Study on the Gut Microbial Mechanism of Negative Symptoms of Schizophrenia

Overview

Negative symptoms are one of the five-dimensional symptoms of patients with schizophrenia, and medications are not effective in treating negative symptoms. The mechanism of negative symptoms of schizophrenia is unknown, which may be related to insufficient dopamine function of the prefrontal cortex. Amisulpride is a D2/D3 receptor antagonist, which can improve negative symptoms. Intestinal microbes are related to central nervous system mental diseases. Animal studies have found that changes in the intestinal microflora are related to schizophrenia. Clinical studies have found that the gut microbes of patients with schizophrenia are different from those of normal healthy people. Therefore, we are trying to discover the changes of gut microbes in patients with effective amisulpride treatment, and to improve the negative symptoms of schizophrenia patients through the intestinal immune system. The mechanism of brain relationship provides direction, and also provides a new way for the drug treatment of negative symptoms.

Negative symptoms are one of the five-dimensional symptoms of patients with schizophrenia. Drug treatment of negative symptoms is not effective. Even if the positive symptoms are relieved, the negative symptoms continue to exist, which seriously affects the personal family social function and is an important risk factor for poor prognosis. The mechanism of negative symptoms of schizophrenia is unknown, which may be related to insufficient dopamine function of the prefrontal cortex, but the pathogenesis is still not fully explained. Amisulpride is a D2/D3 receptor antagonist, which can improve negative symptoms, but the mechanism is not clear. Intestinal microbes are related to central nervous system psychiatric diseases, and intestinal flora imbalance may be an important cause of autism, anxiety, depression, schizophrenia and other mental and psychological diseases. Under pathological conditions, when the intestinal microbiome is disturbed or the intestinal mucosal barrier is destroyed, microbial-related molecules stimulate macrophages and dendritic cells to produce pro-inflammatory cytokines, which in turn activate adaptive immune cells, leading to the destruction of immune homeostasis and enteric nerves The system can also interact with the central nervous system through the brain-gut axis. Intestinal microbes may also influence the occurrence of mental illness through metabolites. Animal studies have found that changes in the intestinal microflora are related to schizophrenia. Clinical studies have found that the gut microbes of patients with schizophrenia are different from those of normal healthy people. Therefore, we are trying to discover the changes of gut microbes in patients with effective amisulpride treatment, and to improve the negative symptoms of schizophrenia patients through the intestinal immune system. The mechanism of brain relationship provides direction, and also provides a new way for the drug treatment of negative symptoms. This study intends to select 30 patients with schizophrenia with dominant negative symptoms (study group) and 15 healthy people with similar living environment (control group), and the study group will be treated with amisulpride (flexible treatment), negative symptom factor The score reduction rate reached 20% for the effective group. Followed up for 8 weeks, fresh stool samples were collected at the baseline, 2, 4, and 8 weekends for 16S rRNA sequencing and short-chain fatty acid detection, and whole blood samples for immune factors (IL-1β, IL-6, IL-10, TNF) -α) Test to assess the negative symptom factor scores of PANSS, CDSS, CGI, TESS, SAS, and Barnes akathisia, and evaluate the patient's negative symptoms, depressive symptoms, efficacy and adverse reactions in turn. Comparing the differences in the intestinal microflora of the two groups at baseline, the correlation between the changes of the intestinal microflora of the effective group of amisulpride and the immune factors and negative symptoms. To understand the pathogenesis of schizophrenia patients with dominant negative symptoms through the gut microbiota-brain axis.