Gut microbial, mainly bacterial dysbiosis, has been demonstrated in patients with schizophrenia (SCH). However, the signatures and differences of minority gut microbiota in SCH, such as archaea and fungi, have been poorly addressed. We obtained stool samples from 61 SCH patients and 69 healthy controls (HC), and analyzed the compositional and functional alterations of gut archaea, fungi, and bacteria using metagenomic shotgun sequencing (MSS). Additionally, we developed potential biomarkers to distinguish SCH from HC. SCH patients showed significantly lower archaeal α-diversity compared with that of HC. Whereas there were significant differences between SCH and HC in β-diversity at the species level of archaea, fungi and bacteria. Meanwhile, the functional differences between the two groups were concentrated in glucose, lipid and amino acid metabolic pathways. Furthermore, we established potential diagnostic archaeal (9 species, AUC = 0.73), fungal (8 species, AUC = 0.69), and bacterial (22 species, AUC = 0.74) microbiomes for differentiating SCH patients from HC. This study describes a more comprehensive understanding of abnormal gut microbiome in SCH and might provide candidate targets for the development of a microbe-based diagnosis for SCH. Chinese Clinical Trial Registry: ChiCTR2000032118, registration date: 2020/04/20.

Background Although the relationship between negative symptoms and cognitive deficits in schizophrenia has been extensively investigated, there remained limited research on the differential clinical factors influencing cognitive function in chronic schizophrenia patients with distinct symptom profiles. This study aimed to investigate the clinical correlates of cognitive dysfunction in chronic schizophrenia patients categorized by predominant symptom manifestations. Methods In this cross-sectional study, 409 Chinese patients with chronic schizophrenia underwent comprehensive assessment using the following standardized instruments: the Positive and Negative Syndrome Scale (PANSS), the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), the Insomnia Severity Index (ISI), and the Global Deterioration Scale (GDS). Sociodemographic data were also collected. Results Patients with prominent negative symptoms (SCZ-N) had significantly lower RBANS total scores compared to those with dominant positive symptom (SCZ-P). Spearman’s correlation analysis revealed that in the SCZ-N group, PANSS total score and negative symptom score were significantly negatively correlated with RBANS total score and all 5 subdomain scores (all p < 0.01). In contrast, in the SCZ-P group, significant negative correlations were mainly observed between PANSS score, negative symptom score, RBANS total score and attention score (all p < 0.01). Multiple linear regression analysis further showed that cognitive impairment was associated with multiple factors, including years of education, gender, illness duration, PANSS general psychopathology score, and GDS assessment levels in the SCZ-N group. In the SCZ-P group, cognitive dysfunction was primarily associated with GDS assessment levels and negative symptom score. Conclusions The findings of this study indicate that the severity of negative symptoms is a strong correlate of cognitive impairment in patients with chronic schizophrenia. These results collectively indicate that targeting negative symptoms is paramount for effective cognitive management in chronic schizophrenia.

Background Invasive vagus nerve stimulation therapy has been approved for the adjunctive treatment of treatment-resistant depression,which may contribute to the anti-inflammatory properties of vagus nerve stimulation(VNS),whereas the efficacy of non-invasive transcutaneous cervical vagus nerve stimulation(tcVNS)in treating major depressive disorder(MDD)and its impact on plasma inflammatory factors remain unclear.Objective To observe the effect of escitaloprom combined with tcVNS on the status of depression,anxiety and sleep quality as well as the plasma levels of interleukin-6(IL-6)and interleukin-10(IL-10)in MDD patients,in order to provide references for the recovery and treatment of MDD patients.Methods From August 21,2019 to April 17,2024,45 patients who met the diagnostic criteria for MDD in the Diagnostic and Statistical Manual of Mental Disorders,fifth edition(DSM-5)were recruited from the psychosomatic outpatient clinic of the First Affiliated Hospital of Air Force Military Medical University.Subjects were divided into study group(n=23)and control group(n=22)using random number table method.All patients were treated with escitalopram.On this basis,study group added a 30-minute tcVNS therapy once a day for 4 weeks.While control group was given corresponding sham stimulation,and the duration of each stimulation lasted 30 seconds.Before and after 4 weeks of treatment,Hamilton Depression Scale-17 item(HAMD-17)was used to assess depressive symptoms,and HAMD-17 anxiety/somatization subfactor and insomnia subfactor were used to assess patients' anxiety/somatization symptoms and sleep quality.Levels of plasma IL-6 and IL-10 were measured by enzyme-linked immunosorbent assay(ELISA).Results The generalized estimating equation model yielded a significant time effect for HAMD-17 total score,anxiety/somatization subfactor score and insomnia subfactor score in both groups(Wald χ2=315.226,495.481,82.420,P<0.01).After 4 weeks of treatment,HAMD-17 total score and anxiety/somatization subfactor score of study group were lower than those of control group,with statistically significant differences(Wald χ2=4.967,32.543,P<0.05 or 0.01),while no statistically significant difference was found in the insomnia subfactor score between two groups(Wald χ2=0.819,P=0.366).Significant time effects were reported on plasma IL-6 and IL-10 levels in both groups(Wald χ2=21.792,5.242,P<0.05 or 0.01).Compared with baseline data,a reduction in plasma IL-6 levels was detected in both groups(Wald χ2=22.015,6.803,P<0.01),and an increase in plasma IL-10 levels was reported in study group(Wald χ2=5.118,P=0.024)after 4 weeks of treatment.Conclusion Escitalopram combined with tcVNS therapy is effective in improving depressive symptoms,anxiety/somatization symptoms and sleep quality in patients with MDD.Additionally,it helps reduce plasma IL-6 levels and increase IL-10 levels.

BackgroundDepression 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.MethodsIn 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.ResultsAfter 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.LimitationsOnly rodent models of depression were used, and human samples were not included.ConclusionsThe 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.

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.

High suicide risk represents a serious problem in patients with major depressive disorder (MDD), yet treatment options that could safely and rapidly ameliorate suicidal ideation remain elusive. Here, we tested the feasibility and preliminary efficacy of the Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) in reducing suicidal ideation in patients with MDD. Thirty-two MDD patients with moderate to severe suicidal ideation participated in the current study. Suicidal ideation and depression symptoms were assessed before and after 5 days of open-label SAINT. The neural pathways supporting rapid-acting antidepressant and suicide prevention effects were identified with dynamic causal modelling based on resting-state functional magnetic resonance imaging. We found that 5 days of SAINT effectively alleviated suicidal ideation in patients with MDD with a high response rate of 65.63%. Moreover, the response rates achieved 78.13% and 90.63% with 2 weeks and 4 weeks after SAINT, respectively. In addition, we found that the suicide prevention effects of SAINT were associated with the effective connectivity involving the insula and hippocampus, while the antidepressant effects were related to connections of the subgenual anterior cingulate cortex (sgACC). These results show that SAINT is a rapid-acting and effective way to reduce suicidal ideation. Our findings further suggest that distinct neural mechanisms may contribute to the rapid-acting effects on the relief of suicidal ideation and depression, respectively.

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.

Functional nanomaterials have emerged as versatile nanotransducers for wireless neural modulation because of their minimal invasion and high spatiotemporal resolution. The nanotransducers can convert external excitation sources (e.g., NIR light, X-rays, and magnetic fields) to visible light (or local heat) to activate optogenetic opsins and thermosensitive ion channels for neuromodulation. The present review provides insights into the fundamentals of the mostly used functional nanomaterials in wireless neuromodulation including upconversion nanoparticles, nanoscintillators, and magnetic nanoparticles. We further discussed the recent developments in design strategies of functional nanomaterials with enhanced energy conversion performance that have greatly expanded the field of neuromodulation. We summarized the applications of functional nanomaterials-mediated wireless neuromodulation techniques, including exciting/silencing neurons, modulating brain activity, controlling motor behaviors, and regulating peripheral organ function in mice. Finally, we discussed some key considerations in functional nanotransducer-mediated wireless neuromodulation along with the current challenges and future directions.

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.

目的 观察抑郁症患者肠道菌群移植对小鼠行为及海马内源性大麻素(eCB)的影响.方法 将健康受试者和抑郁症患者的肠道菌群移植给"伪无菌"小鼠,通过糖水偏好实验、旷场实验以及悬尾实验评估其抑郁样行为,并检测海马eCB相关分子的表达水平.①模型小鼠的制备:通过灌胃的方法使用"鸡尾酒"抗生素清除小鼠原有的肠道菌群,连续灌胃14 d,制备"伪无菌"小鼠模型;最后一次抗生素灌胃结束48 h后,将小鼠随机分为对照组(n=6)和抑郁组(n=10),每周一、三、五分别对各组小鼠进行粪菌移植,持续3周,制备"人源化"小鼠模型;②行为学测试:粪菌移植结束24 h后进行糖水偏好实验、旷场实验和悬尾实验以评估小鼠的抑郁样行为;③行为学测试结束24 h后处死动物,通过Western blotting法检测小鼠海马组织eCB相关分子的表达情况.结果 ①与对照组比较,抑郁组抑郁样行为表现显著,具体表现为旷场实验中抑郁组小鼠进入中心区次数、中心区运动距离、运动总距离、中心区停留时间比均显著降低(P＜0.01),糖水偏好率显著下降(P＜0.05),悬尾不动时间显著增长(P＜0.01).②Western blotting结果显示,与对照组比较,抑郁组CB1R、NAPE-PLD、DAGLα蛋白表达均显著下调,差异具有统计学意义(P＜0.05).③海马NAPE-PLD和DAGLα的表达水平与小鼠进入中心区次数、中心区运动距离、中心区停留时间比和糖水偏好率均呈正相关(均P＜0.05),而且DAGLα、NAPE-PLD表达水平与悬尾不动时间均呈负相关(均P＜0.05).结论 抑郁症患者肠道菌群可能通过调节海马eCB相关分子诱导小鼠产生抑郁样行为.

Backgrounds: 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-naive (FEMN) MDD.Methods: A cross-sectional study was conducted on 1289 young Chinese outpatients with FEMN MDD. All sub-jects 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. Results: 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 meta-bolism from those without abnormal glucose metabolism (Area Under Curve of 0.774).Conclusions: 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.

目的:探讨广泛性焦虑障碍(GAD)患者血清25-羟维生素D[25(OH)D]、维生素B12(VB12)与认知功能和临床疗效的关系.方法:选择2018年4月～2022年6月期间空军军医大学第一附属医院心理科门诊收治的186例GAD患者作为GAD组.另选取同期于我院体检健康的志愿者120例作为对照组.采用威斯康星卡片分类测验(WCST)评估并对比两组患者的认知功能,检测并对比两组患者的血清25(OH)D、VB12水平.采用Pearson相关性分析血清25(OH)D、VB12与认知功能的相关性.GAD组给予常规治疗,按照治疗效果分为有效组和无效组,对比有效组和无效组在治疗前后血清25(OH)D、VB12水平变化.结果:GAD组的血清25(OH)D、VB12水平低于对照组(P＜0.05).对照组完成总分类数、正确反应数、总反应数均多于GAD组,错误应答数、持续性错误数少于GAD组(P＜0.05).Pearson相关性分析结果显示,血清25(OH)D、VB12水平与错误应答数、持续性错误呈负相关;而与总分类数、正确反应数、总反应数呈正相关(P＜0.05).186例患者中,痊愈36例,疗效显著53例,有效62例,无效35例.按照治疗情况将患者分为有效组(n=151)和无效组(n=35).两组治疗后血清25(OH)D、VB12水平均升高,且有效组高于对照组(P＜0.05).结论:GAD患者的25(OH)D、VB12水平下降,且与其认知功能下降有关,25(OH)D、VB12水平较低的GAD患者其治疗效果也相对更差,提示临床诊疗过程中应密切关注患者25(OH)D、VB12水平以制定相应的治疗措施.

Repetitive transcranial magnetic stimulation (rTMS) has been widely used in treating schizophrenia (SCH). However, the effects of the low frequency of rTMS combined with antipsychotics on the gut microbiome in chronic SCH have been poorly investigated. In the present study, psychiatric symptoms were assessed and the stool samples obtained from 33 adult patients with chronic SCH (at baseline phase), 27 after 2 weeks of treatment (rTMS combined with risperidone, SCH-2W), and 37 healthy controls (HC) were analyzed by 16S rRNA gene sequencing. We found that the reduction of phylum Proteobacteria, family Enterobacteriaceae and genera Escherichia-Shigella as well as the increase of genera norank_f_Lachnospiraceae might be related to the antipsychotic effect of rTMS combined with risperidone. These findings indicate that the brain-gut-microbiota axis might be involved in the therapeutic effect of rTMS combined with antipsychotic drugs.

BACKGROUND:Previous sleep electroencephalography studies have detected abnormalities in sleep architecture and sleep spindle deficits in schizophrenia (SCZ), but the consistency of these results was not robust, which might be due to the small sample size and the influence of clinical factors such as the various medication therapies and symptom heterogeneity. This study aimed to regard auditory verbal hallucinations (AVHs) as a pointcut to downscale the heterogeneity of SCZ and explore whether some sleep architecture and spindle parameters were more severely impaired in SCZ patients with AVHs compared with those without AVHs.METHODS:A total of 90 SCZ patients with AVHs, 92 SCZ patients without AVHs, and 91 healthy control subjects were recruited, and parameters of sleep architecture and spindle activities were compared between groups. The correlation between significant sleep parameters and clinical indicators was analyzed.RESULTS:Deficits of sleep spindle activities at prefrontal electrodes and intrahemispheric spindle coherence were observed in both AVH and non-AVH groups, several of which were more serious in the AVH group. In addition, deficits of spindle activities at central and occipital electrodes and interhemispheric spindle coherence mainly manifested accompanying AVH symptoms, most of which were retained in the medication-naive first-episode patients, and were associated with Auditory Hallucination Rating Scale scores.CONCLUSIONS:Our results suggest that the underlying mechanism of spindle deficits might be different between SCZ patients with and without AVHs. In the future, the sleep feature of SCZ patients with different symptoms and the influence of clinical factors, such as medication therapy, should be further illustrated.

Lipidomics has become a pivotal tool in biomarker discovery for the diagnosis of psychiatric illnesses. However, the composition and quantitative analysis of peripheral lipids in female patients with bipolar disorder (BD) have been poorly addressed. In this study, plasma samples from 24 female patients with BD and 30 healthy controls (HCs) were analyzed by comprehensive lipid profiling and quantitative validation based on liquid chromatography-mass spectrometry. Clinical characteristics and a correlation between the level of lipid molecules and clinical symptoms were also observed. We found that the quantitative alterations in several lipid classes, including acylcarnitine, lysophosphatidylethanolamine, GM2, sphingomyelin, GD2, triglyceride, monogalactosyldiacylglycerol, phosphatidylinositol phosphate, phosphatidylinositol 4,5-bisphosphate, phosphatidylethanolamine, phosphatidylserine, and lysophosphatidylinositol, were remarkably upregulated or downregulated in patients with BD and were positively or negatively correlated with the severity of psychotic, affective, or mania symptoms. Meanwhile, the composition of different carbon chain lengths and degrees of fatty acid saturation for these lipid classes in BD were also different from those of HCs. Moreover, 55 lipid molecules with significant differences and correlations with the clinical parameters were observed. Finally, a plasma biomarker set comprising nine lipids was identified, and an area under the curve of 0.994 was obtained between patients with BD and the HCs. In conclusion, this study provides a further understanding of abnormal lipid metabolism in the plasma and suggests that specific lipid species can be used as complementary biomarkers for the diagnosis of BD in women.

Lipidomics has been established as a potential tool for the investigation of mental diseases. However, the composition analysis and the comparison of the peripheral lipids regarding adult women with major depressive depression (MDD) or bipolar depression (BPD) has been poorly addressed. In the present study, age-matched female individuals with MDD (n = 28), BPD (n = 22) and healthy controls (HC, n = 25) were enrolled. Clinical symptoms were assessed and the plasma samples were analyzed by comprehensive lipid profiling based on liquid chromatography-mass spectrometry (LC/MS). We found that the composition of lipids was remarkably changed in the patients with MDD and BPD when compared to HC or compared to each other. Moreover, we identified diagnostic potential biomarkers comprising 20 lipids that can distinguish MDD from HC (area under the curve, AUC = 0.897) and 8 lipids that can distinguish BPD from HC (AUC = 0.784), as well as 13 lipids were identified to distinguish MDD from BPD with moderate reliability (AUC = 0.860). This study provides further understanding of abnormal lipid metabolism in adult women with MDD and BPD and may develop lipid classifiers able to effectively discriminate MDD from BPD and HC.

BACKGROUND:Neural oscillations play a role in the antidepressant effects of repetitive transcranial magnetic stimulation (rTMS). However, the effects of high-frequency rTMS on the neural oscillations of the medial prefrontal cortex (mPFC) and hippocampus (HPC) and its molecular mechanism have not been fully clarified.METHODS:The depressive-like behaviours, local field potentials (LFPs) of the ventral HPC (vHPC)-mPFC, and alternations of endocannabinoid system (ECS) in the HPC and mPFC were observed after rTMS treatment. Meanwhile, depressive-like behaviours and LFPs were also observed after cannabinoid type-1 receptor (CB1R) antagonist AM281 or monoacylglycerol lipase inhibitor JZL184 injection. Moreover, the antidepressant effect of rTMS was further assessed in glutamatergic-CB1R and gamma-amino butyric acid (GABA)-ergic -CB1R knockout mice.RESULTS:Alternations of endocannabinoids and energy value and synchronisation of mPFC-vHPC, especially the decrease of theta oscillation induced by CUMS, were alleviated by rTMS. JZL184 has similar effects to rTMS and AM281 blocked the effects of rTMS. GABAergic-CB1R deletion inhibited CUMS-induced depressive-like behaviours whereas Glutaminergic-CB1R deletion dampened the antidepressant effects of rTMS.LIMITATIONS:The immediate effect of rTMS on field-potential regulation was not observed. Moreover, the role of region-specific regulation of the ECS in the antidepressant effect of rTMS was unclear and the effects of cell-specific CB1R knockout on neuronal oscillations of the mPFC and vHPC should be further investigated.CONCLUSION:Endocannabinoid system mediated the antidepressant effects and was involved in the regulation of LFP in the vHPC-mPFC of high-frequency rTMS.

INTRODUCTION:Gut microbial disturbance has been established as potential pathogenesis of mental disorders. However, the signatures and differences regarding patients with schizophrenia (SCH) or bipolar disorder (BD) in emerging adulthood as well as their subtypes have been poorly addressed.METHODS:In the present study, stool samples obtained from 63 emerging adult patients with schizophrenia (SCH), 50 with bipolar disorder (BD), and 40 healthy controls (HC) were analyzed by 16 S rRNA gene sequencing; psychiatric symptoms and psychological, social, and professional functioning were also assessed.RESULTS:We found that gut microbiota composition was remarkably changed in the patients with SCH and BD. Moreover, the distinct gut microbiome signatures and their potential function in bipolar depression (BP-D) and SCH with predominantly negative symptoms (SCH-N) as well as bipolar mania (BP-M) and SCH with predominantly positive symptoms (SCH-P) were also observed. Furthermore, we identified diagnostic potential biomarkers that can distinguish BD from HC (38 genera, AUC = 0.961), SCH from HC (32 genera, AUC = 0.962), and BD from Scheme (13 genera, AUC = 0.823). Potential diagnostic biomarkers that can distinguish BD-D from SCH-N (16 genera, AUC = 0.969) and BD-M from SCH-P (31 genera, AUC = 0.938) were also identified.CONCLUSION:This study provides further understanding of abnormal gut microbiome in emerging adulthood patients with SCH and BD and lay the potential foundation for the development of microbe-based clinical diagnosis for BD and SCH.

Objective:To explore the efficacy, safety and possible brain network mechanisms of individualized targeted robot assisted Stanford accelerated intelligent neuromodulation therapy (SAINT).Methods:This was a small-sample, open-label study including 15 depressed patients with suicidal ideation. All participants were treated with SAINT in combination with SNRIs. The stimulation target was localized to the region of the left dorsolateral prefrontal cortex (DLPFC) that showed the most negative functional connectivity with the subgenual anterior cingulate cortex (sgACC) based on fMRI data. Stimulation sessions were delivered hourly. Ten sessions were applied per day (18, 000 pulses/day) for 5 consecutive days (90, 000 pulses in total). Stimulation was delivered at 90% resting motor threshold. The changes of functional connectivity of brain networks in various brain regions before and after treatment were compared and analyzed by rest software and functional connectivity analysis based on seed points. The Beck Suicidal Ideation Scale Chinese Version (BSI-CV), HAMD 17, and MADRS were used to assess the suicidal ideation and depressive symptoms at baseline, post treatment, 15 days after treatment, and 30 days after treatment. Statistical analysis was performed using repeated measurements of ANOVA and paired t-tests. Results:(1) After 5-day treatment, individual′s BSI-CV score decreased significantly ( F=38.77, P<0.01), and their average score decreased by 11.80±1.17 (95 %CI=8.19-15.41), with a response rate of 86.67%. SAINT was well tolerated, and there were no significant side effects on individual′s cognitive function. (2) After treatment, patient′s MADRS score decreased significantly at all follow-up assessments ( F=306.97, P<0.01), and the average score decreased by 22.53±1.10 (95 %CI=19.15-25.91) after 5-day treatment, with a response rate of 93.33%. After 15 days and 30 days, the remission and response rates of treatment were 53.33%, 100.00%, 93.33% and 100.00%, respectively. (3) The functional network connectivity after individualized targeted robot assisted SAINT therapy showed significant improvement between sgACC, frontal lobe, temporal lobe, and parietal lobe. Conclusion:Individualized targeted robot assisted SAINT therapy showed satisfactory efficacy and safety in the reduction of suicidal ideation and depressive symptoms, and also improve the functional network connectivity of the injured brain network. Meanwhile, large-sample, randomized, and double-blind controlled studies are warranted to confirm the findings of the current study.

Objective:To investigate the effects of fluoxetine (Flx) on lipidomics of hippocampal tissue in chronic unpredictable stress (CUS) model rats.Methods:A total of 30 Sprague-Dawley rats were randomly divided into Sham group, CUS group and CUS+ Flx group, with 10 rats in each group. Rats in the CUS group and CUS+ Flx group were received one or two random stimuli every day for 28 days, and then they were received intraperitoneal injection of normal saline(1 ml/kg) and fluoxetine(10 mg/kg) respectively once a day for 14 days. Rats in the Sham group were maintained in their home cages for 28 days, and then received intraperitoneal injection of saline (1 ml/kg) once a day for 14 days. The sugar water preference experiment was carried out 24 hours after the last injection, and then the rats were killed to separate the rat hippocampus. The levels of lipid composition in hippocampus were detected by high performance liquid chromatography-mass spectrometry. The relative content of lipid was analyzed by Simca-p 14.1 and LipidSearch software version 4.1. SPSS 19.0 was used for statistical analysis. One-way ANOVA or Kruskal-Wallis test was used for comparison among groups, and Bonferroni test was used for post-hoc test. Pearson correlation or Spearman correlation was used to analyze the correlation between behavioral indexes and lipid molecular level in hippocampus.Results:There was significant difference in sugar preference test among the three groups ( F=12.830, P<0.001). The percentage of sucrose intake of rats in CUS group ((43.57±12.38)%) was significantly lower than those in Sham group ((67.09±11.81)%) and CUS+ Flx group ((62.74±8.58)%) (both P<0.05). Ninety five differential lipid molecules were screened among the three groups by lipidomic analysis, mainly distributed in glycerophospholipids and sphingolipids. Among them, levels of PE (34∶1e)+ H( r=-0.477), PE(18∶1p/20∶1)+ H( r=-0.433), PE(18∶1/18∶1)+ Na( r=-0.603), PE(36∶2p)-H( r=-0.382), PE(16∶0/20∶4)-H( r=-0.464), PE(18∶0/18.2)-H( r=-0.482), PE(16∶0e/22∶6)-H( r=-0.514), PE(18∶1/20∶4)-H( r=-0.511) and CerG1 (d18∶2/24∶0+ O)+ H( r=-0.490) were negatively correlated with sucrose preference rate (all P<0.05), whereas levels of PE (42∶6p)+ Na( r=0.379), PE(34∶0p)-H( r=0.397) and SM (d22∶1/16.0)+ HCOO( r=0.388) were positively correlated with sucrose preference rate (all P<0.05). Conclusion:Flx improves the depressive-like behavior of CUS model rats, which may be related to the regulation of hippocampal glycerophospholipid and sphingolipid metabolism.