No abstract

The mechanism of bipolar disorder is unclear. Growing evidence indicates that gut microbiota plays a pivotal role in mental disorders. This study aimed to find out changes in the gut microbiota in bipolar depression (BD) subjects following treatment with quetiapine and evaluate their correlations with the brain and immune function. Totally 36 subjects with BD and 27 healthy controls (HCs) were recruited. The severity of depression was evaluated with the Montgomery-Asberg depression rating scale (MADRS). At baseline, fecal samples were collected and analyzed by quantitative polymerase chain reaction (qPCR). T lymphocyte subsets were measured to examine immune function. Near-infrared spectroscopy (NIRS) was used to assess brain function. All BD subjects received quetiapine treatment (300 mg/d) for four weeks, following which the fecal microbiota and immune profiles were reexamined. Here, we first put forward the new concept of brain-gut coefficient of balance (B-GCB), which referred to the ratio of [oxygenated hemoglobin]/(Bifidobacteria to Enterobacteriaceae ratio), to analyze the linkage between the gut microbiota and brain function. At baseline, the CD3+ T cell proportion was positively correlated with log10 Enterobacter spp count, whereas the correlativity between the other bacteria and immune profiles were negative. Log10 B-GCB was positively correlated with CD3+ T cell proportion. In subjects with BD, counts of Faecalibacterium prausnitzii, Bacteroides–Prevotella group, Atopobium Cluster, Enterobacter spp, and Clostridium Cluster IV were higher, whereas the log10 (B/E) were lower than HCs (B/E refers to Bifidobacteria to Enterobacteriaceae ratio and represents microbial colonization resistance). After treatment, MADRS scores were reduced, whereas the levels of Eubacterium rectale, Bifidobacteria, and B/E increased. The composition of the gut microbiota and its relationship to brain function were altered in BD subjects. Quetiapine treatment was effective for depression and influenced the composition of gut microbiota in patients. Clinical Trial Registration: , identifier ChiCTR-COC-17011401, URL: .

The clinical and cognitive responses to repetitive transcranial magnetic stimulation (rTMS) in bipolar II depressed patients remain unclear. In this study, thirty-eight bipolar II depressed patients were randomly assigned into three groups: (i) left high-frequency (n = 12), (ii) right low-frequency (n = 13), (iii) sham stimulation (n = 13), and underwent four-week rTMS with quetiapine concomitantly. Clinical efficacy was evaluated at baseline and weekly intervals using the 17-item Hamilton Depression Rating Scale (HDRS-17) and Montgomery-Asberg Depression Rating Scale (MADRS). Cognitive functioning was assessed before and after the study with the Wisconsin Card Sorting Test (WCST), Stroop Word-Color Interference Test (Stroop), and Trail Making Test (TMT). Thirty-five patients were included in the final analysis. Overall, the mean scores of both the HDRS-17 and the MADRS significantly decreased over the 4-week trial, which did not differ among the three groups. Exploratory analyses revealed no differences in factor scores of HDRS-17s, or in response or remission rates. Scores of WCST, Stroop, or TMT did not differ across the three groups. These findings indicated active rTMS combined with quetiapine was not superior to quetiapine monotherapy in improving depressive symptoms or cognitive performance in patients with bipolar II depression.