ABSTRACT Purpose Growing evidence implicates gut microbiota dysbiosis in social anxiety disorder (SAD), yet direct causal evidence remains limited. This study investigated whether fecal microbiota transplantation (FMT) from individuals with SAD was associated with general anxiety‐like behaviors and accompanying gut microbial and predicted metabolic alterations in mice. Methods Fecal samples were collected from five patients diagnosed with SAD and five matched healthy controls and transplanted into antibiotic‐treated mice. Anxiety‐like behaviors were evaluated using the open‐field test (OFT) and elevated‐plus maze test (EPMT). Gut microbiota composition was assessed by 16S rRNA gene sequencing, microbial functional potential was inferred using PICRUSt2, and plasma tryptophan‐pathway metabolites were quantified. Results Mice receiving SAD microbiota (SAD group) showed general anxiety‐like behaviors, characterized by more time spent in the periphery of the OFT and fewer entries and less time in the open arms of the EPMT compared to mice receiving healthy control microbiota (control group). Although α‐diversity did not differ significantly, β‐diversity was distinct between groups. The SAD group showed enrichment of Bacteroidota/Bacteroidales‐related bacteria (e.g., Muribaculum), whereas the control group had higher abundance of butyrate producers (e.g., Butyricimonas). Functional prediction indicated lower predicted abundance of selected DNA‐repair and biosynthetic pathways in the SAD group. Plasma tryptophan levels were nominally lower in the SAD group. Conclusions These findings suggest that specific gut microbiota alterations and predicted functional pathway changes in individuals with SAD may be associated with anxiety‐related behavioral phenotypes, supporting the gut microbiome as a potential contributing factor to the pathophysiology of SAD.

Major depressive disorder is projected to become the leading contributor to mental illness by 2030. While resting-state functional magnetic resonance imaging (rs-fMRI) has emerged as a non-invasive solution for depression detection, two significant challenges remain. First, due to medical data privacy regulations and the high costs associated with acquiring the necessary equipment, individual medical institutions struggle to obtain sufficient annotated data. Second, domain shifts, caused by discrepancies in scanner parameters and acquisition protocols across multi-center datasets, significantly hinder model generalization. To address these challenges, we propose a federated domain adaptation (FDA) method that integrates co-activation patterns and a multimodal Mamba network, termed FDA-CAPMA, for fMRI-based depression detection. Specifically, a federated learning architecture ensures both physical data isolation and patient privacy through parameter aggregation. A state-space model-based Mamba network captures cross-modal correlations between fMRI time-series features and non-imaging features. Additionally, a local maximum mean discrepancy (LMMD) module aligns source and target domain distributions in both feature and prediction spaces. Extensive experiments on the largest multi-center depression dataset (Rest-meta-MDD, 1813 participants) and ABIDE dataset, our method achieves an accuracy of 67.16%, and 65.72%, respectively. This work establishes a new paradigm for privacy-preserving depression recognition. Code will be available at: https://github.com/helang818/FDA-CAPMA/.

The gut microbiota is implicated in the pathogenesis of generalized anxiety disorder (GAD), but whether microbial differences between GAD patients with remission (R-GAD) and those with poor early treatment response (P-GAD) causally contribute to variable therapeutic outcomes remains unclear. Here, we transplanted feces from R-GAD and P-GAD patients into antibiotic-pretreated male C57BL/6 mice. P-GAD recipients showed heightened anxiety-like behaviors (reduced central zone time in open field test and shorter open-arm duration in elevated plus-maze), lower gut microbial α-diversity, and distinct β-diversity. Linear discriminant analysis effect size (LEfSe) detected 155 differentially abundant taxa. Genera enriched in R-GAD mice included Blautia, Roseburia, and Lachnospiraceae_NK4A136_group, whereas P-GAD mice were characterized by higher abundances of Bacteroides, Ileibacterium, and Allobaculum. Metabolomic analysis revealed that P-GAD mice had higher levels of neurotoxic tryptophan metabolite indoxyl-β-D-glucuronide (Indoxyl-GlcA) and lower levels of neuroprotective metabolites (indole-3-lactic acid, ILA; L-kynurenine, L-Kyn). Among 34 fatty acids, only C22:5 N3 (docosapentaenoic acid, DPA) was significantly lower in P-GAD mice. Correlation analyses further revealed that genera enriched in P-GAD mice were positively associated with pro-anxiety behaviors and neurotoxic metabolites, whereas those enriched in R-GAD mice showed the opposite trends. These findings suggest that gut microbiota from GAD patients with poor early treatment response may transmit anxiety-like phenotypes and metabolic disturbances in mice, providing a rationale for microbiota-targeted interventions in GAD.

Comorbid anxiety in adolescents with major depressive disorder (adMDD) is linked to higher suicide risk and poorer prognosis, necessitating precise screening tools. This study developed an interpretable machine learning (ML) framework using electroencephalography (EEG) biomarkers to predict anxiety symptoms in 200 adMDD (aged 12-18, drug-free for ≥ 2 weeks). Participants, stratified by Hamilton Anxiety Rating Scale (HAMA ≥ 14 for comorbid anxiety, n = 172; HAMA < 14, n = 28), underwent EEG recordings. Thirty-two EEG features (time-domain, frequency-domain, nonlinear, Hjorth, and entropy-based) were extracted, and seven machine learning models were trained and validated using 3-fold nested cross-validation. Results indicated the Light Gradient Boosting Machine (LightGBM) have superior predictive performance, with AUC value of 0.72 ± 0.05, accuracy value of 0.83 ± 0.02, precision value of 0.91 ± 0.02, recall value of 0.89 ± 0.03, F1 score of 0.90 ± 0.14, and AUPRC of 0.92 ± 0.03. In addition, SHAP analysis highlighting Normalized first difference, the ratio of Alpha to Beta, and Theta-band power as key predictors. This framework, enhanced by SHAP's global and local interpretability, identifies individualized EEG patterns for anxiety risk, offering a transparent, data-driven tool for personalized diagnostics in adMDD. These findings align with translational psychiatry goals to advance biomarker-based diagnostics in youth mental health.

BACKGROUND:Major depressive disorder (MDD) and bipolar disorder (BD) are frequently misdiagnosed due to overlapping depressive symptomatology, leading to suboptimal treatment outcomes. While lipidomics has shown promise in distinguishing these disorders, dynamic lipid alterations during treatment remain unexplored. METHODS:We conducted a prospective, paired-design lipidomic study involving 31 MDD and 30 BD patients, assessed at baseline and after 2 weeks of treatment, alongside 32 matched healthy controls (HC). Plasma lipids were profiled using liquid chromatography-mass spectrometry (LC/MS). Orthogonal partial least squares-discriminant analysis (OPLS-DA), pathway enrichment, and LASSO regression were employed to identify differential lipids and construct diagnostic panels. RESULTS:Significant differences in lipid classes were observed between MDD and HC, and between BD and HC, while differences between MDD and BD were not substantial. Notable variations in the relative contents of numerous lipid species were detected across the three groups. Alternations in lipid species within the MDD and BD groups before and after treatment were highly significant. Diagnostic lipid panels were developed to differentiate MDD from HC (13 lipids), BD from HC (12 lipids), and MDD from BD (13 lipids) using Venn diagrams and Lasso regression models. CONCLUSIONS:This first paired follow-up lipidomics study in MDD and BD reveals dynamic lipid alterations early in treatment and proposes highly discriminative lipid panels. These findings underscore the role of lipid dysregulation in affective disorders and suggest potential biomarkers for differential diagnosis.

Major depressive disorder (MDD) is a leading cause of disability worldwide, and current antidepressants are limited by delayed onset and incomplete efficacy. Esketamine produces antidepressant effects more rapidly than conventional treatments, but its underlying mechanisms remain unclear. We examined whether cannabinoid type 1 receptor (CB1R) signaling is associated with hippocampal mitochondrial biogenesis-related changes following esketamine treatment in a chronic variable stress (CVS) mouse model.Mice underwent 21 days of CVS and received a single intraperitoneal injection of esketamine (15 mg/kg) 24 h before behavioral testing. Hippocampal CB1R, nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (TFAM), and total cytochrome C expression were assessed by Western blotting. Additional groups received the CB1R antagonists AM251 or SR141716A before esketamine administration.CVS induced depressive-like behavioral changes in the forced swim, tail suspension, and novelty-suppressed feeding tests. These effects were accompanied by reduced hippocampal CB1R, NRF1, and TFAM expression and altered total cytochrome c expression. Esketamine reversed the behavioral abnormalities and normalized these molecular changes. Pretreatment with either CB1R antagonist prevented both the behavioral and molecular effects of esketamine.These findings indicate that the antidepressant-like effects of esketamine observed 24 h after administration are associated with CB1R-dependent changes in hippocampal mitochondrial biogenesis-related protein expression. Further studies using direct mitochondrial functional assays and loss-of-function approaches are needed to establish causality.

High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) is an effective treatment for depression, but its synaptic mechanisms remain incompletely understood. Using a chronic unpredictable mild stress (CUMS) mouse model, we investigated whether cannabinoid receptor 1 (CB1R) signaling in distinct neuronal populations contributes to the amelioration of depressive-like behaviors by HF-rTMS through modulation of prefrontal inhibitory synaptic transmission. Behavioral assessments were combined with whole-cell patch-clamp recordings of spontaneous inhibitory postsynaptic currents (sIPSC) in prefrontal cortex pyramidal neurons, along with systemic pharmacological CB1R blockade (AM281) and conditional knockout mice with deletion of CB1R in glutamatergic (vGlut1-CB1R-KO) or GABAergic (GAD2-CB1R-KO) neuronal populations. sIPSC frequency and amplitude were analyzed as indirect indices of presynaptic release and postsynaptic receptor function, respectively. HF-rTMS ameliorated CUMS-induced depressive-like behaviors and partially normalized sIPSC alterations (frequency and amplitude), which were attenuated by AM281. In vGlut1-CB1R-KO mice, baseline sIPSC frequency was reduced and half-width prolonged; CUMS exacerbated these alterations and induced anhedonia/anxiety, yet HF-rTMS failed to rescue any behavioral or synaptic changes. In contrast, GAD2-CB1R-KO mice exhibited baseline anxiety-like behavior accompanied by increased sIPSC frequency, consistent with loss of presynaptic CB1R-mediated suppression of GABA release, but showed attenuated-CUMS-induced depressive-like behaviors,; HF-rTMS partially modulated postsynaptic function (increased amplitude, accelerated kinetics). These findings suggest that glutamatergic CB1R signaling contributes to the ability of HF-rTMS to modulate presynaptic inhibitory function. Meanwhile, GABAergic CB1R ablation is accompanied by reduced behavioral vulnerability to chronic stress and may shift HF-rTMS actions toward potential postsynaptic modulatory processes. Collectively, these observations implicate cell-type-specific CB1R signaling in shaping the synaptic responses of prefrontal inhibitory circuits to HF-rTMS.

ABSTRACT Purpose Repetitive transcranial magnetic stimulation (rTMS) represents a potential clinical tool in treating bipolar disorder (BD). However, the intervention of rTMS combined with pharmacotherapy on the plasma fatty acids (FAs) in patients with bipolar depression has not been reported yet. Method In this study, we assessed the clinical symptoms and evaluated plasma FAs from 30 inpatients with bipolar depression at baseline phase (BD group), after 2 weeks of treatment with rTMS combined with quetiapine and mood stabilizer (BD‐2w group), and 32 healthy controls (HCs). Finding We found that acetic acid, propionic acid, isovaleric acid, isobutyric acid, and valeric acid, as well as levels of total short‐chain fatty acids (SCFAs), were decreased in both BD and BD‐2w groups, and levels of several medium‐ and long‐chain fatty acids (MLCFAs) were altered in BD when compared with HC. Moreover, 2 weeks of treatment increased the levels of various MLCFAs. Finally, we developed combinational FAs panels that could distinguish BD from HC (area under the curve [AUC] = 0.961), BD‐2w from HC (AUC = 0.978), and BD from BD‐2w (AUC = 0.891) effectively. Conclusion These findings might provide a basis for developing diagnostic methods and reveal the potential relationship between bipolar depression and plasma FAs.

OBJECTIVE:This study investigated the role of endocannabinoid (eCB) signaling in anxiety-like behaviors associated with a PTSD mouse model (SPS&S), focusing on oxidative stress and inflammation. METHODS:We examined expression of eCB-related proteins (Cannabinoid receptor type 1, CB1 Receptor; NAPE-specific phospholipase D, NAPE-PLD; Fatty acid amide hydrolase, FAAH; and Monoacylglycerol lipase, MAGL) and inflammatory markers (IL-1β, caspase-1) in the mPFC, hippocampus, and amygdala of SPS&S-exposed mice. Plasma oxidative stress markers (MDA, SOD, ROS) and cytokines (IL-1β, IL-6, TNF-α, COX-2) were measured by ELISA. The CB1 receptor agonist WIN 55,212-2 or vehicle was administered systemically, then anxiety-like behaviors and conditioned fear were assessed. RESULTS:SPS&S exposure induced significant anxiety-like behaviors and increased freezing in fear tests. It decreased CB1 receptor and NAPE-PLD expression while increasing FAAH and MAGL levels in all examined brain regions, alongside elevated IL-1β and caspase-1. Plasma oxidative stress and inflammatory cytokines were also elevated. WIN 55,212-2 administration mitigated anxiety-like behaviors but not conditioned fear responses. Crucially, it normalized the elevated plasma oxidative stress and inflammatory cytokine levels. CONCLUSION:SPS&S disrupts eCB signaling and increases neuroinflammation and peripheral oxidative stress/inflammation. Activation of CB1 receptor alleviates PTSD-associated anxiety-like behaviors and normalizes peripheral oxidative/inflammatory biomarkers, highlighting the critical involvement of eCB-related oxidative stress and inflammatory pathways. Targeting the eCB system represents a potential therapeutic strategy for anxiety symptoms in PTSD.

BACKGROUND:Intestinal dysbacteriosis is frequently implicated in generalized anxiety disorder (GAD). However, the molecular mechanisms and functional changes of the gut-brain axis in GAD remain largely unexplored. METHODS:We investigated anxiety-like behaviors, gut microbiota changes, brain region-specific endocannabinoid (eCB) system alterations, including the expression of cannabinoid type 1 (CB1R), monoacylglycerol lipase (MAGL), and fatty acid amide hydrolase (FAAH) in the hippocampus (Hip), prefrontal cortex (PFC), and amygdala (Amy), as well as plasma medium- and long-chain fatty acids (MLCFAs) in a mouse model of chronic restraint stress (CRS) and antibiotic-treated mice receiving fecal microbiota transplantation from GAD patients (FMT-GAD). Additionally, we assessed the impact of FMT-GAD on anxiety-like behavior in systemic CB1R/FAAH/MAGL knockout mice. RESULTS:CRS induced anxiety-like behaviors, suppressed eCB signaling in the brain, and altered the gut microbiota and plasma MLCFA composition in mice. FMT-GAD-treated mice exhibited anxiety-like behaviors, increased FAAH expression in the Hip and Amy, and MAGL expression in the Hip, while reducing CB1R expression in the Hip. FMT-GAD was associated with decreased plasma polyunsaturated fatty acids (PUFAs) and reduced microbiome function for fatty acid biosynthesis. Notably, FMT-GAD intensified anxiety-like behaviors in CB1R-KO mice but failed to induce anxiety-like behaviors in MAGL-KO and FAAH-KO mice. CONCLUSIONS:This study demonstrates that the interplay between the gut microbiota and the eCB system modulates GAD-related anxiety-like behaviors.

The psychological symptoms of temporomandibular joint (TMJ) ankylosis were similar to that of depressive disorder, but there were no relevant evidences to confirm that the humans or animals with TMJ ankylosis had depressive disorder. The aim of this study was to investigate the association between TMJ ankylosis and depressive disorder in the rat model. Thirty 3-week-old male Sprague–Dawley (SD) rats were used in this study. The damage of TMJ complexes and narrowed joint space were performed in the unilateral TMJ of test group to induce TMJ bony ankylosis (experimental side). The other TMJ of test group underwent a sham operation (sham side). The TMJs of control group did not undergo any operations. At 8 weeks postoperatively, behavioral tests, body weight, passive maximum mouth opening (PMMO), and TMJ morphological features were evaluated, and the hippocampuses were analyzed using western blotting and immunocytochemistry. The data was compared between the test group and control group by independent t-test, between the experimental side and sham side by paired t-test. The correlations between PMMO/area of bony fusion and duration of immobility, sucrose preference, CB1 receptor protein, mean optical density of CB1 receptor protein, and the number of BrdU-positive cell were evaluated using linear regression analysis. The level of significance was 0.05. In the test group, the traumatic TMJ complexes with narrowed joint space developed TMJ bony ankylosis, the area of bony mass of experimental side (21.26 mm2) was larger than that of sham side (1.73 mm2) (p < 0.001). There were significant difference with the sucrose preference (test group: 0.36, control group: 0.76, p < 0.001), duration of immobility (test group: 127.36 s, control group: 59.41 s, p < 0.001), body weight (test group: 156.70 g, control group: 270.06 g, p < 0.001), PMMO (test group: 9.98 mm, control group: 28.79 mm, p < 0.001), CB1 receptor protein (test group: 41.00

AbstractBackgroundGut dysbiosis has been established as a characteristic of schizophrenia (SCH). However, the signatures regarding SCH patients with prominent negative symptoms (SCH‐N) in young adults have been poorly elucidated.MethodsStool samples were obtained from 30 young adults with SCH‐N, 32 SCH patients with prominent positive symptoms (SCH‐P) along with 36 healthy controls (HCs). Microbial diversity and composition were analyzed by 16S rRNA gene sequencing. Meanwhile, psychiatric symptoms were assessed by the positive and negative syndrome scale (PANSS).ResultsThere is a significant difference in β‐diversity but not α‐diversity indexes among the three groups. Moreover, we found a higher abundance of Fusobacteria and Proteobacteria phyla and a lower abundance of Firmicutes phyla in SCH‐N when compared with HC. Besides, we identified a diagnostic potential panel comprising six genera (Coprococcus, Monoglobus, Prevotellaceae_NK3B31_group, Escherichia‐Shigella, Dorea, and Butyricicoccus) that can distinguish SCH‐N from HC (area under the curve = 0.939). However, the difference in microbial composition between the SCH‐N and SCH‐P is much less than that between SCH‐N and the HC, and SCH‐N and SCH‐P cannot be effectively distinguished by gut microbiota.ConclusionThe composition of gut microbiota was changed in the patients with SCH‐N, which may help in further understanding of pathogenesis in young adults with SCH‐N.

Mounting evidence has identified the rapid and sustained antidepressive and anxiolytic-like effects of esketamine. However, the underlying mechanism of this no-monoamine target rapid-onset antidepressant is still underexplored. Immune-inflammatory pathways and cell-mediated immune activation, mainly including inflammatory cytokines in plasma, play a pivotal role in the pathogenesis of major depressive disorder and are also a potential therapeutic target for MDD. The current study was designed to clarify the role of esketamine on the expression of plasma cytokines in a depressive-like model introduced by chronic variable stress (CVS). In this study, a 21-day consecutive CVS protocol was applied to produce depressive- and anxiety-like behaviors. After the single dose or 7-day repeated administration of esketamine or fluoxetine, the depressive- and anxiety-like behaviors and the expression of inflammatory cytokines in plasma were examined. Both a single dose of esketamine and 7-days repeated fluoxetine administration elicited anti-depressive and anxiolytic effects in mice exposed to CVS. Additionally, CVS produced significant changes in the plasma inflammatory factors, notably increasing the expression of IL-1β, IL-6, IL-8, IL-17A, TNFα, IL-4, IL-9, IL-24, IL-37, IFN-β, and CXCL12, while reducing IL-10 and IL-33. With the administration of esketamine and fluoxetine, CVS-produced inflammatory disturbances were partially normalized. Together, our findings provide a novel insight that acute esketamine treatment could rescue CVS-produced depressive-like and anxiety-like behaviors in mice by normalizing the expression of inflammatory cytokines; this effect was similar to the repeated administration of fluoxetine. These results contributed to the understating of rapid anti-depressant effects elicited by esketamine.

Bilateral repetitive transcranial magnetic stimulation (B-rTMS) has been largely used in the treatment of major depressive disorder (MDD). Nonetheless, information on the acute treatment by B-rTMS combined with antidepressants (ADs) on the plasma fatty acids in MDD is limited. The present study focused on depressive symptoms; Plasma was obtained from 27 adult patients with MDD at baseline phase (MDD), after 2 weeks of treatment (MDD-2w), and 27 healthy controls (HC). Meanwhile, we evaluated the composition of short-chain fatty acids (SCFAs) and medium-and long-chain fatty acids (MLCFAs) in the plasma. Consequently, the levels of Isobutyric acid, Caproic acid, and Propionic acid were low both in the MDD and MDD-2w groups and negatively correlated with the scores of HAMD and HAMA. Besides, minimal changes were observed between the MDD and HC groups, whereas significant MLCFA levels were high in the MDD-2w group. Moreover, we developed combined panels that could effectively differentiate MDD from HCs (AUC=0.99), MDD-2w from HC (AUC=0.983), and MDD from MDD-2w (AUC=0.852). These findings may provide a reference for the use of B-rTMS combined with ADs against the acute phase of depressive episodes and shed light on the relationship between plasma FAs and MDD.

The iMeta Conference 2024 provides a platform to promote the development of an innovative scientific research ecosystem for microbiome and One Health. The four key components - Technology, Research (Biology), Academic journals, and Social media - form a synergistic ecosystem. Advanced technologies drive biological research, which generates novel insights that are disseminated through academic journals. Social media plays a crucial role in engaging the public and facilitating scientific communication, thus amplifying the impact of research. Together, these elements create a self-sustaining loop that fosters continuous innovation and collaboration in the field of bioinformatics, biotechnology and microbiome research.

Background: 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). Objective: 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). Methods: 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. Results: 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. Conclusions: 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.

Major depressive disorder (MDD) and schizophrenia (SCH) are common and severe mental disorders that are mainly diagnosed depending on the subjective identification by psychiatrists. Finding potential objective biomarkers that can distinguish these two diseases is still meaningful. In the present study, we investigate the differences in plasma inflammatory cytokines and short-chain fatty acids (SCFAs) among patients with MDD (n = 24) and SCH (n = 24), and gender- and age-matched healthy controls (HC, n = 27) and identify potential plasma biomarkers. We found that the concentrations of pro-inflammatory cytokines were increased, whereas the anti-inflammatory cytokines were decreased in both MDD and SCH. Meanwhile, except for an increase in 4-Methylvaleric acid, other SCFAs with statistical differences were reduced in both MDD and SCH. Moreover, potential biomarker panels were developed that can effectively discriminate MDD from HC (AUC = 0.997), SCH from HC (AUC = 0.999), and from each other (MDD from SCH, AUC = 0.983). These data suggest that alterations in plasma cytokines and SCFAs might be one of the potential features for distinguishing MDD and SCH. Chinese Clinical Trial Registry: ChiCTR2100051243, registration date: 2021/09/16.

Introduction Post-traumatic stress disorder (PTSD) is a prevalent and severe psychiatric disorder. Repetitive transcranial magnetic stimulation (rTMS) targeting the dorsolateral prefrontal cortex provides limited relief for symptoms of PTSD. This study will be conducted to validate the efficacy of MRI-guided rTMS in targeting the sites most closely associated with the amygdala for patients with PTSD. We hypothesise that the intervention will improve clinical symptoms by decreasing amygdala activity in patients.Methods and analysis A randomised, double-blind, sham-controlled trial will be conducted. Forty-eight eligible patients with PTSD will be randomly assigned to receive either active or sham MRI-guided rTMS for 10 consecutive days after the initial MRI scans. MRI scans will be recollected at the end of the intervention. Clinical assessments will be performed at baseline, treatment day 5, treatment day 10, and 2 weeks, 4 weeks, 8 weeks after completion of the intervention to monitor changes in clinical symptoms. The primary assessment outcome is the change in PTSD symptoms between baseline and treatment day 10, as measured by the PTSD Checklist for DSM-5. Repeated measures analysis of variance will be performed using statistical software SPSS V.26.0. The significance level will be set at 0.05.Ethics and dissemination Ethical approval has been obtained from the Ethics Committee of Xijing Hospital in Xi'an, China (KY20222176-X-1), and the trial has been registered on ClinicalTrials.gov. The findings of this trial will be disseminated at academic conferences or published in peer-reviewed scientific journals.Trial registration number NCT05544110.

抑郁症是危害人类健康的主要精神疾病之一.现有的单胺类假说并不能完全解释抑郁症的发病机制,以此为靶点的抗抑郁药物起效速度慢、部分患者缺乏疗效.线粒体是存在于真核细胞中的多功能细胞器,在能量产生、细胞凋亡、氧化应激、神经发生等过程中发挥关键作用.近年来,大量的证据表明线粒体功能障碍和抑郁症发病机制关系密切.在本文中,我们对线粒体能量代谢障碍与抑郁症关系的研究进展进行综述,包括线粒体DNA损伤、线粒体和炎症及神经发生之间的关联、线粒体靶向治疗抑郁症的潜能等,并总结了现有抗抑郁治疗与线粒体功能调控相关的进展,从而为深入理解抑郁症发病机制以及筛选靶向线粒体的新型治疗策略提供参考.

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.