Population Pharmacodynamic Models of Risperidone on PANSS Total Scores and Prolactin Levels in Schizophrenia.

Currently, research predominantly focuses on evaluating clinical effects at specific time points while neglecting underlying patterns within the treatment process. This study aims to analyze the dynamic alterations in PANSS total scores and prolactin levels in patients with schizophrenia treated with risperidone, along with the influencing covariates. Using data from an 8-week randomized, double-blind, multicenter clinical trial, a population pharmacodynamic model was established for the PANSS total scores of and prolactin levels in patients treated with risperidone. The base model employed was the Emax model. Covariate selection was conducted using a stepwise forward inclusion and backward elimination approach. A total of 144 patients were included in this analysis, with 807 PANSS total scores and 531 prolactin concentration values. The PANSS total scores of the patients treated with risperidone decreased over time, fitting a proportionally parameterized sigmoid Emax model with covariates including baseline score, course of the disease, gender, plasma calcium ions, and lactate dehydrogenase levels. The increase in prolactin levels conformed to the ordinary Emax model, with covariates encompassing course of the disease, gender, weight, red blood cell count, and triglyceride levels. The impacts of the baseline scores and the course of the disease on the reduction of the PANSS scores, as well as the influence of gender on the elevation of prolactin levels, each exceeded 20%. This study provides valuable quantitative data regarding PANSS total scores and prolactin levels among patients undergoing risperidone treatment across various physiological conditions.

Safety, tolerability, and pharmacokinetics of JX11502MA in Chinese healthy subjects: a first-in-human, randomized, double-blind, placebo-controlled study following single-dose administration.

BACKGROUND: JX11502MA is a potent partial agonist of dopamine D2 and D3 receptors, with a preferential binding profile for D3 receptors in vitro, potentially for treating schizophrenia. METHODS: A first-in-human, randomized, double-blind, placebo-controlled, single ascending dose clinical trial was designed. The subjects were randomly assigned to receive JX11502MA and placebo capsules with seven ascending dose groups: 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 6 mg, and 8 mg. The PK profiles of JX11502MA and its metabolites were evaluated, along with a safety and tolerability assessment. RESULTS: Considering the safety of participants, the dose escalation was halted at 3 mg. Following single-dose administration, JX11502MA exhibited rapid absorption with a median Tmax ranging from 1 to 1.75 h. The terminal half-life of JX11502MA ranged from 73.62 to 276.85 h. The most common treatment-emergent adverse events (TEAEs) for subjects receiving JX11502MA were somnolence (56.3%), dizziness (18.8%), nausea (21.9%), vomiting (18.8%), and hiccups (18.8%). CONCLUSIONS: JX11502MA was generally well tolerated at a single dose of 0.25 to 3 mg. The PK profiles and safety characteristics in this study indicated that JX11502MA has the potential to be a favorable treatment option for patients with schizophrenia. TRIAL REGISTRATION: https://clinicaltrials.gov (identifier: NCT05233657).

A 6-week, phase IIb, randomized, double-blind, placebo-controlled trial of Anyu Peibo capsules for the treatment of major depressive disorder in adults.

Background: Almost one-third of patients with major depressive disorder (MDD) do not respond to conventional antidepressants, and new treatments for MDD are urgently needed. Objectives: This phase IIb clinical trial was designed to evaluate the efficacy and safety of Anyu Peibo capsules in the treatment of adults with MDD. Design: A multicenter, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose study. Methods: A total of 172 patients with MDD from nine study centers were randomized (1:1) to receive placebo (n = 86) or oral Anyu Peibo capsules (0.8 g) twice per day (n = 86) for 6 weeks. The primary endpoint was the change in the Montgomery Åsberg Depression Rating Scale (MADRS) total score from baseline to week 6, analyzed using an analysis of covariance (ANCOVA) approach with the baseline MADRS score, center effect and center by group interaction as the covariates. Other efficacy endpoints and variables included clinical response and remission rates according to the MADRS and the 17-item Hamilton Depression Rating Scale (HAMD-17) scores, the change in the HAMD-17, Clinical Global Impression - Severity scale and Clinical Global Impression - Improvement scale scores and the reduction in the Hamilton Anxiety Scale from baseline to week 6. Results: The mean baseline MADRS total scores were 29.20 and 29.72 in the Anyu Peibo (n = 82) and placebo groups (n = 81), respectively. The least squares mean change in the MADRS score from baseline to week 6 was 16.59 points in the Anyu Peibo group and 14.51 points in the placebo group. Although there were greater reductions in the MADRS score from baseline to week 6 in the Anyu Peibo capsule group compared to the placebo group, the difference did not reach statistical significance (least-squares mean difference, 2.07 points; 95% confidence interval, -0.27 to 4.41; p = 0.0819). The results of sensitivity analyses by ANCOVA with the last observation carried forward method for missing data indicated that the administration of Anyu Peibo capsules may lead to a significant reduction in depressive symptoms compared to the placebo (least-squares mean difference: 3.29 points; 95% confidence interval: 0.64-5.93; p = 0.0152). Furthermore, Anyu Peibo capsules showed significant benefits over placebo when the change in the HAMD-17 score from baseline to week 6 was evaluated as the secondary analysis (t = 2.01; 95% confidence interval, 0.03-4.23; p = 0.0464). Conclusion: Anyu Peibo capsules may have an effective and safe antidepressant effect, which warrants further research.

Prediction of anticancer peptides based on an ensemble model of deep learning and machine learning using ordinal positional encoding.

Anticancer peptides (ACPs) are the types of peptides that have been demonstrated to have anticancer activities. Using ACPs to prevent cancer could be a viable alternative to conventional cancer treatments because they are safer and display higher selectivity. Due to ACP identification being highly lab-limited, expensive and lengthy, a computational method is proposed to predict ACPs from sequence information in this study. The process includes the input of the peptide sequences, feature extraction in terms of ordinal encoding with positional information and handcrafted features, and finally feature selection. The whole model comprises of two modules, including deep learning and machine learning algorithms. The deep learning module contained two channels: bidirectional long short-term memory (BiLSTM) and convolutional neural network (CNN). Light Gradient Boosting Machine (LightGBM) was used in the machine learning module. Finally, this study voted the three models' classification results for the three paths resulting in the model ensemble layer. This study provides insights into ACP prediction utilizing a novel method and presented a promising performance. It used a benchmark dataset for further exploration and improvement compared with previous studies. Our final model has an accuracy of 0.7895, sensitivity of 0.8153 and specificity of 0.7676, and it was increased by at least 2% compared with the state-of-the-art studies in all metrics. Hence, this paper presents a novel method that can potentially predict ACPs more effectively and efficiently. The work and source codes are made available to the community of researchers and developers at https://github.com/khanhlee/acp-ope/.

Long-Term Antipsychotic Effectiveness and Comparison of the Efficacy of Monotherapy and Polypharmacy in Schizophrenia: A 3-Years Follow-Up "Real World" Study in China.

Background: Discontinuation of antipsychotic treatment is a common problem in patients with schizophrenia and could reduce the effectiveness of treatment. Time to discontinuation (TTD) is one of the indicators of compliance and may also be an effective indicator of medication efficacy. The aim of the study was to compare the clinical effectiveness of quetiapine, olanzapine, risperidone, and aripiprazole in the real-world treatment of schizophrenia with 3-years follow-up. Method: A multi-center, open, cohort, prospective, real-world study was conducted. 706 patients were analyzed without intervention in medication selection and use, followed up for 3 years. Kaplan-Meier survival curves were used to draw the treatment discontinuation rates (TDR) curves at each time point. Cox proportional hazard regression model was used to assess the relative risk of TTD of antipsychotics. Results: There was a significant difference among monotherapy groups in all-cause antipsychotic treatment discontinuation (p = 0.0057). Among the four medications, the TDR of risperidone was the highest. Compared with polypharmacy, except for aripiprazole, the TDR of other three monotherapy medications were lower than that of polypharmacy, and olanzapine was statistically different (p = 0.0325). The cox regression analysis showed that after correction of Hochberg with multiple tests, only olanzapine had a relative risk lower than risperidone (p < 0.0083). Conclusions: The findings indicated that risperidone monotherapy and polypharmacy had the highest TDR and the shortest TTD. Olanzapine monotherapy had a relative risk lower than risperidone and was superior to polypharmacy.

Association between Tumor Necrosis factor-Alpha(TNF-a) polymorphisms and Schizophrenia: an updated meta-analysis.

BACKGROUND: Previous studies have explored associations between Tumour Necrosis factor-Alpha (TNF-a) polymorphisms and Schizophrenia. Their results were controversial. We conducted a meta-analysis to clarify the association between TNF-a - 308 G/A(rs1800629), -1031T/C(rs1799964), -863C/A(rs1800630) and -857 C/T (rs1799724) polymorphisms and Schizophrenia. METHODS: All the studies that investigated the association between TNF-a polymorphisms and Schizophrenia published before 15 October 2020 were included in. The literature were comprehensively searched and identified in 2 English databases and 2 Chinese databases. The odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: For -1031 T/C polymorphism, at the overall analysis, significantly decreased Schizophrenia risk was found in T allele in the allele model (p = 0.006, OR = 0.88) and increased Schizophrenia risk was found in TC + CC genotype in the dominant model (p = 0.005, OR = 1.17). Similarly, the same results were obtained when pooled analyses were included in high-quality studies (allele model: p = 0.005, OR = 0.86; dominant model: p = 0.007, OR = 1.20). In addition, when stratified by ethnicity, the results showed that in allele model, the T allele decreased Schizophrenia risk in East Asian (p = 0.031, OR = 0.90). CONCLUSION: The association may most likely result from less-credible, rather than from true associations or biological factors on the TNF-a - 1031 T/C polymorphism with Schizophrenia risk.KeypointsFor -1031T/C polymorphism, at the overall analysis, significantly decreased schizophrenia risk was found in T allele in the allele model, and increased schizophrenia risk was found in TC + CC genotype in the dominant model.In allele model, the T allele decreased schizophrenia risk in East Asian when stratified by ethnicity, and in the dominant model, TC + CC genotype increased schizophrenia risk in East Asian.

A Real-World Study of Risk Factors for QTc Prolongation in Schizophrenia Patients Receiving Atypical Antipsychotics.

PURPOSE: The risk of sudden cardiac death in patients receiving atypical antipsychotics may be related to QTc prolongation. The aim of this study was to investigate the risk factors for QTc prolongation to prevent QTc prolongation and guide clinical practice. METHODS: All electrocardiogram recordings of 913 schizophrenia patients who were receiving atypical antipsychotics were reviewed for prolonged QTc and associated conditions. Binary logistic regression analysis was used to investigate risk factors for QTc prolongation. RESULTS: Logistic regression analysis demonstrated that sex (odds ratio [OR], 0.386; P = 0.010), age (OR, 1.047; P = 0.000), high-density lipoprotein (OR, 0.257; P = 0.014), and antipsychotics dose (OR, 1.040; P = 0.036) were significantly associated with QTc prolongation. CONCLUSIONS: In patients with male sex, elder age, low high-density lipoprotein, or large antipsychotics dose, QTc should be monitored more frequently.

An Intelligent Control Model of Credit Line Computing in Intelligence Health-Care Systems.

Technologies such as machine learning and artificial intelligence have brought about a tremendous change to biomedical computing and intelligence health care. As a principal component of the intelligence healthcare system, the hospital information system (HIS) has provided great convenience to hospitals and patients, but incidents of leaking private information of patients through HIS occasionally occur at times. Therefore, it is necessary to properly control excessive access behavior. To reduce the risk of patient privacy leakage when medical data are accessed, this article proposes a dynamic permission intelligent access control model that introduces credit line calculation. According to the target given by the doctor in HIS and the actual access record, the International Classification of Diseases (ICD)-10 code is used to describe the degree of correlation, and the rationality of the access is formally described by a mathematical formula. The concept of intelligence healthcare credit lines is redefined with relevance and time Windows. The access control policy matches the corresponding credit limit and credit interval according to the authorization rules to achieve the purpose of intelligent control. Finally, with the actual data provided by a Grade-III Level-A hospital in Kunming, the program code is written through machine learning and biomedical computing-related technologies to complete the experimental test. The experiment proves that the intelligent access control model based on credit computing proposed in this study can play a role in protecting the privacy of patients to a certain extent.

The efficacy and safety of Anyu Peibo Capsule in the treatment of patients with major depressive disorder in China: study protocol for a randomized placebo-controlled trial.

BACKGROUND: Major depressive disorder is the second leading cause of years lost to disability worldwide. Anyu Peibo Capsule has been shown to be effective and safe in phase II trials. METHODS: This clinical study is a multi-center, randomized, double-blinded, placebo-controlled, parallel-group, phase III trial of Anyu Peibo Capsule in China. The aim is to test whether the administration of Anyu Peibo Capsule compared to placebo improves clinical outcomes in adults (aged 18 to 65 years) with MDD. Patients will receive an 8-week treatment of Anyu Peibo Capsule 1.6 g per day or placebo. The primary outcome will be the change from baseline in the total score for the Montgomery-Asberg Depression Rating Scale at the end of the 8-week treatment. DISCUSSION: The trial aims to provide pivotal evidence for the efficacy and safety of Anyu Peibo Capsule in patients with major depressive disorder. TRIAL REGISTRATION: ClinicalTrials.gov NCT04210973 . Registered on December 26, 2019.

Preparation and characterization of kafirin-quercetin film for packaging cod during cold storage.

This study mainly evaluated the physical properties of kafirin-quercetin (KQ) edible films and their application on the quality of cod fillets during cold storage. The results showed that the addition of quercetin significantly increased mechanical properties of KQ films, while decreased water vapor permeability, water solubility, and transparency. As quercetin was 0.4% (wt/vol), the film had the highest tensile strength (4.96 ± 1.23 MPa), the lowest water vapor permeability (1.08 ± 0.09 g·mm·m-2 ·h·KPa-1 ) and water solubility (22.02 ± 0.45%). Moreover, compared with the pure kafirin and polythylene films, KQ films could effectively inhibit the cod meat deterioration by restraining the growth of microorganisms and decreasing TVB-N and TBARs. The KQ0.4% film was the best to prolong the shelf life of cod fillets during cold storage. Therefore, KQ edible films could be used as a potential food packaging material to protect and retain the quality of aquatic products.

Promoter Hypomethylation of miR-124 Gene Is Associated With Major Depressive Disorder.

Based on our previous studies and other evidence, miR-124 is an important biomarker and therapeutic target for major depressive disorder (MDD). The aim of this study was to clarify the role of miR-124 methylation in MDD and antidepressant effects from the perspective of epigenetics. MethylTarget™ was used to detect methylation levels of the three miR-124 precursor genes (MIR124-1, MIR124-2, and MIR124-3) in 33 pre- and post-treatment MDD patients and 33 healthy controls. A total of 11 cytosine-phosphate-guanine (CpG) islands in the three miR-124 precursor genes, including 222 CpG sites, were detected. All CpG islands were hypomethylated in MDD patients when compared to healthy controls and seven CpG regions were still identified with a statistically significant difference after Bonferroni correction. In addition, 137 of 222 CpG sites were found a statistical difference between MDD patients and controls, and 40 CpG sites were still statistically significant after Bonferroni correction. After performing the LASSO regression model, seven biomarkers with differential methylation among 40 CpG sites were identified. Mean methylation score was lower in MDD patients (z = -5.84, p = 5.16E-9). The AUC value reached 0.917 (95% CI: 0.854-0.981) to discriminate MDD and controls. No changes in methylation of the three miR-124 precursor genes were found in MDD patients following antidepressant treatment. The methylation of miR-124 could be a promising diagnostic biomarker for MDD.

Characteristics and Spectrum of Cardiotoxicity Induced by Various Antipsychotics: A Real-World Study From 2015 to 2020 Based on FAERS.

Objective: This study aimed to investigate the characteristics and spectrum of cardiotoxicity induced by various antipsychotics based on the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. Methods: Data of the FAERS database from the first quarter of 2015 to the fourth quarter of 2020 were downloaded for disproportionality analysis. The significant signal was evaluated by reporting odds ratios and information components with statistical shrinkage transformation. Results: A total of 2,361,487 records were extracted for disproportionality analysis. Among the 10 antipsychotics, clozapine and amisulpride performed strong cardiotoxicity. Cardiomyopathy, cardiac arrhythmia, and Torsade de pointes/QT prolongation were the common cardiac adverse event induced by antipsychotics. Different characteristics of the spectrum of cardiotoxicity in various APs were discovered after further data mining. Moreover, evidence of the association between antipsychotics and eosinophilic myocarditis, peripartum cardiomyopathy was provided in this study. Conclusion: Antipsychotics presented cardiotoxicity in different degrees, and more cardiac examinations should be monitored in patients with antipsychotics.

Network-based approach to identify molecular signatures in the brains of depressed suicides.

BACKGROUND: Suicide is a serious and global health problem that has a strong association with major depressive disorder (MDD). Weighted gene co-expression network analysis (WGCNA) was performed for the construction of a co-expression network to get important gene modules associated with depressed suicide. METHODS: Transcriptome sequencing data from dorsolateral prefrontal cortex was used, which included 29 non-psychiatric controls (CON), 21 MDD suicides (MDD-S) and 9 MDD non-suicides (MDD-NS) of medication-free sudden death individuals. RESULTS: The highest correlation in the module-traits relationship was discovered between the black module and suicide (r = -0.30, p = 0.024) as well as MDD (r = -0.34, p = 0.010).Furthermore, the expression levels of genes decreased progressively across the three groups (CON>MDD-NS>MDD-S). Therefore, the genes in the black module was selected for subsequent analyses. Protein-Protein Interaction Network found that the top 10 hub genes were somehow involved in depressed suicide including JUN, FOS, ATF3, MYC, EGR1, FOSB, DUSP1, NFKBIA, TLR2, NR4A1. Most of the GO terms were enriched in cell death and apoptosis and KEGG was mainly enriched in MAPK pathway. Cell Type-Specific Analysis found these genes were significantly enriched in endothelial and microglia (p<0.000) cell types. In addition, 92 genes in this module had at least one highly significant differentially methylated positions between MDD-S and controls. CONCLUSION: Cell death and apoptosis may participate in the interplay between depressed suicide and neuro-inflammation system.

Effects of hourly levels of ambient air pollution on ambulance emergency call-outs in Shenzhen, China.

Some researches have shown the associations between air pollution and hospital-based emergency department visits, while the evidence about the acute effects of air pollution on emergency ambulance dispatches for the whole population is rarely available, especially on an hourly time scale. This paper aimed to investigate the effects of hourly concentrations of ambient air pollution on hourly number of ambulance emergency call-outs (AECOs) in Shenzhen, China. AECO data were collected from Shenzhen Emergency Center from January 2013 to December 2016. A time-stratified case-crossover design with conditional Poisson regression was performed to fit the relationship between hourly air pollution and AECOs. The distributed lag model was applied to determine lag structure of the effects of air pollutants. There were a total of 502,862 AECOs during the study period. The significant detrimental effects of SO2, PM2.5, and PM10 appeared immediately with a following harvesting effect after 5 h and the effects lasted for about 96 h. The cumulative effect estimates of four pollutants over 0-96 h were 13.99% (95% CI 7.52-20.85%), 2.07% (95% CI 0.72-3.43%), 1.20% (95% CI 0.54-1.87%), and 2.46% (95% CI 1.63-3.29%), respectively. We did not observe significant effects of O3. This population-based study quantifies the adverse effects of air pollution on ambulance dispatches and provides evidence of the lag structure of the effects on an hourly time scale.

Effects of hourly precipitation and temperature on road traffic casualties in Shenzhen, China (2010-2016): A time-stratified case-crossover study.

BACKGROUND: Although road traffic casualty (RTC) is preventable, it remains the eighth leading cause of death globally, especially in developing countries. Previous studies suggested the association between RTC and monthly or daily weather conditions, while the acute effects of weather conditions on an hourly timescale remains unknown. This study aims to quantify hourly effects of precipitation and temperature on RTC. METHODS: Using ambulance records on RTC during 2010-2016 for the whole population in Shenzhen, China, we conducted a time-stratified case-crossover design which can inherently control for hour of the day, day of the week, seasonality, time trends and potential time-invariant confounders. Conditional quasi-Poisson regression with distributed lag nonlinear model was used to determine the effects of hourly precipitation and temperature on RTC. RESULTS: Light and heavy precipitation increased RTC in current and following 2 h by 8.09% (95% CI: 4.20-12.12%) and 11.62% (95% CI: 5.93-17.62%), respectively. A J-shaped temperature-RTC curve revealed that each 1 °C increment above 17 °C were associated with a 0.87% (0.52-1.22%) increase in RTC. High temperature accounted for 6.44% (95% CI: 3.95-8.91%) of all RTC, with a high fraction of 10.64% (95% CI: 4.33-15.96%) during warm season and 8.30% (95% CI: 4.26-12.66%) in traffic peak hours. Precipitation contributed to 0.68% (95% CI: 0.44-0.92%) of RTC within 3 h. The middle-aged and female suffered more from precipitation-associated RTC, and the younger suffered more from high temperature-associated RTC. CONCLUSIONS: High temperature increased substantially hourly RTC. Precipitation was also a risk factor of RTC and the adverse effect lasted for 3 h. The findings would be helpful to guide the development of targeted intervention to accelerate progress in road traffic safety.

Model-based analysis of therapeutic efficacy of blonanserin and risperidone in schizophrenia patients and effects on prolactin: A randomized double-blind study.

This study examined randomized controlled trial data for blonanserin and risperidone in Chinese schizophrenia patients (N = 264). Data related to historical changes in the Positive and Negative Syndrome Scale (PANSS) were used to successfully construct a longitudinal Emax model. Results: (a) The efficacy of the two drugs was similar after week 8, showing a small difference in PANSS reduction. (b) Using the model, we predicted that each 5-point increase in the baseline FPOS (positive score in PANSS five-factor subscales) leads to a decrease in the PANSS total scores at week 8 for 2 points in patients administered blonanserin. (c) The effect of blonanserin on prolactin (PRL) elevation was less. The model was used to predict that prolactin elevations in patients administered risperidone were 2.41-fold of those in patients administered blonanserin. (d) Model quantitation showed that gender is a risk factor for prolactin elevation. Prolactin elevations in female patients were 2.95-fold of the value in male patients administered the same drug. The model demonstrated Blonanserin has similar antischizophrenic efficacy and less serum prolactin rising compared to risperidone in Chinese patients.

Effects of hourly precipitation and temperature on ambulance response time.

BACKGROUND: Longer ambulance response time (ART) delaying treatment would worsen conditions of seriously ill or injured patients, but limited evidence is available on the effects of weather factors on ART. This study aims to assess precipitation- and temperature-ART associations and their potential lagged effects using a novel modeling strategy. METHODS: Based on 779,156 emergency records during 2010-2016 from the whole population in Shenzhen, China, we creatively combined quantile regression with distributed-lag nonlinear models to examine the non-linear and lagged effects of hourly precipitation and temperature on ART at the 50th and 90th percentiles. RESULTS: A linear precipitation-ART association with a delay of 9.01 (95%CI, 7.82-10.20) seconds at median ART for a 1 mm increase in hourly precipitation, and the effects lasted for 5 h with the greatest effect at the current hour. A two linear thresholds temperature-ART association revealed 1 °C decrease below 19 °C caused 1.68 (95%CI, 0.92-2.44) seconds delay in total ART over lag 0-7 h, and 1 °C increase above 24 °C caused 2.44 (95%CI, 1.55-3.33) seconds delay. The hourly call volumes exceeding 54 calls caused 8.79 (95%CI, 8.71-8.86) seconds delay in total ART for 1 more call, but not affected the effects of weather factors. The internal ART suffered more from the hourly call volumes, while the external ART suffered more from precipitation and temperature. The effects were apparently greater on ART at the 90th percentile than median. CONCLUSIONS: Precipitation and temperature are independent risk factors for ambulance services performance, and their lagged effects are notable. The external ART and patients with long ART are vulnerable. More attention should be paid to weather and ART, and these findings may have implications for effective policies to reduce ART to protect public health.

Quantitative efficacy of three antipsychotic drugs for schizophrenia based on a real-world study in China.

Atypical antipsychotics exert remarkable long-term efficacy on the personal and social functions of schizophrenic patients. However, quantitative information on the social function of schizophrenic patients treated with atypical antipsychotics is scarce in the current clinical guidelines. In this study, we established pharmacodynamic models to quantify the time-efficacy relationship of three antipsychotic drugs based on the data from a real-world study conducted in China. A total of 373 schizophrenic patients who received antipsychotic monotherapy with olanzapine (n = 144), risperidone (n = 160), or aripiprazole (n = 69) were selected from a three-year prospective, multicenter study. The follow-up times were 13, 26, 52, 78, 104, 130, and 156 weeks after baseline. A time-efficacy model was developed with nonlinear mixed effect method based on changes in Personal and Social Performance (PSP) score compared with the baseline level. Crucial pharmacodynamic parameters, including maximum efficacy and drug onset time, were used to distinguish the efficacy of the three drugs. We quantified the time course of PSP improvement in patients after treatment with these three antipsychotics: olanzapine, risperidone, and aripiprazole reached an Emax value of 80.3%, 68.2%, and 23.9% at weeks 56.7, 29.2, and 36.8, respectively. General psychotic symptoms, onset frequency, and illness course were identified as significant factors affecting the efficacy of these drugs. The newly constructed models provide an evidence of the benefit of long-term maintenance therapy with atypical antipsychotics in individualized schizophrenia treatment in China.

Co-Expression Network Analysis Revealed That the ATP5G1 Gene Is Associated With Major Depressive Disorder.

Major depressive disorder (MDD) is a leading cause of disability worldwide, although its etiology and mechanism remain unknown. The aim of our study was to identify hub genes associated with MDD and to illustrate the underlying mechanisms. A weighted gene co-expression network analysis (WGCNA) was performed to identify significant gene modules and hub genes associated with MDD in peripheral blood mononuclear cells (PBMCs) (n = 45). In the blue module (R 2 = 0.95), five common hub genes in both co-expression network and protein-protein interaction (PPI) network were regarded as "real" hub genes. In another independent dataset, GSE52790, four genes were still significantly down-regulated in PBMCs from MDD patients compared with the controls. Furthermore, these four genes were validated by quantitative real-time polymerase chain reaction (qRT-PCR) in PBMCs from 33 MDD patients and 41 healthy controls. The qRT-PCR analysis showed that ATP synthase membrane subunit c locus 1 (ATP5G1) was significantly down-regulated in samples from MDD patients than in control samples (t = -2.89, p-value = 0.005). Moreover, this gene was significantly differentially expressed between patients and controls in the prefrontal cortex (z = -2.83, p-value = 0.005). Highly significant differentially methylated positions were identified in the Brodmann area 25 (BA25), with probes in the ATP5G1 gene being significantly associated with MDD: cg25495775 (t = 2.82, p-value = 0.008), cg25856120 (t = -2.23, p-value = 0.033), and cg23708347 (t = -2.24, p-value = 0.032). These findings indicate that the ATP5G1 gene is associated with the pathogenesis of MDD and that it could serve as a peripheral biomarker for MDD.

Efficacy and safety of bupropion hydrochloride extended-release versus escitalopram oxalate in Chinese patients with major depressive disorder: Results from a randomized, double-blind, non-inferiority trial.

BACKGROUND: This study evaluated the non-inferiority of bupropion extended-release (XL) compared to escitalopram for acute-phase treatment of Chinese patients with major depressive disorder (MDD). METHODS: This randomized (1:1), double-blind, active-control study conducted between February 2015 and October 2016 included patients with MDD (DSM-IV) (N = 538). The treatment phase had three dose levels (level 1 [Week 1], level 2 [Week 2-4], and level 3 [Week 5-8]), which included either bupropion XL 150 mg, 300 mg, 300 mg or escitalopram 10 mg, 10 mg, 10-20 mg (once-daily), respectively. Primary outcome was mean change from baseline in Hamilton Depression Rating Scale-17 (HAMD-17) total score at Week 8. RESULTS: Overall, 534 patients (bupropion XL, n = 266; escitalopram, n = 268) received at least one dose of study medication. The least square mean (standard error) change from baseline in HAMD-17 total score at Week 8 was -14.5 (0.41) in bupropion XL group and -15.4 (0.39) in escitalopram group (mean difference: 0.8 [-0.27, 1.94]). The response rate was 69.6% versus 72.9%, remission rate was 39.7% versus 47.2%, sustained response rate was 51.6% versus 56.3%, and sustained remission rate was 25.5% versus 28.6%, respectively, for bupropion XL versus escitalopram group. Adverse events were reported by 313 patients (bupropion XL, n = 157; escitalopram, n = 156); the most common on-treatment adverse event in both groups was nausea (10.5% versus 18.7%, respectively). LIMITATIONS: A non-inferiority short-term (8 weeks) study without a placebo arm. CONCLUSION: Results from this study demonstrated that the efficacy of bupropion XL was non-inferior to that of escitalopram in Chinese patients with MDD.