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Study On The Relationship Between Thealterations In Blood-Brain Barrier Permeabilityand Depression,Anxiety And Cognitive Impairment Insystemic Lupus Erythematosus

Posted on:2021-03-28Degree:MasterType:Thesis
Country:ChinaCandidate:Y L LuoFull Text:PDF
GTID:2404330605981110Subject:Internal Medicine
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Objective:Patients with systemic lupus erythematosus(SLE)are known as neuropsychiatric systemic lupus erythematosus(NPSLE)when their peripheral and central nervous systems are involved.Diffuse central nervous system involvement,such as depression,anxiety and cognitive impairment,is a common manifestation of NPSLE.The incidence of depression,anxiety and cognitive impairment is significantly higher in SLE patients than in the general population.At present,although the pathogenesis of NPSLE has not been fully elucidate,current studies have shown that blood brain barrier(BBB)injury is one of the pathogenesis of NPSLE.In this study,dynamic contrast enhanced MRI(dce-mri)was used to detect changes in BBB permeability in SLE patients,and to analyze the correlation between the brain regions and degree of alterations in BBB permeability and depression,anxiety,cognitive dysfunction and autoantibodies.Methods:1.We compared the BBB permeability indicator Ktrans value between SLE patients and healthy controls:Brain DCE-MRI images were collected from 42 SLE patients and 23 healthy controls,Based on the Patlak pharmacokinetic model,The Ktrans value of each voxel in the whole brain of each subject was calculated by a self-programmed method in Matlab 12,the Statistical Analysis of two independent samples was performed using the Statistical Analysis function of DPABI software(Cluster size=100,P?0.01 Statistically significant),at the same time,two groups of ktrans significantly different regions were output,extract the 3d image of this region,then calculate the Ktrans value of the whole brain of each subject and the Ktrans value of the regions with obvious differences.Finally,the non parametric test of Mann Whitney U test was used to compare the Ktrans of BBBpermeability indicatorbetween SLE patients and healthy control group.2.Correlation analysis of BBB permeability indicator with depression,anxiety and cognitive dysfunction in patients with SLE:Adopt the static analysis function of dpabi software,add age and gender as covariates,Partial correlation analysis was made between Ktrans and HAMD,HAMA and MMSE scales.The result is presented by the Viewer in the DPABI software.3.The potential relationship between depression,anxiety and cognitive dysfunction and CSF autoantibody in SLE patients:HAMD scale result,HAMA scale result and MMSE scale result were used as dependent variables,the cerebrospinal fluid autoantibodies,including anti dsDNA antibody,anti ssa-52 antibody,anti ssa-60 antibody,anti SSB antibody,anti lupus Anti-? 2-glycoprotein I antibody and anti U1 RNP antibody,were used as independent variables,conduct multiple linear regression analysis.Results:1.Comparison of BBBpermeability indicatorbetween SLE patients and healthy controls:Using the statistical analysis function of dpabi software to do independent sample t-test to compare the brain volume transfer constant Ktrans images of 42 SLE patients and 23 healthy controls(Cluster size=100,P=0.01).The results showed that the Ktrans in the right insula of the patients increased significantly.Further extraction of three-dimensional images of the whole brain and right insula,the average value of Ktrans in the whole brain and the right insula of the patients and the control group were calculated,use nonparametric test to compare the difference between patients group and healthy control group.The results showed that the Ktrans value of the right insula area in the SLE patients group was significantly higher than that in the healthy control group,the difference was statistically significant(P<0.05).However,there was no significant difference between the SLE patients group and the healthy control group.2.Correlation analysis of BBB permeability indicator with depression,anxiety and cognitive dysfunction in patients with SLE:2.1 Partial correlation analysis was made between the scores of HAMD and the Ktrans value of the whole brain in 42 SLE patients,gender and age as covariates.The results showed that there was a positive correlation between HAMD scale result and Ktrans value in the left dorsolateral superior frontal gyrus and the left paracentral lobule of the left brain in 42 SLE patients(r=0.59169,P=0.005).That is to say,the more serious the depressive symptoms of SLE patients,the higher the Ktrans value of the left dorsolateral superior frontal gyrus and the left paracentral lobule area2.2Partial correlation analysis between HAMA scale score and Ktrans value of brain voxels,gender and age as covariates,The results showed that there was a positive correlation between HAMA score result and Ktrans value in theright orbital inferior frontal gyrus region of SLE patients(r=0.5616,P=0.005),In other words,the more severe the anxiety symptoms in SLE patients,the higher the ktrans value in the inferior frontal gyrus region of the right orbital part of the brain2.3 Partial correlation analysis between MMSE scale score and Ktrans value of brain voxels,gender and age as covariates.The results showed that there was a negative correlation between MMSE scale score and Ktrans value of right inferior temporal gyrus in SLE patients(r=-0.53719,P=0.005).That is to say,the more severe the degree of cognitive dysfunction in SLE patients,the higher the Ktrans value in the right inferior temporal gyrus.3.Study on the potential relationship between depression,anxiety and cognitive dysfunction and CSF autoantibody in SLE patients:Multiple linear regression analysis was performed with HAMD score,HAMA score and MMSE score as dependent variables and CSF autoantibodies,including anti dsDNA antibody,anti ssa-52 antibody,anti ssa-60 antibody,anti SSB antibody,Anti-? 2-glycoprotein ?antibody and anti U1 RNP antibody as independent variables.3.1 HAMD score of SLE patient correlated with anti ssa-60 antibody in CSF,The HAMD scale score of SLE patients with positive CSF anti ssa-60 antibody was higher That is to say,the more severe the depressive symptoms of SLE patients with positive CSF anti ssa-60 antibody are.3.2 There is no correlation between HAMA score and CSF autoantibody in SLE patients.3.3 MMSE scale score of SLE patients is related to CSF anti SSB antibody.The MMSE sacle score of SLE patients with CSF anti SSB antibody positive is lower,that is to say,the cognitive dysfunction of SLE patients with CSF anti SSB antibody positive is more serious.Conclusions:This study confirmed that there has alterations in BBB Permeabilityin SLE patients,which is mainly located in the right insula area.The increase of BBB permeability in some brain areas of SLE patients may be related to some neuropsychiatric disorders.The increase of BBB permeability in the left dorsolateral superior frontal gyrus and left paracentral lobule may be related to depression,the increase of BBB permeability in the right orbital inferior frontal gyrus may be related to anxiety,and the increase of BBB permeability in the right temporal inferior gyrus may be related to cognitive impairment.Increased BBB permeability may be one of the mechanisms leading to the emergence of autoantibodies in CSF,among which CSF anti-SSA-60KD antibody and anti-SSB antibody may be related to depressive symptoms and cognitive impairment in SLE patients,respectively.
Keywords/Search Tags:systemic lupus erythematosus, Blood-brainbarrier, Depression, Anxiety, Cognitive impairment
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