The Correlation Between Gray Matter Volume Abnormity In Prefrontal Cortex And Plasma Glial Cell Line-Derived Neurotrophic Factor Levels Within Major Depressive Disorder

Objective: Major depressive disorder(MDD)is a severe mental disorder characterized by reduced gray matter volume(GMV).To date,the pathogenesis of MDD remains unclear,but neurotrophic factor plays an essential role in the pathophysiological alterations of MDD during disease development.In particular,plasma glial cell line-derived neurotrophic factor(GDNF)has been suggested as a potential biomarker that may be associated with disease activity and neurological progression in MDD.Our study investigated whether GMV alterations in the brain of MDD correlate with plasma GDNF levels in order to investigate whether the imaging features are associated with neurobiological mechanisms in MDD.Methods: The study totally recruited 136 subjects,whose ages ranged from 18 to 45 years,right-handedness,including 71 patients with MDD and 65 age-,sex-and education matched healthy control(HC).First,all participants are informed of the overall process and content of the study,then they sign an informed consent form voluntarily and the demographic data is collected.In addition,the diagnosis of MDD was confirmed by Structured Clinical Interview for DSM-IV(SCID),and clinical characteristics were quantified by the 17-item Hamilton depression rating scale(HAMD-17)and Hamilton anxiety rating scale(HAMA).Meanwhile,blood samples were collected and processed to obtain plasma GDNF data,and structural magnetic resonance imaging(s MRI)scans were performed to obtain brain GMV images.Secondly,the demographic information,clinical data and GDNF data were statistically analyzed in SPSS(Statistical Product and Service Solutions)software,using chi-square test,independent samples t-test,two-factor factorial design Analysis of Variance(ANOVA)(Bonferroni correction)for the subsequent correlation analysis.Software packages and toolkits based on the Matlab platform were used for the pre-processing and statistical analysis of image data to compare the differences between the MDD patient group and the HC group,and to extract GMV values that showed differential brain regions between the above two groups.Finally,SPSS software was used to analyze whether the GMV values extracted from the differential brain regions in the MDD group correlated with plasma GDNF levels.Results: 1.Compared to the HC group,a significant decrease of GMV values was found in the MDD group(t=5.610,p<0.0001)at the right orbitofrontal cortex(OFC)(AAL90,MNI coordinates: x=45,y=48,z=-4.5;voxel size: 1248;t-value: 3.635;p<0.05(Gaussian random field(GRF)correction);There was a significant difference in brain GMV values between different diagnoses(F=17.879,p<0.0001,Bonferroni correction),but no significant difference in brain GMV values between different genders(F=0.833,p=0.363,Bonferroni correction).We also found that ‘diagnosis × gender’ had no interaction effect on brain GMV(F=3.004,p=0.085,Bonferroni correction);In the MDD group,there was no significant difference in brain GMV values between the first-onset and relapsed MDD groups,the drug-used and drug-naive MDD groups.2.Plasma GDNF levels were significantly higher in the MDD group compared to the HC group(t=-3.261,p=0.0014);There was a significant difference in plasma GDNF levels among different diagnoses(HC and MDD)(F=7.554,p=0.007,Bonferroni correction).However,there was no significant difference in plasma GDNF between male and female(F=1.091,p=0.298,Bonferroni correction).We also found that ‘diagnosis × gender’ had no interaction effect on plasma GDNF levels(F=0.172,p=0.679,Bonferroni correction).Within the MDD group,plasma GDNF levels did not significantly differ between the first-onset and relapsed,the drugused and drug-naive groups;3.GMV values in the MDD group did not correlate significantly with age,years of education,disease duration,HAMD-17 or HAMA;while in the HC group,there was no significant correlation between GMV values and age;plasma GDNF levels in all MDD patients were not significantly correlated with age,years of education,disease duration,HAMD-17,HAMA,and similarly,in the HC group,plasma GDNF levels were not significantly correlated with age.At the right OFC,a positive correlation was found between GMV values and GDNF levels in the MDD group(r=0.307,p=0.009),while no significant correlation was found between the two in the HC group(r=-0.236,p=0.059).Conclusion: 1.GMV at the right OFC of the brain was significantly reduced in MDD patients,suggesting that MDD patients have structural abnormalities of the brain at the right OFC;2.Plasma GDNF levels were significantly increased in MDD patients,suggesting that GDNF may be a potential biomarker in the disease process of MDD;3.GMV values at the right OFC of the brain was positively correlated with plasma GDNF levels in MDD patients,suggesting that the brain structure of MDD patients is associated with plasma GDNF,and GDNF may be involved in the pathophysiological process of MDD disease.