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.

Plasma metabolomics of schizophrenia with cognitive impairment: A pilot study.

Schizophrenia (SCZ) acts as a complex and burdensome disease, in which the functional outcome can be validly predicted by cognitive impairment, as one of the core features. However, there still lack considerable markers of cognitive deficits in SCZ. Based on metabolomics, it is expected to identify different metabolic characteristics of SCZ with cognitive impairment. In the present study, 17 SCZ patients with cognitive impairment (CI), 17 matched SCZ patients with cognitive normal (CN), and 20 healthy control subjects (HC) were recruited, whose plasma metabolites were measured using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The result of metabolic profiling indicated the identification of 46 differentially expressed metabolites between HC, CN, and CI groups, with 7 differentially expressed metabolites between CN and CI groups. Four differential metabolites (imidazolepropionic acid, Homoserine, and Aspartic acid) were repeatedly found in both screenings, by which the formed biomarker panel could discriminate SCZ with cognitive impairment from matched patients (AUC = 0.974) and health control (AUC = 0.841), respectively. Several significant metabolic pathways were highlighted in pathway analysis, involving Alanine, aspartate and glutamate metabolism, D-glutamine and D-glutamate metabolism, and Citrate cycle (TCA cycle). In this study, several differentially expressed metabolites were identified in SCZ with cognitive impairment, providing novel insights into clinical treatment strategies.

Comorbidity and Treatment in Older Psychiatric In-patients-A Retrospective Study in a Chinese Psychiatric Hospital.

Background: Comorbid somatic diseases increase the death risk and affect the condition, treatment, and prognosis of older psychiatric patients. We investigated the comorbidity and drug treatment in older patients with psychosis. Methods: This retrospective study used data from 3,115 older psychiatric in-patients hospitalized at the Shanghai Mental Health Center Affiliated to Shanghai Jiaotong University School of Medicine, China discharged from 2005 to 2015. Descriptive analyses of patients' age, sex, treatment drugs, diagnoses (based on ICD-10), and time trend were performed. Results: Patients' median age was 56 (range, 50-98) years; 1,824 (58.6%) were female. The top five first-level diagnoses were schizophrenia (F20) (n = 1,818, 58.3%), depressive episode (F32) (n = 457, 14.6%), bipolar affective disorder (F31) (n = 151, 4.8%), manic episode (F30), (n = 143, 4.6%), and vascular dementia (F01) (n = 136, 4.4%). Mental (99.9%), central nervous system (85.2%), digestive system (83.5%), cardiovascular system (72.5%), and anti-infective (59.6%) drugs had the highest prescription rates. The combined use of antidepressants, anti-anxiety, anti-arrhythmic, hormones and endocrine system drugs were significantly higher in female than in male patients, while mood stabilizers and genitourinary system drugs significantly more frequent in men. With increasing age, the F20-F29 patients decreased, while F00-F09 patients increased, with the corresponding changes to prescription in those patients. In comparison to that in 2005-2010, the combined prescriptions for genitourinary and cardiovascular drugs increased between 2011 and 2015, and F00-F09 and F40-F48 older patients doubled, accordingly anti-Alzheimer's disease drugs and antidepressants more than doubled. F30-F39 patients increased by 49.1%, and anti-anxiety drugs, mood stabilizers, etc. increased by ≥50%; F20-F29 older patients decreased by 26.7%, while antipsychotics only increased by 4.4%. Conclusions: This study found the combined drug treatment of somatic diseases, particularly for central nervous, digestive, cardiovascular, respiratory and genitourinary drugs were extremely common among older psychiatric in-patients in China. With increasing age, the F20-F29 patients decreased, while F00-F09 patients increased; the antipsychotics prescriptions decreased, and almost all comorbidity drugs increased. Compared with that in 2005-2010, the older patients with all diagnosis except F20-F29 increased in 2011-2015, and the prescriptions for psychotropic, genitourinary, and cardiovascular drugs increased.

Effects of the combination of second-generation antipsychotics on serum concentrations of aripiprazole and dehydroaripiprazole in Chinese patients with schizophrenia.

BACKGROUND: Aripiprazole (ARI) is often prescribed alone or in combination with other second-generation antipsychotics (SGAs) to treat patients with schizophrenia. However, this may increase the potential clinical significance of drug-drug interactions. Therapeutic drug monitoring (TDM) is an important and fundamental tool both when administering ARI alone and in combination with other SGAs to monitor ARI pharmacokinetics, adjust the dosage and thereby achieve more effective and safer treatment. AIMS: This study retrospectively investigated the effects of four SGA comedications (clozapine, risperidone, quetiapine (QTP) and olanzapine) and other potential factors (sex, age and ARI dose) on the serum concentrations of ARI and dehydroaripiprazole (DARI) in Chinese patients with schizophrenia using TDM data. METHODS: High-performance liquid chromatography was used to test the serum concentrations of ARI, DARI and ARI+DARI. In addition, steady-state dose-adjusted serum concentrations (ie, concentration-to-dose ratios, C:D ratios) of ARI, DARI and ARI+DARI; sex; age; ARI dose and SGA comedication dose between 299 inpatients with schizophrenia who received ARI or SGA comedication were all collected and analysed. Spearman's correlation and multiple linear regression analysis were used to evaluate bivariate associations between ARI dose and serum ARI and DARI concentrations and describe the effect of independent variables on serum ARI and DARI concentrations, respectively. RESULTS: There were significant differences in the C:D ratios of ARI (χ2=-3.21, p=0.001) and ARI+DARI (χ2=-2.50, p=0.01) between the ARI and SGA groups, as well as in the C:D ratios of ARI (χ2=-3.59, p<0.001) and ARI+DARI (χ2=-3.10, p=0.002) between the female patients in the two groups. Of the four SGAs, only QTP had significant effects on the C:D ratios of ARI (Z=-4.12, p<0.001) and ARI+DARI (Z=-3.62, p<0.001) when compared with the ARI group in the whole sample and on the C:D ratios of ARI, DARI and ARI+DARI (Z=-3.96, p<0.001; Z=-2.22, p=0.03; Z=-3.75, p<0.001, respectively) in women when compared with their counterparts in the ARI group. CONCLUSION: Comedication with SGAs resulted in lower C:D ratios of ARI and ARI+DARI compared with ARI monotherapy, and comedication with QTP resulted in lower C:D ratios of ARI and ARI+DARI than ARI monotherapy. Despite this statistical significance of our findings, whether the presently observed effect has clinical significance requires exploration by further research. TDM and dosage regulation of ARI should be performed in Chinese inpatients with schizophrenia who are receiving SGA comedication (especially QTP) to maintain a safe and effective dose-adjusted serum concentration of ARI and DARI.

Hair Cortisol Is Associated With Social Support and Symptoms in Schizophrenia.

INTRODUCTION: Psychosocial stressors may worsen psychotic symptoms in schizophrenia, while social support could protect against the effects of stress in schizophrenia. Hypothalamus-pituitary-adrenal axis dysfunction has been associated with schizophrenia. Hair cortisol concentrations (HCC) allow assessment of cumulative cortisol secretion over the preceding 3 months. The relationship between HCC, psychosocial stressors, social support, and the clinical characteristics of schizophrenia needs to be explored. METHODS: One hundred nine schizophrenia patients and 86 healthy controls between the ages of 18 and 60 were enrolled in the study. Three-centimeter samples of hair were collected from the scalp and HCC were measured using ELISA kits. Linear regression and factor analysis were employed to examine the relationship between HCC, childhood trauma, the number of stressful life events (SLE), the amount of social support in the 3 months prior to the hair cortisol assessment and clinical characteristics of schizophrenia. RESULTS: Schizophrenia patients experience more SLE in their lifetime, receive less social support, and have lower HCC in the recent 3 months compared to healthy controls. In the schizophrenia patients, HCC are positively associated with the amount of social support and negatively associated with the severity of delusions. The interaction between social support and SLE predicts decreased HCC. Factor analysis shows that a subgroup of schizophrenia patients who experience childhood trauma and SLE are characterized by decreased HCC. CONCLUSIONS: Findings indicate social support could be a moderator for the relationship between SLE and HCC which may attenuate the effects of SLE in schizophrenia.

Lack of Association Between PLA2G6 Genetic Variation and Parkinson's Disease: A Systematic Review.

BACKGROUND: The phospholipase A2 Group 6 (PLA2G6, also known as PLA2, PARK14, and iPLA2) gene encodes a group VIA calcium-independent phospholipase A2. Genetic polymorphism of PLA2G6 has been indicated to be involved in conferring susceptibility for Parkinson's disease (PD), whereas conclusive results have not been obtained. Thus, we intended to conduct a systematic review to determine if PLA2G6 genetic variation confers a greater susceptibility to PD. METHODS: All case-control studies that investigated the association of the PLA2G6 polymorphisms with the risk of PD published before 15 July 2018 were included. The literature was comprehensively searched and identified in five English databases (EBSCO, Pubmed, OVID, EMBASE and ISI Web of Knowledge) and four Chinese databases (Wanfang database, Chinese Biomedical Literature Database, China Academic Journals Database and VIP database). We performed analyses of study characteristics, heterogeneity, and forest plot in analyses analogous to dominant, codominant and additive models with the pooled odds ratio (OR) in fixed- or random-effects models as the measure of association. RESULTS: A total of 664 potentially relevant studies were retrieved with the initial search, of which eight studies fulfilled the inclusion criteria, and included 2,779 PD patients and 3,291 control participants,. Among all the reported 27 genetic variants, 15 single nucleotide polymorphisms (SNPs) were present only in patients, and only five available SNPs (rs2267369, rs140758033, c.1959T>A (Gly653Gly), rs76718524, rs199935023) were pooled in the meta-analysis. However, there was no evidence for a significant association between the five SNPs and PD risk in dominant, codominant and allele models, suggesting a lack of association between PLA2G6 genetic variation and PD susceptibility. CONCLUSION: The present study assessed the association of PLA2G6 genetic polymorphism with the risk PD, and the result strongly demonstrates that PLA2G6 polymorphism is not associated with PD susceptibility.

Sesquiterpenoids and γ-pyranone derivatives from the whole plant of Erigeron breviscapus and their neuroprotective effects.

Four new sesquiterpenes (1-2, 6-7), a new pyranone glycoside (10) along with six known compounds, were isolated from the whole plant of Erigeron breviscapus. Their planar structures were elucidated using extensive spectroscopic analyses. Brevisterpene A (1) and brevisterpene B (2) were proved to be a pair of diastereomer followed by mixtures resolution using chiral HPLC. Their absolute configurations were determined by ECD calculation. The relative configuration of brevisnoside B (7) was elucidated by a combined analysis of NOESY spectrum and computation of 13C NMR chemical shifts, and determination of the absolute configurations of 6 and 7 assisted by optical rotation calculations. Compounds 1 and 2 displayed moderate neuroprotective effects against H2O2-induced damage in SH-SY5Y cells.

Correlation of hair risperidone concentration and serum level among patients with schizophrenia.

BACKGROUND: Risperidone (RSP) has a rapid onset in vivo, low dosage and high plasma protein binding rate, therefore therapeutic drug monitoring (TDM) is needed to ensure safety in clinical treatment. However, compared with blood, hair is non-invasive, safe, non-infectious and easy to transport and store. AIMS: This study aims to investigate the correlations among the drug concentrations of RSP in hair and serum, which provides an experimental basis to explore hair as a novel biomaterial to meet the needs of clinical detection. METHODS: 34 patients with schizophrenia treated with RSP for more than 3 months were enrolled in this study. About 1 cm section of hair near the scalp was taken from the subjects, pretreated and detected by liquid chromatography-mass spectrometry. A correlation analysis was conducted among the drug concentrations in hair, the serum concentrations and the daily dosage. The data were analysed using SPSS 20.0 software. RESULTS: There was significant correlation between the hair concentration of RSP (two-tailed test, r=0.440, p=0.009) with the serum concentration of RSP, and the hair concentration of 9-hydroxyrisperidone (9-HR) with the serum concentration of 9-HR had no significant correlation (two-tailed test, r=-0.217, p=0.217); the total concentration of the RSP and 9-HR had no significant correlation between hair and serum (r=0.227, p=0.196). The dosage had no statistically significant correlation with the concentration of RSP in hair (r=0.207, p=0.241), 9-HR in hair (r=-0.194, p=0.271) and the total concentration of RSP and 9-HR in hair (r=0.188, p=0.288). There was no statistical correlation between the dosage and the concentration of RSP in serum (r=-0.059, p=0.741), but significant correlation between the dosage and 9-HR in serum (r=0.581 p<0.001) was found, and the correlation between the dosage and the total concentration of the two drugs RSP and 9-HR in serum was also significant (r=0.437, p=0.01). CONCLUSION: The correlation analysis showed that the concentration of RSP in hair was statistically significant with the serum RSP concentration. In this study, we provided some experimental basis for hair as a new biomaterial to monitor the therapeutic drug concentration.

Identification of plasma biomarkers for distinguishing bipolar depression from major depressive disorder by iTRAQ-coupled LC-MS/MS and bioinformatics analysis.

It is important to differentiate between bipolar disorder (BD) and major depressive disorder (MDD) in the first depressive episode because of the potential treatment implications. Previous studies have mainly focused on the different clinical features or pathological biomarkers to distinguish these two diseases; however, a better understanding of the proteomics profiling of BD may help aid future therapeutic strategies. Here, we applied isobaric tags for relative and absolute quantification (iTRAQ) technology combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify differentially expressed proteins between MDD and bipolar depression (BP). In total, 30 MDD, 30 BP and 30 healthy subjects were included. Proteins from depleted plasma samples were digested into peptides, individually labeled with iTRAQ reagents, combined and subjected to LC-MS/MS and further bioinformatics analyses. Our results showed that 9 proteins were significantly altered between MDD and BP. Briefly, B2RAN2, B4E1B2, APOA1, ENG, SBSN and QSOX2 were up-regulated, whereas ORM1, MRC2 and SLPI were down-regulated. Most identified proteins were related to the immune system. The bioinformatics analysis showed that B2RAN2 (highly similar to vanin-1) was involved in the significantly enriched KEGG pathways "pantothenate and CoA biosynthesis" (P=0.009). B2RAN2 and ENG may play important roles in depression. They may serve as candidate biomarkers for distinguishing MDD and BP. Further validation and investigation are required to illuminate the roles of B2RAN2 and ENG in MDD and BP. The current study provided a potential and novel biomarker panel that may, in turn, aid the diagnosis of BD.

NR4A2 genetic variation and Parkinson's disease: Evidence from a systematic review and meta-analysis.

INTRODUCTION: The homo sapiens nuclear receptor subfamily 4, group A (NR4A2) genetic variation has been implicated as a risk factor for Parkinson's disease (PD). Nevertheless, the results are inconclusive. We conducted a comprehensive systematic review and meta-analysis to quantify the impact of NR4A2 variation on the risk of PD. METHODS: All eligible case-control studies published up to June 2016 by searching Pubmed, OVID, EBSCO, PsycINFO, ISI Web of Knowledge, Chinese Biomedical Literature Database and China Academic Journals Database were identified. Pooled odds ratio (OR) with 95% confidence interval (CI) were used to access the strength of the association in fixed- or random-effects model. RESULTS: Eighteen studies reported 24 genetic variants with a total of 6150 cases and 5919 controls were included. Twelve studies for NR4A2 rs35479735 polymorphism and 4 studies for rs12803 were available for meta-analysis. A significant association was observed for rs35479735 under the homozygous model (OR=1.31, 95% CI: 1.10-1.56, P=0.003), whereas no significant association for rs12803 was detected. In subgroup analysis stratified by ethnicity, age onset and familial history, we found no significant association except one in sporadic PD subgroup under the recessive (OR=3.30, 95% CI: 1.23-8.84, P=0.02) and homozygous model (OR=3.43, 95% CI: 1.26-9.33, P=0.02) for rs35479735. CONCLUSION: The study comprehensively evaluated the association of NR4A2 variation with PD, and the results failed to demonstrate that the NR4A2 polymorphisms significantly associated with PD except for rs35479735, suggesting that more studies are needed to elucidate if NR4A2 is a risk of PD.

A new triterpenoid from Panax ginseng exhibits cytotoxicity through p53 and the caspase signaling pathway in the HepG2 cell line.

A new triterpenoid, 20(R),22(xi),24(S)-dammar-25(26)-ene-3beta,6 alpha,12 beta,20,22,24-hexanol (1), and three known triterpenoids, beta-D-glucopyranoside,(3beta,12 beta)-12,20-dihydroxydammar-24-en-3-yl,6-acetate (2), 20(R)-ginsenoside Rg3 (3), and 20(R)-ginsenoside Rh2 (4), were isolated from the leaves of Panax ginseng. Their structures were determined by chemical analysis and spectral methods (IR, 1D and 2D NMR, HR-ESI-MS). Compounds 1-4 were exhibited various degrees of cytotoxicity in the human hepatoma cell line, HepG2. Compound 1 had the highest cytotoxic potency, with an IC50 value of 20.1 microM, by stimulating p53-mediated cell cycle arrest at the G1 to S phase transition, leading to apoptosis via activation of the caspase signaling pathway.