首发抑郁症患者肠道菌群与认知情绪调节关系研究

背景　近年来抑郁症和肠道菌群的相关研究大多集中于动物实验，而人体肠道菌群的相关研究相对较少，结合心理特征的研究则更少。目的　了解首发抑郁症患者与健康人群在肠道菌群、认知情绪调节方面的差异，进一步探讨抑郁症、肠道菌群及认知情绪调节之间的关系。方法　选取2017年1-12月就诊于宁夏医科大学总医院心理卫生中心门诊的首发抑郁症患者30例（抑郁症组），同期选取宁夏“十三五”科技重大项目流调体检健康志愿者31例（对照组）。完成一般情况调查问卷、汉密尔顿抑郁量表、认知情绪调节量表（CERQ）的评定与粪便的收集；采用高通量测序及生物信息学方法分析微生物群落多样性和丰度变化；探讨情绪调节策略、抑郁严重程度与肠道菌群的相关性。结果　抑郁症组和对照组一般情况（年龄、性别、BMI、吸烟、文化程度）比较，差异无统计学意义（P>0.05）。本研究以97%的相似性将所有样本的有效序列聚类为Operational Taxonomic Units（OTUs），所得稀释曲线趋向平坦，说明测序数据量合理。抑郁症组与对照组肠道菌群多样性指数比较，差异无统计学意义（P>0.05）。与对照组相比，在门水平，抑郁症组厚壁菌门、放线菌门、柔壁菌门丰度降低，拟杆菌门丰度增高（P<0.05）；在属水平，抑郁症组Ruminococcus、Subdoligranulum、Enterobacter、Coprococcus、Bifidobacterium、Lactobacillus菌属减少，而Klebsiella、Flavonifractor、Bacteroides菌属增多（P<0.05）。LEfSe分析显示，抑郁症组肠道菌群中主要以拟杆菌、产碱菌科（Alcaligenaceae），伯克菌目（Burkholderiales），Β-变形菌纲、Erysipelotrichaceae、幽门螺杆菌等致病菌为主；对照组以厚壁菌门、双歧杆菌、Subdoligranulum、乳酸杆菌等有益菌为优势菌。抑郁症组自我责难、沉思、灾难化、责难他人分量表得分高于对照组，积极重新评价、理性分析分量表得分低于对照组（P<0.05）。CERQ分量表中自我责难得分与Enterobacter菌属呈正相关，与Odoribacter、Alistipes菌属呈负相关（P<0.05）；沉思分量表得分与Subdoligranulum、Alistipes、Faecalibacterium、Odoribacter菌属呈负相关（P<0.05）；重新关注计划、积极重新评价分量表得分与Weissella菌属呈正相关（P<0.05）；灾难化分量表得分与Dialister菌属呈负相关（P<0.05）。抑郁严重程度与拟杆菌门及Flavonifractor菌属呈正相关（P<0.05），与Ruminococcus、Subdoligranulum、Coprococcus、Dialister、Odoribacter、Faecalibacterium、Butyricimonas菌属呈负相关（P<0.05）。结论　抑郁症患者与健康对照者在肠道菌群、认知情绪调节策略方面均有较大差异，情绪调节策略自我责难、沉思、灾难化，肠道菌群条件致病菌的增多及丁酸盐产生菌、益生菌的减少与抑郁症密切相关。

Relationship between Intestinal Flora and Cognitive Emotion Regulation in Patients with First-episode Depression

Background　Recent studies about the relationship of intestinal flora with depression are mostly in animal models，but rarely in humans，and those about intestinal flora and psychological characteristics in humans are even more rare.Objective　To explore the differences in intestinal flora and cognitive emotion regulation between first-episode depression patients and healthy people，and to further explore the relationship of depression with intestinal flora and cognitive emotion regulation strategies.Methods　Participants were enrolled during January to December 2017，including 30 outpatients with first-onset depression（depression group） from Mental Health Center Clinic，Ningxia Medical University General Hospital，and 31 healthy physical examinees（control group） who participated in an epidemiological survey of a major scientific and technological project of Ningxia's 13th Five-Year Plan.Both groups were surveyed with the General Questionnaire，Hamilton Depression Rating Scale（HAMD），and Cognitive Emotion Regulation Questionnaire（CERQ）.High-throughput sequencing and bioinformatics techniques were used to measure the diversity and abundance of microflora in fecal samples of the participants.The relationship of depression with intestinal flora and cognitive emotion regulation was analyzed.Results　Both groups had no significant differences in general conditions（gender ratio，mean age，and BMI，smoking prevalence，education level distribution）（P>0.05）.In this study，the effective sequences of all samples were clustered into Operational Taxonomic Units（OTUs） at a 97% similarity level，and the resulting rarefaction curves tended to be flat，indicating that the amount of sequencing data was reasonable.There was no significant difference in the diversity index of intestinal microflora between these two groups（P>0.05）.Compared to the control group，depression group showed significantly decreased abundance of the Firmicutes，Actinobacteria，and Tenericutes，and significantly increased abundance of the Bacteroidetes（P<0.05） at the level of phylum.At the level of genus，depression group showed lower ratios of Ruminococcus，Subdoligranulum，Enterobacter，Coprococcus，Bifidobacterium，Lactobacillus，and higher ratios of the Klebsiella，Flavonifractor and Bacteroides（P<0.05）.LEfSe analysis showed that the intestinal flora of the depression group mainly consisted of pathogenic bacteria such as Bacteroides，Alcaligenaceae，Burkholderiales，Betaproteobacteria，Erysipelotrichaceae，Helicobacter pylori.In the control group，beneficial bacteria such as Firmicutes，Bifidobacteriales，Subdoligranulum，and Lactobacillales were dominant bacteria.Depression group had higher mean scores of self-blame，rumination，and catastrophizing subscales，and lower mean scores of positive reappraisal，and putting into perspective subscales（P<0.05）.Self-blame subscale score was positively correlated with Enterobacter，and was negatively correlated with Odoribacter and Alistipes（P<0.05）.Rumination subscale score was negatively correlated with Subdoligranulum，Alistipes，Faecalibacterium，and Odoribacter（P<0.05）.Positive refocusing，planning and positive reappaisal subscales scores were positively correlated with Weissella（P<0.05）.Catastrophizing subscale score was negatively correlated with Dialister（P<0.05）.The severity of depression was positively correlated with the relative abundance of Bacteroides and Flavonifractor（P<0.05），and was negatively correlated with Ruminococcus，Subdoligranulum，Coprococcus，Dialister，Odoribacter，Faecalibacterium and Butyricimonas（P<0.05）.Conclusion　There are significant differences in intestinal flora and cognitive emotion regulation strategies between patients with depression and healthy controls.Three emotional regulation strategies（self-blame，rumination，and catastrophizing），increased intestinal pathogens and the reduction of probiotics bacteria and butyrate-producing bacteria are related to depression closely.