The Study Of The Relationship Between SIRT1 Gene And Brain White Matter Neural Network In First Onset Untreated Adolescent Major Depressive Disorder

?Objectives?In recent years,studies have found that the silent information regulator 1(SIRT1)gene is related to the neuropathic mechanism of major depressive disorder(MDD).At the same time,many studies on MDD have also found that a large number of white matter fiber tracts in patients with MDD have microstructural changes,but the relationship between SIRT1 gene and brain white matter structure in patients with MDD is unclear.In this study,the first onset untreated adolescent MDD group was selected to explore the relationship between the SIRT1 gene(rs12415800)single nucleotide polymorphism(SNP)and the white matter neural circuit of MDD.?Methods?This study have 119 subjects,including 59 cases of adolescents with MDD as the MDD group,and 60 healthy volunteers matching age,gender and education level were selected as the control group.All subjects underwent magnetic resonance diffusion tensor imaging(DTI)and blood samples were taken for genotyping.Genotyping results showed that SIRT1 gene rs12415800 locus contained three genotypes: GG,GA and AA.According to whether the genotype carried A risk allele,the MDD group and the control group were divided into four groups: the MDD(GG)group,the MDD(AG/AA)group,the control(GG)group and the control(AG/AA)group.The DTI data was processed using tract-based spatial statistics(TBSS)to obtain fractional anisotropy(FA).The independent sample t-test was used to compare the FA values between the MDD group and the control group.The FA values of the fiber tract regions with statistical difference was extracted in the MDD group,and the correlation analysis was performed between FA values and center for epidemiological studies depression scale(CES-D)scores,the 9-item Patient Health Questionnaire(PHQ-9)scores and the course of the disease.The data of the MDD(GG)group,the MDD(AG/AA)group,the control(GG)group and the control(AG/AA)group were divided into two factors which are diagnosis and genotype,and each factor has two levels: diagnosis(MDD and health)and genotype(AG/AA and GG).2×2 two-way ANOVA analysis was performed to compare the FA values of the four groups to obtain their respective main effect and the diagnosis and genotype interaction effect.The results were corrected for multiple comparison correction using Threshold-Free Cluster Enhancement(TFCE)method,and the differences in the CES-D scores?PHQ-9 scores and course of the disease between the MDD(GG)group and the MDD(AG/AA)group were also compared.?Results?1.Compared with the control group,the MDD group had decreased FA values in the left anterior thalamus radiation and the left corticospinal tract(P <0.05,TFCE).The FA values of significant different fiber tract regions were not significantly correlation with CES-D scores(r =-0.076,P = 0.503),PHQ-9 scores(r =-0.099,P = 0.375)and disease course(r =-0.16,P = 0.885).2.Diagnosis and gene interaction effect results showed that there was a statistical difference in the FA values of the regions in the left cingulate fasciculus and the left anterior thalamic radiation.In the above regions,it was found that when the genotype was AG/AA,compared with the genotype of GG,the FA value of the MDD group decreased more than the control group,and the FA values of the MDD(AG/AA)group decreased the most.3.Genotype main effect results showed the FA values of the regions in the right inferior occipital-frontal fasciculus,the right corticospinal tract,the right inferior longitudinal fasciculus and the right superior longitudinal fasciculus regions were statistically different.In the above regions,the FA values of the MDD(AG/AA)group was decreased compared with the MDD(GG)group,and the control(AG/AA)group showed lower FA values than the control(GG)group.4.Diagnosis main effect results showed the FA values of the right inferior occipital-frontal fasciculus,the left corticospinal tract,the right inferior longitudinal fasciculus,the left anterior thalamus radiation,the right superior longitudinal fasciculus,the left inferior longitudinal fasciculus,the left uncinate fasciculus and the right anterior thalamus radiation were statistically different.In the above regions,the MDD(GG)group compared with the control(GG)group had decreased FA values,and compared with the control(AG/AA)group,the MDD(AG/AA)group showed lower FA values.5.Compared with the MDD(GG)group,the MDD(AG/AA)group had a longer course of disease(t =-2.16,P = 0.034).CES-D scores(t = 1.636,P = 0.106)and PHQ-9 scores(t = 0.265,P = 0.792)between the MDD(GG)group and the MDD(AG/AA)group were not statistically different.?Conclusions?1.The adolescents with MDD may have damage to the microstructure of white matter fiber tracts in the left corticospinal tract and the left anterior thalamus radiation than the healthy adolescents.2.The SIRT1 gene rs12415800 locus single nucleotide polymorphism and MDD both affect the adolescent brain white matter fiber tract microstructure.The two factors interact with each other and may cause greater damage to the white matter fiber tract microstructure of the adolescents with MDD who carry the A allele(AG/AA)in the left cingulate fasciculus and the left anterior thalamus radiation regions.3.When the diagnostic factors are the same(MDD or normal),compared with not carrying A allele(GG),carrying A allele(AG/AA)may cause more damage to the brain white matter fiber tract microstructure in the right inferior occipital-frontal fasciculus,the right corticospinal tract,the right inferior longitudinal fasciculus and the right superior longitudinal fasciculus regions.4.When the adolescent patients with MDD and healthy adolescents carry the same genotype(AG / AA or GG),there may be damage to the microstructure of white matter fiber tracts of adolescent patients with MDD than healthy adolescents in the right inferior occipital-frontal fasciculus,the left corticospinal tract,the right inferior longitudinal fasciculus,the left anterior thalamus radiation,the right superior longitudinal fasciculus,the left inferior longitudinal fasciculus,the left uncinate fasciculus and the right anterior thalamus radiation regions.5.The microstructure of white matter fiber tracts of the adolescents with MDD who carry the A allele(AG/AA),compared those who do not carry the A allele(GG),may be damaged for a longer period of time.In summary,this study not only found that there may be abnormal changes in the microstructure of the white matter neural network fiber tracts in adolescent patients with MDD,but also found that SIRT1 gene rs12415800 locus single nucleotide polymorphism may also affect the microstructure of white matter fiber tracts in adolescent with MDD.The microstructure of the white matter neural network fiber tracts in adolescent patients with MDD carrying A allele may undergo more damage.Those fiber tracts are widely and directly used as mediators of neural information transmission in cognitive functions,emotional regulation functions and executive functions,the microstructure damage of which may alter or disrupt neural network functions,and finally may affect cognitive and emotional regulation in adolescents with MDD.