The Role Of Glu/GABA-Gln Metabolic Circuit In Pathological Mechanisms Of Major Depressive Disorder,Bipolar Depressive Disorder And Insomnia Disorder

Objective:To explore whether the abnormity of Glu/GABA-Gln metabolic circuit is related to the pathological mechanism of MDD,BDD and insomnia disorder,and whether it is the common pathological mechanism of the three disorders?Methods:A total of 47 patients with MDD,34 patients with BDD,30 patients with insomnia disorder who met the corresponding diagnostic criteria of DSM-5 and30 healthy controls were recruited in the study,and conducted structured clinical interviews with International Neuropsychiatric Disorder interviews.Mood Disorder Questionnaire(MDQ)and The 32-item Hypomania Symptom Check List(HCL-32)were used to explore the history of Manic/hypomanic episode.17-Hamilton Depression Scale,Hamilton Anxiety Scale and Young Mania Rating Scale were used to assess the severity of clinical symptoms.Enzyme-linked immunosorbent assay(ELISA)was used to detect the concentration of serum Gln,Glu,GABA and GAD.RT-PCR was used to quantitatively detect the levels of GABA_Areceptor alpha 1subunit mRNA,alpha 2 subunit mRNA and NMDA receptor NR1 subunit mRNA.SPSS 19.0 was used for statistical analysis of all data.Results:1.Compared with BDD,the age of onset in MDD group was later.The total scores of HAMA,psychoanxiety factor,somatic anxiety factor,core symptoms of depression,HAMD,body weight factor and sleep disorder factor in MDD group were higher than those in BDD group(P<0.05).2.The total PSQI scores and factor scores in insomnia disorder group were higher than those of MDD group and BDD group(F=24.14,P<0.01).The total score of PSQI,sleep latency factor,sleep persistence factor and sleep efficiency factor in MDD group were higher than those in BDD group,and the difference was statistically significant(P<0.05).3.There was no significant difference in serum Gln levels among MDD group,BDD group,insomnia disorder group and healthy control group(F=0.67,P=0.570);serum Glu levels in MDD group,BDD group and insomnia disorder group were higher than those in control group(F=10.97,P<0.001),while serum GABA levels(F=5.61,P=0.001),GAD levels(F=8.74,P<0.001)were lower than those in control group,However,there was no significant difference in serum Glu,GABA and GAD levels among the three case groups(P>0.05).4.The ratio of Glu/GABA in insomnia disorder group was higher than that in MDD group,BDD group and healthy control group(F=3.13,P=0.035).The ratio of Glu/GABA in MDD group and BDD group was also higher than that in control group,but there was no significant difference between MDD group and BDD group(P>0.05).5.Serum GABA level was negatively correlated with HAMA total score(r=-0.34,P=0.021),HAMD total score(r=-0.46,P=0.001)and depression core symptom score(r=-0.32,P=0.031)in MDD group..6.Serum Gln level was positively correlated with total HAMD score in BDD group(r=0.52,P=0.037),but not with other factors(P>0.05).7.There was a negative correlation between GABA level and PSQI total score in insomnia disorder group(r=-0.38,P=0.040).8.Compared with the control group,the levels of serum GABA_Areceptor alpha1 subunit mRNA,alpha 2 subunit mRNA in MDD,BDD and insomnia disorder groups decreased,but the levels of NR1 mRNA increased.However,there was no significant difference in the levels of alpha-1 mRNA,alpha-2 mRNA and NR1 mRNA between the three case groups(P>0.05).9.In MDD group,the level of alpha 1 mRNA was positively correlated with serum Glu level(r=0.30,P=0.042),and the level of alpha 2 mRNA was positively correlated with age(r=0.48,P=0.01),while the level of NR1 mRNA was negatively correlated with age(r=-0.58,P=0.01),total course of disease(r=-0.42,P=0.02)and serum GAD level(r=-0.34,P=0.02).10.In insomnia group,the level of alpha 2 gene was positively correlated with age(r=0.48,P=0.007),while the level of NR1 gene was negatively correlated with age(r=-0.58,P=0.001),total course of disease(r=-0.42,P=0.022).Conclusion:1.Abnormal levels of key substances Glu,GABA and GAD in Glu/GABA-Gln metabolic pathway and abnormal expressions of GABA_Areceptor subunits alpha 1 mRNA,alpha 2 mRNA and NMDA receptor NR1 mRNA are related to the pathological mechanism of insomnia disorder,MDD and BDD.2.Glu/GABA-Gln metabolic abnormality is the common pathological mechanism of MDD,BDD and insomnia disorder.Insomnia disorder is more serious in the imbalance of Glueric excitatory neurons/GABAeric inhibitory neurons.3.The abnormalities of MDD and BDD in Glu/GABA-Gln metabolic pathway are similar,so they can not be used as biological markers for differential diagnosis of MDD and BDD.