Mitochondrial DNA Copy Number And Expression Levels Of Mitochondrial Quality Control Genes In Schizophrenia

Schizophrenia is a complex severe mental disorder,usually accompanied with serious recognition disorder,emotional loss and social disability.The prevalence rate of this disease is approximately 1%throughout the world.Schizophrenia is characterized with early onset,bringing heavy burden on the families and the whole society as the treatment costs a lot and difficult to cure.The exact etiology and pathogenesis of schizophrenia still remain unknown.Some hypotheses have been put forward to explain the cause of schizophrenia.Growing studies have reported the energy metabolism abnormality of schizophrenia and the role of mitochondrial dysfunction in it has attracted more and more attention.Mitochondria are the main place where the energy metabolism occurs in cells,responsible for the majority of energy supplement of human body.Mitochondrial dysfunction will influence the catabolism of energy substrates directly and cause energy supplement deficit.Therefore,exploration of mitochondrial dysfunction can provide great support in the pathogenesis of schizophrenia and to understand the role of metabolism abnormality in the pathogenesis of schizophrenia.Mitochondrial DNA(mt DNA)encodes proteins and RNAs vital for OXPHOS.mt DNA copy number is an important marker for mitochondrial content and integrity.The mitochondrial content dynamics is regulated by the quality control process,including bigenesis,mitophagy,fusion and fission.In this process,impaired mitochondria are degraded and new mitochondria are synthesized.This process is essential for mitochondrial normal functionIn this study,we measured mt DNA copy number and expression levels of mitochondrial quality control genes systematically.First,we detected mt DNA copy number in first episode drug-na?ve schizophrenia patients and healthy controls.And we found that mt DNA copy number reduced significantly in schizophrenia patients(P=0.000572,FC=-1.22).Then,we detected mt DNA copy number in schizophrenia patients under treatment in hospital.And we found that mt DNA copy number reduced significantly for 1.32 times after 4-week treatment(P=0.008),reduced for 1.19 times after another 4-week treatment(P=0.107)and increased for 1.38 times after long-term treatment(P=0.000012).Besides,we detected the expression levels of mitochondrial quality control genes in first episode drug-na?ve schizophrenia patients and healthy controls.And we found that in schizophrenia patients,in mitochondrial biogenesis,expression levels of SIRT1 and TFAM reduced significantly(P=0.044,FC=-1.08;P=0.029,FC=-1.17)and the expression level of NRF2 increased significantly(P=0.0009,FC=1.20);in mitophagy,expression levels of PINK1 and P62 increased significantly(P=0.003,FC=1.31;P=0.047,FC=1.10)and the expression level of PARK2 reduced significantly(P=0.044,FC=-1.16);in mitochondrial fusion,expression levels of MFN2 increased significantly(P=0.027,FC=1.21);expression levels of mitochondrial respiration chain complex I activity associated AIF and two mitochondrial genes MTATP8 and MTCO2 reduced significantly(P=0.0013,FC=-1.20;P=0.012,FC=-1.22;P=0.021,FC=-1.16).In this study,we measured mt DNA copy number and expression levels of mitochondrial quality control genes in schizophrenia patients and healthy controls.We found reduced mt DNA copy,down-regulated expression levels of mitochondrial biogenesis genes,up-regulated expression levels of mitophagy and fusion genes,and we concluded it to be abnormality of mitochondrial quality control mechanism in schizophrenia.This study led us know more about the changes of mitochondrial quality control in schizophrenia and provided evidences for the mitochondrial dysfunction hypothesis of schizophrenia,helping us understand the potential role of mitochondrial dysfunction in the etiology and pathogenesis of schizophrenia.