| Objective:Depression is a chronic mental disorder characterized by low mood,lack of interest,slow thinking,worthless feeling and guilt,in addition to mental symptoms,depression is often accompanied by gastrointestinal symptoms including loss of appetite,abdominal pain,constipation and gastrointestinal symptoms is closely related to the severity of depression.Depression with gastrointestinal symptoms may be a subtype of depression.However,the biological characteristics and clinical outcomes of depressed patients with gastrointestinal symptoms have not been studied.This study choose the first-episode untreated depression patients with depressio,the 16 Sr RNA sequencing technology was used to test the intestinal flora,using Enzyme-linked immunosorbent assay(ELISA)to detect plasma inflammatory factors,using magnetic resonance to examinate brain structure and function changes of subjects.The characteristics of gut microbes,immune and brain imaging of depression with gastrointestinal symptoms were analyzed.Methods:1.Characteristics and correlation analysis of gastrointestinal symptoms in patients with depression.123 patients with first-episode untreated depression were collected,and general data of subjects were collected after signing informed consent.HAMD,HAMA,GSRS,QOL and SF-12 were used to evaluate depression symptoms,anxiety symptoms,gastrointestinal symptoms,quality of life,physical health and mental health.According to the gastrointestinal symptoms,patients with depression were divided into tho groups,patient with gastrointestinal symptoms(n=83)and without gastrointestinal symptoms(n=40).The characteristics of gastrointestinal symptoms of patients with depression were analyzed,and clinical data of subjects in the two groups were compared.2.Changes in peripheral inflammatory cytokines in depressive patients with gastrointestinal symptoms.54 patients with first-episode untreated depression with blood samples were collected,including 35 patients with gastrointestinal symptoms and 19 patients without gastrointestinal symptoms,and 33 healthy subjects matched in age,sex,education years and body mass index were collected.Plasma inflammatory factors: interleukin-1(IL-1),interleukin-6(IL-6),interleukin-10(IL-10),tumor necrosis factor-?(TNF-?)and Creactive protein(CRP)were detected by ELISA.The levels of inflammatory factors in the three groups were compared and the correlation was analyzed.3.Analysis on the characteristics of intestinal flora in patients with depression accompanied by gastrointestinal symptoms.41 patients with depression with stool samples were selected,including 25 patients with gastrointestinal symptoms and 16 patients without gastrointestinal symptoms.44 healthy subjects matched in age,sex,years of education,body mass index,etc were selected.The16 Sr RNA sequencing technology was used to test the intestinal flora.Then the intestinal flora diversity and abundance of the three groups were compared to find the gut microbiota related to depression symptoms and gastrointestinal symptoms,and the correlation analysis was conducted.Then the therapeutic effect was observed with selective serotonin reuptake inhibitors(SSRIs)and probiotics.4.Changes in brain structure and function in depressive patients accompanied by gastrointestinal symptoms.Selected 58 depressive patients with MRI data,including 36 patients with gastrointestinal symptoms and 22 patients without gastrointestinal symptoms and 30 healthy subjects matched in age,sex,education years and body mass index were collected.The Regional Homogeneity(Re Ho)and Gray Matter Volume(GMV)were obtained after preprocessing of MRI data.The clinical data and brain imaging data of 3 groups of subjects were compared and correlation analysis was conducted.Results:1.67.48%(83/123)of the depressed patients were accompanied by gastrointestinal symptoms,and the incidence of appetite loss,nausea,vomiting,bowel discomfort,abdominal distension and early satiety were 79.52%(66/83),69.88%(58/83),67.47%(56/83),61.45%(51/83),61.45%(51/83),The total scores of HAMD(21.00 ±4.00VS18.90 ± 4.40,P <0.01)and HAMA(21.10 ± 5.58VS18.07 ± 4.31,P = 0.039)increased significantly in depressed patients with gastrointestinal symptoms.QOL(14.672.05VS16.42 2.77,P <0.01)and PCS(43.36 8.40 VS 50.40 9.57,P =0.023)score significantly decreased,while MCS(23.95 6.85 VS 21.85 7.26,P =0.38)showed no significant difference between two groups?2.Compared with the healthy group,CRP in peripheral blood of patients with depression was significantly increased(t=2.06,P = 0.043),and there was no significant difference in IL-1,IL-6,IL-10 and TNF-?(P >0.05).Compared with the healthy group,there was no significant difference in CRP in the group without gastrointestinal symptoms(P >0.05).However,CRP in the depression with gastrointestinal symptoms was significantly increased(t=2.05,P = 0.046).There was no significant difference in CRP,IL-1,IL-6,IL-10 and TNF-? between groups with and without gastrointestinal symptoms(P >0.05);The correlation between CRP,IL-1,IL-6,IL-10,TNF-? and 16 gastrointestinal symptoms in GIRS was analyzed.It was found that CRP was positively correlated with abdominal distension(r=0.27,P=0.045),fecal dry(r=0.28,P=0.044)and defecation sense(r=0.34,P=0.012).IL-1 was positively correlated with nausea(r=0.30,P=0.027).Il-6 was positively correlated with defecation urgency(r=0.30,P=0.026).3.A total of 5661,964 high quality 16 Sr RNA sequences were obtained,which were divided into 35,488 operational taxa(OTUs)at 97% similarity level.According to the ?-diversity analysis,Simpson index of depressed patients was significantly lower than that of healthy subjects(P =0.022).According to the ?-diversity analysis,we found that the intestinal microbial community between the depressed patients and the healthy control group showed significant differences,and the difference between the two groups was significantly greater than that within the group(P =0.001).Using the random forest method,we obtained a total of 50 different otus(model accuracy rate was 92.9%)that could identify the two groups of subjects.These intestinal flora were mainly attributed to 20 genera,of which 8 genera were highly expressed in patients with depression and 12 genera were highly expressed in healthy people.Clostridia and Clostridium in the intestines of depressed patients with gastrointestinal symptoms were significantly lower than those without gastrointestinal symptoms,and Clostridium was negatively correlated with blood CRP(R=-0.302,P=0.015)and gastrointestinal symptoms(R=-0.399,P=0.011).After SSRI antidepressant treatment for8 W,there was no significant difference in response rate and HAMD score reduction rate between the two groups(P>0.05).Gastrointestinal symptoms of depression patients with gastrointestinal symptoms significantly improved(t=7.76,P = 0.001).The HAMD score reduction rate in patients with depression with gastrointestinal symptoms was(0.68±0.17 VS 0.57±0.23,P <0.037)and the response rate(75.0% VS 53.3%,P=0.163)was higher than that of the group without gastrointestinal symptoms.4.Significant differences in both GMV and Re Ho were observed among the three groups for the right parahippocampal gyrus,left precentral gyrus,left middle frontal gyrus,right superior frontal gyrus,right middle frontal gyrus,and left inferior orbitofrontal gyrus(Alpha Sim correction,P <0.001).The GI symptoms group exhibited significantly decreased GMV and Re Ho in the left middle frontal gyrus,precentral gyrus,the right superior frontal gyrus,and middle frontal gyrus,as well as increased Re Ho in the left superior temporal gyrus at a higher level than the non-GI symptoms group.(Alpha Sim correction,P <0.001).These altered brain areas were correlated with GI symptoms(P<0.001),but not depressive symptoms(P>0.05).Conclusion:1.Depressed patients with gastrointestinal symptoms have more severe symptoms of depression and anxiety,worse quality of life and physical health.2.CRP in peripheral blood of patients with gastrointestinal symptoms increased,and CRP,IL-1,and IL-6 levels were associated with gastrointestinal symptoms.3.Decreased intestinal Clostridium in depressed patients with gastrointestinal symptoms is associated with peripheral blood CRP and gastrointestinal symptoms.4.GMV and Re Ho were significantly decreased in the left middle frontal gyrus,left anterior central gyrus,right superior frontal gyrus and right middle frontal gyrus in patients with gastrointestinal symptoms and these brain regions are associated with gastrointestinal symptoms. |
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