Study Of Bipolar Disorder And Major Depressive Disorder During Depressive State On Resting-state Functional Magnetic Resonance Imaging And Correlation With Brain-derived Neurotrophic Factor

Objective: Bipolar disorder(BD)and major depressive disorder(MDD)are two common clinical mental disorders,characterized of high recurrence rate,high disability rate and heavy disease burden.They are ranked the top in the world disease burden ranking.When BD is in the stage of depressive episode,that is,bipolar disorder in depressive state(BDD),it has a very similar clinical manifestation compared to MDD,which is very easy to cause misdiagnosis,inappropriate drug therapy,thus cause a worse prognosis,severe social dysfunction and heavy burden of disease.At present,the diagnosis of mental illness mainly depends on the psychiatric interview or interrogation by the clinician for the patients and their relatives,then the diagnosis is made according to the mental disease diagnosis system combined with the clinical assessment scale,while the objective biological basis is lacking in supporting the correctness of the diagnosis.Resting state functional magnetic resonance(f MRI)has been widely used in the study of the pathophysiological mechanism of mental disease.However,few studies directly compared between BDD and MDD,which were single algorithms,and the results were not consistent.So,it is necessary to conduct an intensive study.And,the study of the correlation between the resting state functional magnetic resonance(f MRI)of BDD,MDD and the brain-derived neurotrophic factor(BDNF)protein level has not been reported.We aimed to use the method of combining Re Ho with ALFF for the first time,to compare the imaging differences between BDD and MDD;and used the methods of of voxel-based correlation analysis to study the correlation of Re Ho,ALFF and BDNF to explore the similarities and differences of pathophysiological mechanisms of the two diseases from the perspective of imaging and molecular biology,so as to provide an objective biological basis for the accurate diagnosis and correct treatment of the two mental diseases and provide supports for further improving the diagnostic system of mental illness.Methods: Patients with BDD and MDD were diagnosed according to the diagnostic criteria of the American Psychiatric Disorders Diagnostic and Statistical Manual Fourth Edition(DSM-IV)and through structured clinical interview(SCID)or semi fixed diagnostic examination manual for children and adolescents(K-SADS-PL),then GE 3.0T magnetic resonance scanner was used to perform resting state functional magnetic resonance imaging(f MRI)scan.Then the HAMilton Depression scale-17 items(HAMD-17)was evaluated.And telephone follow-up method was used to track whether MDD patients had manic episodes,and further determined whether the diagnosis should be changed to BDD.Demographic data and clinical information of 20 BDD,31 MDD and 63 healthy controls(HC)who were eligible for inclusion criteria were analyzed by SPSS22.0 software package.The steps of comparison of functional imaging data and their correlation with BDNF were as follows: 1.DPABI V2.1 software package was used to preprocess the imaging data and analyze Re Ho and ALFF data.Analysis of covariance(ANCOVA)was used to compare the difference of Re Ho and ALFF value across the three groups(age and sex as covariate),and two-sample t test were carried out after the post hoc t test.2.All the subjects were demanded to collect the elbow vein blood and the plasma was frozen.And the level of BDNF protein was detected by the method of Luminex,one multi factor detection technique.The correlation analysis was analyzed between the Re Ho and ALFF values of the BDD and MDD groups in the differential brain regions of ANCOVA results and BDNF.Then the correlation of Re Ho,ALFF of BDD and MDD patients and BDNF protein level was analyzed by the method of voxel-based correlation analysis in the whole brain.Results: 1.ANCOVA results of Re Ho values across the three groups showed that there was one significant difference brain region: cluster1(CL1): right hippocampus,amygdala,parahippocampal gyrus,right middle temporal pole,right superior temporal pole,right orbital inferior frontal gyrus,and significant differences were found in the above regions(p<0.001).After the post hoc two-sample t test,Re Ho value of BDD was found significantly lower in the right hippocampus,amygdala,parahippocampal gyrus,right orbital inferior frontal gyrus compared to HC;Re Ho value of BDD in the right hippocampus,amygdala,parahippocampal gyrus,right middle temporal pole,superior temporal pole,right orbital inferior frontal gyrus was significantly lower compared to MDD.2.ANCOVA results of ALFF values across the three groups showed significant differences in two clusters,Cl1: right caudate nucleus,hippocampus,parahippocampal gyrus,amygdala,olfactory cortex,anterior cingulate gyrus,putamen,right fusiform gyrus and rectus gyrus(p<0.001);Cl2: left postcentral gyrus,superior temporal gyrus,left rolandic operculum,precentral gyrus,left insula,left Heschl gyrus,middle temporal gyrus.After the post hoc two sample t test,it was found that the ALFF values of BDD were lower in left superior temporal gyrus and left insula compared to HC(p<0.001).The ALFF values of MDD in the right parahippocampal gyrus,hippocampus,caudate nucleus,putamen,right olfactory cortex,anterior cingulate gyrus and right rectus gyrus were higher compared to HC.Compared to HC,MDD has a lower ALFF value in the left postcentral gyrus,left superior temporal gyrus,precentral gyrus,rolandic operculum;left superior temporal gyrus,left insula and left Heschl gyrus.Compared to MDD,the ALFF values of the right hippocampus,caudate nucleus,amygdala,parahippocampal gyrus,anterior cingulate gyrus and right olfactory cortex were decreased in BDD.3.Both Re Ho and ALFF values of BDD were lower than MDD in the right hippocampus,amygdala and parahippocampal gyrus.4.In BDD and MDD group,there was no correlation between the Re Ho and ALFF values in the differential brain regions of ANCOVA results and the level of BDNF protein.There was no correlation between the Re Ho and the level of BDNF protein in BDD and MDD group using the method of voxel-based correlation analysis.Using the method of voxel-based correlation analysis,the ALFF values of BDD group were correlated with the level of BDNF protein and two related brain regions were obtained,cluster 1: Right parahippocampal gyrus,right middle temporal pole,right fusiform gyrus;cluster 2: bilateral rectus gyrus,left orbital superior frontal gyrus.Using the method of voxel-based correlation analysis,the ALFF values of MDD group were correlated with the level of BDNF protein,and three related brain regions were obtained,cluster 1: left parahippocampal gyrus,left fusiform gyrus,and left hippocampus;cluster 2: right calcarine,right parahippocampal gyrus,right precuneus,right lingual gyrus;cluster 3: left fusiform gyrus,left lingual gyrus.Conclusion: 1.There are differences and commonalities between the pathophysiological basis of BDD and MDD.2.Changes of the spontaneous activity in the right parahippocampal gyrus,rectus gyrus and right fusiform gyrus might contribute to the pathophysiology of BDD;changes of spontaneous activity in the right parahippocampal gyrus might contribute to the pathophysiology of MDD;changes of spontaneous activity in the right parahippocampal gyrus might be a common factor in the pathophysiological process of BDD and MDD in the state of depression.