Association Study Of Catechol-O-methyltransferase Val158Met Polymorphism And Resting-state Functional Connectivity Between The Amygdala And Prefrontal Cortex In Major Depressive Disorder

Objective Major depressive disorder(MDD)is one of the common mental disorders and has a high prevalence of relapse,disability and suicide.Studies have shown that the pathogenesis of MDD may be related to the low function of the dopamine system in the central nervous system.COMT gene plays a key role in the regulation of dopamine metabolism in the central nervous system.At the same time,studies have shown that COMT Val158 Met gene polymorphism is associated with the onset of Major Depression Disorder(MDD),but the specific mechanism has not been clarified.This study applies gene imaging technology to investigate effects of the COMT gene polymorphism(rs4680)on resting-state brain function of major depressive disorder.Methods We recruited 59 patients with MDD and 66 healthy control through strict inclusion and exclusion criteria.All subjects were divided into a GG group homozygous for the V allele(n = 64)and a A-carrier group(GA/AA genotypes,n =61).All subjects participated resting-state functional magnetic resonance imaging(rs-f MRI)scans.Functional connectivity analyses were performed.Results(1)There was no significant difference in demographic data(including age,gender and years of education)between MDD patients and HC(P>0.05),and there is a significant difference in HAMD-17 score(P<0.001).The genotypes and allele frequencies of all subjects were consistent with the Hardy-Weinberg distribution.(2)Left amygdala as ROI:There was a significant diagnostic main effect in Frontal_Mid_R(aal).MDD patients showed lower FC value than HC(P<0.005,GRF correction)(3)Left amygdala as ROI:significant COMT gene main effect was found in Frontal_Sup_R(aal),where subjects with A allele showed higher FC value than those with GG genotype.(4)Left amygdala as ROI:There was significant COMT genotype diagnostic interaction in Frontal_Inf_L(aal),the FC value increased in MDD with GG genotype(P<0.005,GRF correction);(5)Right amygdala as ROI: no significant diagnostic main effect,COMT gene main effect or COMT genotype diagnostic interaction were found.Conclusion COMT Val158 Met gene polymorphism affects functional connectivity between amygdala and prefrontal in MDD patients.The study indicates that COMT gene variation may be associated with neuropathophysiology and pathogenesis of MDD.