The microbiota–gut–brain axis plays a critical role in the pathogenesis of major depressive disorder (MDD) and related subclinical symptoms. However, studies on the gut microbiota in MDD are inconsistent, and data on MDD's effects on sleep are lacking. This study aimed to analyze the gut microbiota composition and sleep quality of patients with MDD. We performed 16S rRNA sequencing of stool samples from 36 patients with MDD and 45 healthy controls (HC). Sleep quality was assessed using the Pittsburgh Sleep Quality Index, depressive severity with the Hamilton Depression Scale, and insomnia severity using the Insomnia Severity Index. Forty-eight microbiota targets showed significant differences between MDD and HC. In MDD, six microbiota targets were associated with the severity of depression, 11 with sleep quality, and 3 with sleep severity. At the genus level, Dorea was simultaneously related to depression and sleep quality, while Intestinibacter was more closely related to sleep problems. Coprococcus and Intestinibacter were associated with sleep quality independent of the severity of depression. In conclusion, the present findings enable a better understanding of the relationship between gut microbiota and MDD-related symptoms. Gut microbiota alterations may become potential biomarkers and/or treatment targets for sleep quality in MDD.

Background: There is currently no effective treatment for cognitive impairment associated with schizophrenia (CIAS). Recent studies have shown that increased histamine levels in the brain may help to improve CIAS symptoms. Betahistine is an H1-receptor agonist and H3-receptor antagonist. This study evaluated the effect of high-dose betahistine on cognitive function as well as its safety in Chinese Han patients with schizophrenia.Methods: This randomized double-blind, placebo-controlled trial enrolled 89 patients with schizophrenia who were randomly administered betahistine (72 mg/d) or placebo for 12 weeks. At baseline and at 4, 8, and 12 weeks after commencing the intervention, we measured changes in cognitive function and clinical symptoms using the MATRICS Consensus Cognitive Battery (MCCB) and Positive and Negative Syndrome Scale (PANSS), respectively. Furthermore, we used the Treatment Emergent Symptom Scale (TESS) to assess the adverse effects of the patients' medications.Results: Compared to the placebo group, the betahistine group showed significant improvements in the MCCB composite score after 12 weeks of treatment (p = 0.003) as well as improvements in MCCB verbal learning (p = 0.02) and visual learning (p = 0.001) domain scores. However, there were no significant improvements in the PANSS total scores or subscores (p > 0.05). Generally, high-dose betahistine treatment was considered safe in patients with schizophrenia.Conclusions: Additional use of high-dose betahistine can effectively improve cognitive function but not psychiatric symptoms in patients with schizophrenia. Betahistine (72 mg/d) is well tolerated by Chinese Han patients with schizophrenia.Trial Registration:chictr.org.cn, identifier: ChiCTR1900021078. http://www.chictr.org.cn/edit.aspx?pid=35484&htm=4

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