradually decreased,suggesting that VOR could reverse the abnormal brain regions of the patients.4.VOR may improve depressive symptoms by regulating the function of striatum(right caudate nucleus),improve cognitive function and continuously improve depression by regulating the function of dorsolateral prefrontal cortex(left middle frontal gyrus/dorsolateral superior frontal gyrus)and parietal cortex(left inferior parietal angular gyrus/supramarginal gyrus,right postcentral gyrus).