Changes Of Mitophagy And Inflammasome Related Genes In Depression Patients Before And After Electroconvulsive Therapy

Objective:To explore the underlying pathogenesis of depression by comparing the difference of levels of mitophagy-associated genes,inflammasome-related genes and serum inflammatory factors in lymphocytes between severe depression group and normal control group.To explore the potential mechanism of anti-depression effect of modified electroconvulsive therapy by comparing the difference of relative genes and serum inflammatory factors levels before and after modified electroconvulsive therapy in patients with severe depression.Methods:Totally 32 subjects who meet the criteria for the diagnosis of severe depression,as defined in International Classification of diseases10（ICD-10）,with a Hamilton Depression Scale（HAMD-17）≥24 points,30 to 65 years of age,were included in compliance with the modified electroconvulsive therapy.19 healthy volunteers were enrolled as normal control group.The scale and the peripheral blood were collected before and 7 days after the treatment with modified electroconvulsive therapy.Reverse Transcription Polymerase Chain Reaction（RT-PCR）method and enzyme-linked immunosorbent assay（ELISA）were used to compare the Differences of mitophagy-associated genes,inflammasome-associated genes and serum inflammatory factors in lymphocytes between the severe depression group and the normal control group,between the severe depression group before and after the Modified electroconvulsive therapy.Results:1.In this study,32 patients with severe depression were included as the severe depression group.All patients completed the treatment of modified electroconvulsive treatment（6 to12 times）and were collected blood samples,estimated scales.There were no significant differences in age,sex,smoking and drinking history,body mass index and years of education between severe depression group and normal control group.The scores of HAMD,Hamilton Anxiety Scale（HAMA）and Beck Suicide Ideation Scale（SSI）after treatment with modified electroconvulsive therapy were significantly lower than those before treatment（t=23.317,P=0.000;t=5.867,P=0.000;t=5.553,P=0.000）.There was a significant difference between the two groups.2.The mitophagy-associated genes,inflammasome-associated genes and serum inflammatory factors in patients with severe depression were compared with those in normal controls:（1）The Cycle threshold（C_T）of PCR were processed according to 2^-△△CTmethod.The median mitophagy-related genes relative expression levels of PINK1（PTEN induced putative kinase 1 gene）,BECN-1,NLRP3 and ASC（Apoptosis-associated Speck-like gene containing a CARD）mRNA in severe depression group were 0.378,0.464,4.503 and 2.903,respectively.The median relative expression levels of PINK1,BECN-1,NLRP3 and ASC mRNA were 1 in normal control group.A statistical analysis of the normal control group and the severe depression group was performed using two independent samples,Mann-Whitney U test.The results showed that the expression of PINK1 and BECN-1 of the patients with severe depression was significantly lower than that of the normal control group（Mann-Whitney U=85.500,P<0.001;Mann-Whitney U=126,P<0.01）.The expression of NLRP3 and ASC mRNA was significantly higher than that of the control group（Mann-Whitney U=23,P<0.001;Mann-Whitney U=126,P<0.001）.（2）The median values of interleukin-1（IL-1）,tumor necrosis factor（TNF-α）,interleukin-6（IL-6）and C-reactive protein （CRP） in normal control group were 110.700ng/L,722.900ng/L,40.110ng/L and 53.700ug/L respectively.The median values of IL-1,TNF-α,IL-6 and CRP in severe depression group were 234.900ng/L,569.900ng/L,23.950ng/L and 46.270ug/L respectively.There was no significant difference in IL-6,TNF-αand CRP between the two groups（Mann-Whitney U=192,P=0.054;Mann-Whitney U=259,P=0.565;Mann-WhitneyU=261.500,P=0.599）.The level of IL-1 in the severe depression group was significantly higher than that in the normal control group（Mann-Whitney U=138,P=0.001）.（3）There was a significant correlation between the relative expression of PINK1 mRNA and IL-1（r_s=-0.845;P<0.001）,and between the relative expression of BECN-1 mRNA and IL-1（r_s=-0.565;P<0.001）in patients with severe depression.3.The mitophagy-associated genes,inflammasome-associated genes and serum inflammatory factors in patients with severe depression were compared before and after the treatment with modified electroconvulsions:（1）The C_T of PCR were processed according to 2^-△△CT△△CT method.Before the modified electroconvulsive treatment,the median expression levels of PINK1,BECN-1,NLRP3 and ASC mRNA in the group of patients with severe depression （before modified electroconvulsions） were 1,and the median values of the expression levels of PINK1,BECN-1,NLRP3 and ASC mRNA were 2.321,3.095,0.829 and 0.196 in the patients with severe depression after modified electroconvulsive therapy,respectively.Two related samples Wilcoxon signed rank sum test were used between the two groups matched before and after modified electroconvulsions.The expression level of PINK1mRNA in severe depression group after modified electroconvulsive therapy was significantly higher than that before（P=0.002）.The expression level of BECN-1 mRNA in severe depression group after modified electroconvulsive therapy was significantly higher than that before（P=0.033）,the expression level of ASC mRNA was significantly lower than that before（P=0.011）.There was no significant difference in the expression of NLRP3 mRNA between before and after treatment（P=0.705）.（2）The level of IL-1 in patients with severe depression after modified electroconvulsive therapy was significantly lower than that before treatment（P<0.001）.There was no significant difference in the levels of IL-6,TNF-αand CRP between before and after treatment（P=0.449,P=0.859,P=0.385）.Conclusions:1.The inhibition of mitophagy level and the activation of inflammasome may involve in the pathogenesis of major depressive disorder,mitophagy is closely related to the activation of inflammasome.2.Modified electroconvulsive therapy has a positive effective antidepressant effect,and the modified electroconvulsive therapy may achieve the antidepressant effect by activating mitophagy and anti-inflammation.