Background: Total white blood cell count (TWBCc), an index of chronic and low-grade inflammation, is associated with clinical symptoms and metabolic alterations in patients with schizophrenia. The effect of antipsychotics on TWBCc, predictive values of TWBCc for drug response, and role of metabolic alterations require further study. Methods: Patients with schizophrenia were randomized to monotherapy with risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone, perphenazine or haloperidol in a 6-week pharmacological trial. We repeatedly measured clinical symptoms, TWBCc, and metabolic measures (body mass index, blood pressure, waist circumference, fasting blood lipids and glucose). We used mixed-effect linear regression models to test whether TWBCc can predict drug response. Mediation analysis to investigate metabolic alteration effects on drug response. Results: At baseline, TWBCc was higher among patients previously medicated. After treatment with risperidone, olanzapine, quetiapine, perphenazine, and haloperidol, TWBCc decreased significantly (p < 0.05). Lower baseline TWBCc predicted greater reductions in Positive and Negative Syndrome Scale (PANSS) total and negative scores over time (p < 0.05). We found significant mediation of TWBCc for effects of waist circumference, fasting low-density lipoprotein cholesterol, and glucose on reductions in PANSS total scores and PANSS negative subscale scores (p < 0.05). Conclusion: TWBCc is affected by certain antipsychotics among patients with schizophrenia, with decreases observed following short-term, but increases following long-term treatment. TWBCc is predictive of drug response, with lower TWBCc predicting better responses to antipsychotics. It also mediates the effects of certain metabolic measures on improvement of negative symptoms. This indicates that the metabolic state may affect clinical manifestations through inflammation.

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.

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.

Abstract Background Psychotic symptoms are prevalent in patients with bipolar disorder (BD). However, nearly all previous studies on differences in sociodemographic and clinical factors between patients with (BD P +) and without (BD P-) psychotic symptoms were conducted in Western populations, and limited information is known in China. Method A total of 555 patients with BD from seven centers across China were recruited. A standardized procedure was used to collect patients’ sociodemographic and clinical characteristics. The patients were divided into BD P + or BD P- groups based on the presence of lifetime psychotic symptoms. Mann–Whitney U test or chi-square test was used to analyze differences in sociodemographic and clinical factors between patients with BD P + and BD P-. Multiple logistic regression analysis was conducted to explore factors that were independently correlated with psychotic symptoms in BD. All the above analyses were re-conducted after the patients were divided into BD I and BD II group according to their types of diagnosis. Results A total of 35 patients refused to participate, and the remaining 520 patients were included in the analyses. Compared with patients with BD P-, those with BD P + were more likely to be diagnosed with BD I and mania/hypomania/mixed polarity in the first mood episode. Moreover, they were more likely to be misdiagnosed as schizophrenia than major depressive disorder, were hospitalized more often, used antidepressants less frequently, and used more antipsychotics and mood stabilizers. Multivariate analyses revealed that diagnosis of BD I, more frequent misdiagnosis as schizophrenia and other mental disorders, less frequent misdiagnosis as major depressive disorder, more frequent lifetime suicidal behavior, more frequent hospitalizations, less frequent use of antidepressants, more frequent use of antipsychotics and mood stabilizers were independently correlated with psychotic symptoms in BD. After dividing the patients into BD I and BD II groups, we observed notable differences in sociodemographic and clinical factors, as well as clinicodemographic correlates of psychotic features between the two groups. Conclusions Differences in clinical factors between patients with BD P + and BD P- showed cross-cultural consistency, but results on the clinicodemographic correlates of psychotic features were not. Notable differences between patients with BD I and BD II were found. Future work exploring the psychotic features of BD needs to take types of diagnosis and cultural differences into consideration. Trial registration This study was first registered on the website of the ClinicalTrials.gov ( https://clinicaltrials.gov/ ) on 18/01/2013. Its registration number is NCT01770704.

Background: Since the early clinical efficacy of antipsychotics has not yet been well perceived, this study sought to decide whether the efficacy of antipsychotics at week 2 can predict subsequent responses at week 6 and identify how such predictive capacities vary among different antipsychoticsand psychotic symptoms. Methods: A total of 3010 patients with schizophrenia enrolled in a randomized controlled trial (RCT) and received a 6-week treatment with one antipsychotic drug randomly chosen from five atypical antipsychotics (risperidone 2-6 mg/d, olanzapine 5-20 mg/d, quetiapine 400-750 mg/d, aripiprazole 10-30 mg/d, and ziprasidone 80-160 mg/d) and two typical antipsychotics (perphenazine 20-60 mg/d and haloperidol 6-20 mg/d). Early efficacy was defined as the reduction rate using the Positive and Negative Syndrome Scale (PANSS) total score at week 2. With cut-offs at 50% reduction, logistic regression, receiver operating characteristic (ROC) and random forests were adopted. Results: The reduction rate of PANSS total score and improvement of psychotic symptoms at week 2 enabled subsequent responses to 7 antipsychotics to be predicted, in which improvements in delusions, lack of judgment and insight, unusual thought content, and suspiciousness/ persecution were endowed with the greatest weight. Conclusion: It is robust enough to clinically predict treatment responses to antipsychotics at week 6 using the reduction rate of PANSS total score and symptom relief at week 2. Psychiatric clinicians had better determine whether to switch the treatment plan by the first 2 weeks.

AimAppraise the clinical features and influencing factors of the hospitalization times and length of stay in bipolar disorder (BD) patients.MethodsThis is a multicenter, observational, cohort study of patients diagnosed of type I or type II bipolar disorder. Five hundred twenty outpatients in seven hospitals from six cities in China were recruited from February 2013 to June 2014 and followed up using a continuous sampling pattern. The research included a retrospective period of 12 months and the prospective period of 9 months. The demographic and clinical features of the patients were collected. The influencing factors that could affect the length of stay (number of days spent in the hospital in the prospective period) were analyzed by poisson's regression and the hospitalization times (times of hospitalization in the prospective and retrospective period) was analyzed by general linear model. The selected variables included gender, age, years of education, occupational status, residence status, family history of mental disease, comorbid substance abuse, comorbid anxiety disorder, times of suicide (total suicide times that occurred in the retrospective and prospective period), polarity of the first mood episode, and BD type(I/II).ResultsPoisson's regression analysis showed that suicide times [Incidence Rate Ratio (IRR) = 1.20, p < 0.001], use of antipsychotic (IRR = 0.62, p = 0.011), and use of antidepressant (IRR = 0.56, p < 0.001) were correlated to more hospitalization times. Linear regression analysis showed that BD type II (β = 0.28, p = 0.005) and unemployment (β = 0.16, p = 0.039) which might mean longer duration of depression and poor function were correlated to longer length of stay. However, patients who experienced more suicide times (β = −0.21, p = 0.007) tended to have a shorter length of stay.ConclusionOverall, better management of the depressive episode and functional rehabilitation may help to reduce the length of stay. BD patients with more hospitalization times were characterized by higher risk of suicide and complex polypharmacy. Patients at high risk of suicide tended to have inadequate therapy and poor compliance, which should be assessed and treated adequately during hospitalization.Clinical trial registrationwww.ClinicalTrials.gov, Identifier: NCT01770704.

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.

Kai-Xin-San (KXS) is a Chinese medicine formulation that is commonly used to treat depression caused by dual deficiencies in the heart and spleen. Recent studies indicated that miRNAs were involved in the pathophysiology of depression. However, there have been few studies on the mechanism underlying the miRNAs directly mediating antidepressant at clinical level, especially in nature drugs and TCM compound. In this study, we identified circulating miRNAs defferentially expressed among the depression patients (DPs), DPs who underwent 8weeks of KXS treatment and health controls (HCs). A total of 45 miRNAs (17 were up-regulated and 28 were down-regulated) were significantly differentially expressed among three groups. Subsequently, qRT-PCR was used to verify 10 differentially expressed candidate miRNAs in more serum samples, and the results showed that 6 miRNAs (miR-1281, miR-365a-3p, miR-2861, miR-16-5p, miR-1202 and miR-451a) were consistent with the results of microarray. Among them, miR-1281, was the novel dynamically altered and appeared to be specifically related to depression and antidepressant effects of KXS. MicroRNA-gene-pathway-net analysis showed that miR-1281-regulated genes are mostly key nodes in the classical signaling pathway related to depression. Additionally, our data suggest that ADCY1 and DVL1 were the targets of miR-1281. Thus, based on the discovery of miRNA expression profiles in vivo, our findings suggest a new role for miR-1281 related to depression and demonstrated in vitro that KXS may activate cAMP/PKA/ERK/CREB and Wnt/β-catenin signal transduction pathways by down-regulating miR-1281 that targets ADCY1 and DVL1 to achieve its role in neuronal cell protection.

目的 观察青年和老年小鼠吸入异氟醚后对学习记忆、海马线粒体、突触以及神经元树突形态的影响.方法 青年(6月龄)及老年(18月龄)雄性C57BL/6小鼠各20只,随机分为4组(n=10):青年组、青年吸醚组、老年组和老年吸醚组.青年组和老年组均吸入1 000 mL/L O2 2 h,青年吸醚组和老年吸醚组均吸入15 mL/L异氟醚气体2h;通过新奇物体识别测试观察小鼠的行为表现,评估其学习记忆能力;使用透射电镜技术观察小鼠海马线粒体和突触的区域分布及超微结构;利用高尔基染色观察海马神经元树突形态变化.结果 ①与青年组相比,老年组对新物体的探索率降低(P＜0.05),树突棘数量减少(P＜0.01),线粒体面积增大(P＜0.05),线粒体密度降低(P＜0.01),突触数量减少且结构模糊.②与青年组相比,青年吸醚组对新物体的探索率减少(P＜0.05),树突长度变短(P＜0.05),树突分支数量减少(P＜0.01),线粒体面积增大(P＜0.01),突触结构被破坏;与老年组相比,老年吸醚组的新物体探索率降低(P＜0.01),树突长度、分支和树突棘数量均发生显著性下调(均P＜0.05),线粒体面积增大、密度降低(P＜0.05),突触结构受损严重.③与青年吸醚组相比,老年吸醚组的新物体探索率降低(P＜0.01),树突长度减小(P＜0.05),树突棘减少(P＜0.01),线粒体面积增大(P＜0.05),密度降低(P＜0.01),突触小泡受损严重,突触数量较少.结论 异氟醚会造成小鼠学习记忆功能下降,表现为海马神经元树突形态改变、线粒体和突触受损,并且这种损伤对老年小鼠更为严重.

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.

Abstract Background Lamotrigine is approved as a maintenance therapy for bipolar I disorder in many countries, including China in 2021. This study evaluated the efficacy and safety of lamotrigine in controlling relapse and/or recurrence of mood episodes in Chinese patients with bipolar I disorder. Methods Patients aged ≥ 18 years with bipolar I disorder who met response criteria (Clinical Global Impression–Severity [CGI-S] score of ≤ 3 for ≥ 4 consecutive weeks) during treatment with lamotrigine in a 6–16 week open-label (OL) phase, and who were maintained for ≥ 1 week on lamotrigine 200 mg/day monotherapy, were randomised (1:1) to continue receiving lamotrigine 200 mg/day or switch to placebo in a 36-week randomised double-blind (RD) phase. The primary efficacy outcome measure was time from entry into the RD phase to intervention for relapse and/or recurrence of a mood episode (TIME). Post hoc analyses assessed the impact of OL baseline mood severity on TIME. Safety assessments were conducted throughout the study. Results Of 420 patients treated in the OL phase, 264 were randomised to receive lamotrigine (n = 131) or placebo (n = 133). Overall, 112 patients had an intervention for relapse and/or recurrence of a mood episode (lamotrigine, n = 50/130 [38.5%]; placebo, n = 62/133 [46.6%]), with no significant difference in TIME between groups (adjusted hazard ratio [95% confidence interval (CI)] 0.93 [0.64, 1.35]; p = 0.701). Post hoc analyses indicated a significant difference in TIME, favouring lamotrigine over placebo, for patients with baseline CGI-S score ≥ 4 (hazard ratio [95% CI] 0.52 [0.30, 0.89]; p = 0.018) and with baseline Hamilton Depression Rating Scale ≥ 18 or Young Mania Rating Scale ≥ 10 (0.44 [hazard ratio [95% CI] 0.25, 0.78]; p = 0.005). Lamotrigine was well tolerated with no new safety signals. Conclusions Lamotrigine was not significantly superior to placebo in preventing relapse and/or recurrence of mood episodes in this study of Chinese patients with bipolar I disorder but post hoc analyses suggested a therapeutic benefit in patients with moderate/severe mood symptoms at baseline. The discrepancy between these findings and the positive findings of the pivotal studies may be attributable to the symptom severity of the bipolar patients recruited, a high dropout rate, and the comparatively short duration of the RD phase rather than race/ethnicity differences. Clinical trial registration ClinicalTrial.gov Identifier NCT01602510; 21st May 2012; https://clinicaltrials.gov/ct2/show/NCT01602510 .

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.

Background and Objectives: Lipidomics is a pivotal tool for investigating the pathogenesis of mental disorders. However, studies qualitatively and quantitatively analyzing peripheral lipids in adult patients with schizophrenia (SCZ) and major depressive disorder (MDD) are limited. Moreover, there are no studies comparing the lipid profiles in these patient populations. Materials and Method: Lipidomic data for plasma samples from sex- and age-matched patients with SCZ or MDD and healthy controls (HC) were obtained and analyzed by liquid chromatography-mass spectrometry (LC-MS). Results: We observed changes in lipid composition in patients with MDD and SCZ, with more significant alterations in those with SCZ. In addition, a potential diagnostic panel comprising 103 lipid species and another diagnostic panel comprising 111 lipid species could distinguish SCZ from HC (AUC = 0.953) or SCZ from MDD (AUC = 0.920) were identified, respectively. Conclusions: This study provides an increased understanding of dysfunctional lipid composition in the plasma of adult patients with SCZ or MDD, which may lay the foundation for identifying novel clinical diagnostic methods for these disorders.

ObjectiveRepetitive transcranial magnetic stimulation (rTMS) can effectively improve depression symptoms in patients with major depressive disorder (MDD); however, its mechanism of action remains obscure. This study explored the neuralimaging mechanisms of rTMS in improving depression symptoms in patients with MDD.MethodsIn this study, MDD patients with first-episode, drug-naive (n = 29) and healthy controls (n = 33) were enrolled. Depression symptoms before and after rTMS treatment were assessed using the Hamilton Depression Rating Scale (HAMD-17). Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected both before and after the treatment. Changes in the brain function after the treatment were compared using the following two indices: the amplitude of the low-frequency fluctuation (ALFF) and regional homogeneity (ReHo), which are sensitive for evaluating spontaneous neuronal activity. The brain region with synchronous changes was selected as the seed point, and the differences in the causal connectivity between the seed point and whole brain before and after rTMS treatment were investigated via Granger causality analysis (GCA).ResultsBefore treatment, patients with MDD had significantly lower ALFF in the left superior frontal gyrus (p < 0.01), higher ALFF in the left middle frontal gyrus and left precuneus (p < 0.01), and lower ReHo in the left middle frontal and left middle occipital gyri (p < 0.01) than the values observed in healthy controls. After the rTMS treatment, the ALFF was significantly increased in the left superior frontal gyrus (p < 0.01) and decreased in the left middle frontal gyrus and left precuneus (p < 0.01). Furthermore, ReHo was significantly increased in the left middle frontal and left middle occipital gyri (p < 0.01) in patients with MDD. Before treatment, GCA using the left middle frontal gyrus (the brain region with synchronous changes) as the seed point revealed a weak bidirectional causal connectivity between the middle and superior frontal gyri as well as a weak causal connectivity from the inferior temporal to the middle frontal gyri. After treatment, these causal connectivities were strengthened. Moreover, the causal connectivity from the inferior temporal gyrus to the middle frontal gyri negatively correlated with the total HAMD-17 score (r = −0.443, p = 0.021).ConclusionrTMS treatment not only improves the local neural activity in the middle frontal gyrus, superior frontal gyrus, and precuneus but also strengthens the bidirectional causal connectivity between the middle and superior frontal gyri and the causal connectivity from the inferior temporal to the middle frontal gyri. Changes in these neuroimaging indices may represent the neural mechanisms underlying rTMS treatment in MDD.Clinical Trial RegistrationThis study was registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR1800019761).

Objective:This study explored the impacts of repetitive transcranial magnetic stimulation (rTMS) on spontaneous brain activity in patients with major depressive disorder (MDD).Methods:This study was a randomized controlled study. First-episode, drug-na?ve patients with MDD ( n=27) and healthy controls ( n=30) were enrolled. The left dorsolateral prefrontal region was the stimulation target, and all participants received rTMS treatment for fifteen successive days. Hamilton Depression Rating Scale (HAMD 17) and resting-state functional magnetic resonance imaging (rs-fMRI) data were collected at baseline and the 15th day of the treatment. Changes in the spontaneous brain activity before and after the treatment were compared using the paired samples t-test or the independent sample t-test. The two indices of the amplitude of the low-frequency fluctuation (ALFF) and regional homogeneity(ReHo) were applied to reflect the spontaneous brain activity. Results:After treatment, the score of HAMD 17 (9.4±4.3) in MDD patients was significantly lower than that before the treatment (21.1±6.0), the average score decreased by (11.7±3.6), the remission rate was 40.74%, and the response rate was 74.07%. fMRI results: Before treatment, patients with MDD had significantly lower ALFF in the left superior frontal gyrus ( t=-8.14, P<0.001), higher ALFF in the left middle frontal gyrus and left precuneus ( t=5.79, 6.24, P<0.001), and lower ReHo in the left middle frontal and left middle occipital gyri ( t=-5.17, -6.11, P<0.001) than the corresponding values observed in healthy controls; After the rTMS treatment, the ALFF significantly increased in the left superior frontal gyrus ( t=7.32, P<0.001) and decreased in the left middle frontal gyrus and left precuneus ( t=-4.96,-5.14, P<0.001). Furthermore, ReHo significantly increased in the left middle frontal and left middle occipital gyri ( t=4.25,4.19, P<0.001) in patients with MDD. The score of HAMD 17 after treatment was significantly and negatively correlated with ALFF value of left superior frontal gyrus after treatment ( r=-0.390, P=0.044). Conclusion:Successive 15-day rTMS treatment could efficiently and effectively alleviate individual′s depressive symptoms. The left middle frontal gyrus may play an important role in abnormal spontaneous brain activity in MDD patients; and left superior frontal gyrus function may be essential in improving depressive symptoms.

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.

目的 观察重复经颅磁刺激(rTMS)对慢性不可预见应激(CUS)模型大鼠海马鞘磷脂(SM)和神经酰胺(Cer)水平的影响.方法 将24只SD大鼠随机分为对照组(Sham组)、模型组(CUS组)和rTMS干预组(CUS+rTMS组),每组8只.CUS组和CUS+rTMS组大鼠均接受CUS造模(28 d),造模结束后,CUS+rTMS组每日接受rTMS(5 Hz,1.26 Tesla)干预;Sham组和CUS组在每日同一时间段接受假rTMS干预,连续7 d.通过糖水偏好实验和强迫游泳实验检测各组大鼠的抑郁样行为,在行为学检测结束后,处死大鼠,分离海马组织,通过高效液相色谱-质谱联用技术检测海马SM和Cer水平及组成小分子差异.采用SPSS 19.0软件分析各组大鼠海马中SM和Cer相对含量与行为学的相关性.结果 ①CUS模型可诱导大鼠抑郁样行为,显著降低海马SM水平但显著提高Cer相对丰度;rTMS干预能够改善CUS所致大鼠的抑郁样行为,并部分改善CUS大鼠海马SM和Cer水平的变化.②与Sham组相比,CUS组7个SM和1个Cer小分子相对丰度降低,13个Cer小分子相对丰度升高(P＜0.05,P＜0.01);③与CUS组相比,CUS+rTMS组3个SM和1个Cer小分子相对丰度升高,11个Cer小分子相对丰度降低(P＜0.01);与Sham组相比,CUS+rTMS组2个Cer小分子相对丰度降低,1个SM和1个Cer小分子相对丰度升高(P＜0.05,P＜0.01);④各组海马中的SM相对含量与强迫游泳不动时间呈负相关,与糖水偏好率呈显著正相关(P＜0.05);Cer相对含量与强迫游泳不动时间呈显著正相关(P＜0.01),与糖水偏好率呈显著负相关性(P＜0.01).结论 通过调节大鼠海马中SM和Cer相对含量和组成变化,rTMS可以改善CUS模型大鼠抑郁样行为,并且SM和Cer相对含量与抑郁样行为密切相关.

BACKGROUND:Ansofaxine (LY03005) extended-release tablet is a potential triple reuptake inhibitor of serotonin, norepinephrine, and dopamine. This study assessed the efficacy, safety, and appropriate dosage of ansofaxine for the treatment of major depressive disorder (MDD). METHODS:A multicenter, randomized, double-blind, placebo-controlled, dose-finding, Phase 2 clinical trial was conducted in China. Eligible patients with MDD (18-65 years) were randomly assigned to receive fixed-dose ansofaxine extended-release tablets (40, 80, 120, or 160 mg/d) or placebo for 6 weeks. The primary outcome measure was a change in the total score on the 17-item Hamilton Depression Rating Scale from baseline to week 6. RESULTS:A total of 260 patients were recruited from October 2015 to September 2017, and 255 patients received the study drug as follows: 40 mg (n = 52), 80 mg (n = 52), 120 mg (n = 51), and 160 mg (n = 51) ansofaxine and placebo (n = 49). Significant differences were found in mean changes in 17-item Hamilton Depression Rating Scale total scores at week 6 in the 4 ansofaxine groups vs placebo (-12.46; χ2 = -9.71, P = .0447). All doses of ansofaxine were generally well-tolerated. Treatment-related adverse events occurred in 141 patients (303 cases), yielding incidence rates of 51.92%, 65.38%, 56.86%, and 62.75% in the 40-, 80-, 120-, and 160-mg ansofaxine groups and 38.78% in the placebo group. CONCLUSION:Active doses (40, 80, 120, and 160 mg/d) of ansofaxine in a controlled setting were safe, tolerated, and effective in improving depression symptoms in MDD patients.