| ?Objective?Based on the clinical phenomenon that the traditional antidepressant drug is not so well and the inflammatory diseases are likely to occur with depression,the research is trying to evaluate the patients' mood and cognitive characteristics and detecting inflammation and brain white matter damage index,and serum and urine metabolites were analyzed,thus exploring the possible mechanism of inflammation in depression,providing a new target for the study of antidepressant treatment for inflammatory damage,so as to improve the anti-depression therapy clinical efficiency and cure rate.?Methods?We have randomized prospectively adopted 59 asthma outpatients in our hospital for one year,including 33 outpatients of asthma without depression(asthma control group,A group),26 outpatients of asthma patients with depression(asthma with depression group,A+D group).At the same time,we also adopted 25 patients with depression in the Department of Neurology of the psychological clinic(depression group,D group),and 28 normal patients(healthy control group,N group).The demographic data registration,emotional and cognitive scale assessment,inflammatory and white matter damage related indicators as well as serum and urine metabonomics were carried out in four groups of patients.?Results?1.clinical features: Anxiety comorbidity: Among the four groups,the incidence of anxiety of A group patients is lowest,and belong to mild anxiety anxiety;A+D group had the highest incidence in the four groups,which accounted for 11.54% of severe anxiety;The degree of anxiety in the D group were mainly mild and moderate.Comorbidity of cognitive impairment: A,D,A+D three groups all had cognitive impairment,A+D group had the highest incidence(73.1%),followed by D group(52%)and A group(45.45%),compared with N group,there was a significant difference(P<0.01).Cognitive domain impairment: Compared with D group,the scores of attention,language and orientation in A+D group were significantly decreased.2.Inflammation and cerebral white matter damage index: Compared with the N group,the serum levels of interleukin-1beta(IL-1 beta),interleukin-6(IL-6)and tumor necrosis factor-a(TNF-a)in the serum of D,A and A+D groups were increased.Compared with the N group,the high mobility group protein 1(HMGB1)and the axon guidance factor(Netrin-1)in the D group and the A+D group were all significantly increased(P<0.05).Compared with the N group,the serum myelin basic protein(MBP)and oligodendrocyte glycoprotein(MOG)in the D group had a rising trend.Compared with group A,the serum MOG and MBP in group A+D were significantly increased(P<0.05).Compared with group D,the MOG and MBP in serum of A+D group showed an upward trend,among which MBP increased significantly(P<0.05).Compared with group N,the serum levels of glial cell line derived neurotrophic factor(GDNF)in group D,A and A+D were decreased.3.Metabonomics:Metabolic differences of four groups in serum including urea,acetyl-carnitine,deoxythymidylic acid,hypoxanthine and so on.The metabolite related metabolic pathways in serum include purine metabolism,pyrimidine metabolism,sheath lipid metabolism,glycerol phospholipid metabolism,amino acid metabolism,peanut four acid metabolism and citric acid metabolism.The different metabolites of urine in the four groups were proline,glyceric acid,oleic acid and so on.Metabolic pathways related to metabolites include amino acid metabolism,pantothenate and coenzyme-A metabolism,purine metabolism,pyrimidine metabolism,glycerol phospholipid metabolism,sheath metabolism and citric acid metabolism.Further comparison between groups showed that compared with group A,in group A+D,acetyl-carnitine,citric acid and glycerol phospholipids were increased,1-sphingosine were decreased and urinary glutamic acid were increased with statistical difference(P<0.05).Compared with group D,in A+D group,phenylalanine in serum were decreased,acetyl-carnitine and phospholipid were increased,phenylalanine in urine were decreased,tyrosine were decreased,and there was a significant difference(P<0.05).Compared with group N,the serum glycerol phospholipids in group D were increased,tryptophan in urine were decreased,phenylalanine were decreased,tyrosine were decreased,and the difference was statistically significant(P<0.05).?Conclusions?1.Depression,anxiety,and cognitive disorders all had comorbidities.Asthmatic depressive patients had the highest incidence of anxiety and the highest degree of comorbidity.The highest incidence of cognitive impairment was associated with decreased attention,language,and orientation.This shows that asthma and depression are more prone to comorbid conditions of affective and cognitive disorders.2.There was no significant difference in the acute inflammation index between the groups(IL-1??IL-6?TNF-a),but the advanced inflammatory factor HMGB1 and the anti-inflammatory index Netrin-1 were significantly higher in depressed patients or asthmatic patients with depression,suggesting that depression is a chronic persistent inflammatory reaction.These two indicators may be potential inflammatory biomarkers for the diagnosis of depression.3.Indicators of white matter damage in each group of patients: MBP and MOG were the related indexes of brain white matter injury.Compared with the normal person,the white matter damage index of the depression patients was increased,indicating that the depressive patients had white matter damage.Compared with normal person or asthma patients,the index of white matter injury in asthma and depression patients increased significantly,indicating that the white matter damage was more serious in patients with depression.Compared with depression patients,the serum levels of MOG and MBP in asthma patients were increased,and the MBP increased significantly,indicating that the white matter of inflammatory depression was more serious.GDNF is a glial cell derived neurotrophic factor,which was decreased in the peripheral blood of asthmatic patients with depression,which indirectly reflects the manifestations of brain white matter injury.4.Metabolomics studies have shown that both asthma and depression itself have metabolic changes,and the metabolites of blood urine in asthmatic and depressive patients reflect impaired glucose metabolism and increased glycogenoglucosamine mobilization,which reflects myelination Phospholipid metabolism,as well as abnormal glutamate metabolism in neurotransmitter precursors.From the perspective of metabolism,the phenomenon of inflammatory demyelinating myelin damage was further verified,and related metabolites and possible pathways were found,providing a basis for further elucidating the mechanism of inflammation-induced depression. |
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