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Introduction: Repetitive transcranial magnetic stimulation (rTMS) is a clinically useful therapy for depression. However, the effects of rTMS on the metabolism of fatty acids (FAs) and the composition of gut microbiota in depression are not well established. Methods: Mice received rTMS (15 Hz, 1.26 T) for seven consecutive days after exposure to chronic unpredictable mild stress (CUMS). The subsequent depressive‐like behaviors, the composition of gut microbiota of stool samples, as well as medium‐ and long‐chain fatty acids (MLCFAs) in the plasma, prefrontal cortex (PFC), and hippocampus (HPC) were evaluated. Results: CUMS induced remarkable changes in gut microbiotas and fatty acids, specifically in community diversity of gut microbiotas and PUFAs in the brain. 15 Hz rTMS treatment alleviates depressive‐like behaviors and partially normalized CUMS induced alterations of microbiotas and MLCFAs, especially the abundance of Cyanobacteria, Actinobacteriota, and levels of polyunsaturated fatty acids (PUFAs) in the hippocampus and PFC. Conclusion: These findings revealed that the modulation of gut microbiotas and PUFAs metabolism might partly contribute to the antidepressant effect of rTMS. [ABSTRACT FROM AUTHOR]

Intestinal dysbacteriosis has frequently been involved in the context of depression. Nonetheless, only scant information is available about the features and functional changes of gut microbiota in female middle-aged depression (MAD). This study aims to explore whether there are characteristic changes in the gut microbes of female MAD and whether these changes are associated with depressive-like behaviors. Meanwhile, this study observed alterations in the lipid metabolism function of gut microbes and further examined changes in plasma medium- and long-chain fatty acids (MLCFAs) in mice that underwent fecal microbiota transplantation (FMT). Stool samples obtained from 31 MAD, along with 24 healthy individuals (HC) were analyzed by 16 S rRNA gene sequencing. Meanwhile, 14-month-old female C57BL/6J mice received antibiotic cocktails and then oral gavage of the microbiota suspension of MAD or HC for 3 weeks to reconstruct gut microbiota. The subsequent depressive-like behaviors, the composition of gut microbiota, as well as MLCFAs in the plasma were evaluated. A noteworthy disruption in gut microbial composition in MAD individuals compared to HC was observed. Several distinct bacterial taxa, including Dorea , Butyricicoccus , and Blautia , demonstrated associations with the demographic variables. A particular microbial panel encompassing 49 genera effectively differentiated MAD patients from HC (AUC = 0.82). Fecal microbiome transplantation from MAD subjects led to depressive-like behaviors and dysfunction of plasma MLCFAs in mice. These findings suggest that microbial dysbiosis is linked to the pathogenesis of MAD, and its role may be associated with the regulation of MLCFAs metabolism. [Display omitted] • Gut microbiome was altered in MAD. • A panel (49 genera) that can discriminate MAD from HC was identified (AUC = 0.82). • FMT induces depressive-like behaviors in recipient mice. • FMT disturbs plasma long- and medium-chain fatty acids. [ABSTRACT FROM AUTHOR]

Background: The association between abnormal gut microbiome composition and depression is well established. However, the composition and functional capacity of the gut microbiota regarding depressed women has been poorly addressed.Methods: Stool samples from 62 female patients with major depressive disorder (MDD) and 46 healthy controls (Con) were analyzed by 16S rRNA gene sequencing; Twenty fecal samples from the patient group and 21 fecal samples from the Con group were further analyzed by shotgun metagenomic sequencing. Psychiatric symptoms and psychological, social, and professional functioning was also assessed.Results: Phylum Bacteroidetes, proteobaeteria, and Fusobacteria were greatly enriched in patients with MDD, while the Firmicutes and Actinobacteria phyla were consistently higher in Con. Notably, 18 microbial markers were identified on a random forest model and achieve an area under the curve of 0.92 between patients with MDD and the Con group. Forty-five species and their associated function were identified with statistically significant differences between patients with MDD and the Con group.Limitations: The number of recruited samples, especially samples enrolled for shotgun metagenomic sequencing was relatively small, and the stool samples were collected only at baseline, making it difficult to establish a causal association between changes in gut microbiota compositions and disease remission.Conclusions: This study characterizes the gut microbiota and their related function in female MDD. The gut microbiota-based biomarkers may be helpful in diagnosis and the altered gut microbial metabolites may contribute to the pathogenesis of MDD in women, representing potential microbial targets. [ABSTRACT FROM AUTHOR]

Depression accounts for a high proportion of neuropsychiatric disorders and is associated with abnormal states of neurons in specific brain regions. Microglia play a pivotal role in the inflammatory state during depression development; however, the exact mechanism underlying chronic mood states remains unknown. Thus, the present study aimed to determine whether microRNAs (miRNAs) alleviate stress-induced depression-like behavior in mice by regulating the expression levels of their target genes, explore the role of neuroinflammation induced by microglial activation in the pathogenesis and progression of depression, and determine whether the role of the miR-29a-5p/transmembrane protein 33 (TMEM33) axis. In this study, chronic unpredictable mild stress (CUMS) mouse depression model, various behavioral tests, western blotting, dual-luciferase reporter assay, enzyme-linked immunosorbent assay, real-time quantitative reverse transcription PCR, immunofluorescence and lentivirus-mediated gene transfer were used. After exposure to the CUMS paradigm, miR-29a-5p was significantly down-regulated. This downregulation subsequently promoted the polarization of microglia M1 by upregulating the expression of TMEM33, resulting in enhanced inflammatory chemokines affecting neurons. Conversely, the upregulation of miR-29a-5p within the prefrontal cortex (PFC) suppressed TMEM33 expression, facilitated microglia M2-polarization, and ameliorated depressive-like behavior. Only rodent models of depression were used, and human samples were not included. The results of this study suggest that miR-29a-5p deficits within the PFC mediate microglial anomalies and contribute to depressive-like behaviors. miR-29a-5p and TMEM33 may, therefore, serve as potential therapeutic targets for the treatment of depression. • miR-29a-5p is downregulated by chronic stress. • Upregulation of miR-29a-5p improved depression-like behavior. • miR-29a-5p deficits in prefrontal cortex mediate microglial anomalies. • miR-29a-5p and TMEM33 are potential therapeutic targets for depression treatment. [ABSTRACT FROM AUTHOR]

• A cross-sectional study was conducted on 1289 young Chinese outpatients with first-episode medication-naïve major depressive disorder. • The prevalence of abnormal glucose metabolism was 12.57%. • Higher TSH levels and more severe anxiety symptoms were associated with fasting glucose levels in young patients with first-episode medication-naïve major depressive disorder. • TSH could distinguish patients with abnormal glucose metabolism from those without. The high co-morbidity of abnormal glucose metabolism in depressed patients has been extensively studied, but few studies have explored abnormal glucose metabolism in young patients with major depressive disorder (MDD). This study aimed to examine the prevalence and clinical correlates of abnormal glucose metabolism in young patients with first-episode medication-naïve (FEMN) MDD. A cross-sectional study was conducted on 1289 young Chinese outpatients with FEMN MDD. All subjects were assessed on the Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale (HAMA), Positive and Negative Syndrome Scale, and their sociodemographic information was collected, and blood pressure, blood glucose, lipid and thyroid hormone levels were measured. The prevalence of abnormal glucose metabolism was 12.57% in young FEMN MDD outpatients. Thyroid stimulating hormone (TSH) levels and HAMA scale scores were associated with fasting blood glucose levels in patients with FEMN MDD (P <0.05), and TSH could differentiate patients with abnormal normal glucose metabolism from those without abnormal glucose metabolism (Area Under Curve of 0.774). Our study showed a high prevalence of comorbid glucose metabolism abnormalities in young FEMN MDD outpatients. TSH may be a promising biomarker of abnormal glucose metabolism in young patients with FEMN MDD. [ABSTRACT FROM AUTHOR]

Quetiapine (QUE) and repetitive transcranial magnetic stimulation (rTMS) have been considered to be possible monotherapies for depression or adjunctive therapies for the treatment of the resistant depression, but the underlying mechanisms remain unclear. The present study aimed to assess the effects of combined QUE and rTMS treatment on depressive-like behaviors, hippocampal proliferation, and the in vivo and in vitro expressions of phosphorylated extracellular signal-regulated protein kinase (pERK1/2) and brain-derived neurotrophic factor (BDNF) in male Sprague–Dawley rats. The administration of QUE and rTMS was determined not only to reverse the depressive-like behaviors of rats exposed to chronic unpredictable stress (CUS) but also to restore the protein expressions of pERK1/2 and BDNF and cell proliferation in the hippocampus. Additionally, QUE and rTMS promoted the proliferation and increased the expression of pERK1/2 and BDNF in hippocampal-derived neural stem cells (NSCs), and these effects were abolished by U0126. Taken together, these results suggest that the antidepressive-like effects of QUE and rTMS might be related to the activation of the BDNF/ERK signaling pathway and the up-regulation of cell proliferation in the hippocampus. [ABSTRACT FROM AUTHOR]