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Background: Schizophrenia is a debilitating condition that affects 1% of the global population. Understanding the prevalence and the factors predicting schizophrenia remission is crucial for healthcare providers. This study aimed to determine the prevalence of remission and factors affecting the remission. Cross-sectional study was conducted at the Amanuel Mental Specialized Hospital from 3 October, 2022, to 31 August, 2023, and included 271 participants. Remission was measured using Remission in Schizophrenia Working Group (RSWG) symptom severity-based criteria. Data analysis was done using SPSS V.25. Results: The mean age of participants was 34.2 with standard deviation (SD) of 10.5 years. Most were male (90%), unmarried (63.8%), lived with their relatives (91.9%), and were unemployed (56.5%). Fifty-two percent achieved symptomatic remission. Remission in patients with medication switched to SGAs increased by 1.9 times compared to patients without medication switch (AOR 1.9, 95% CI: 1.1, 1.2). Adherent patients had 2.7 times higher odds of symptomatic remission as compared to non-adherent patients (AOR 2.7, 95% CI: 1.5,4.9), and for each unit increase in body mass index (BMI), the odds of achieving symptomatic remission were increased by 13% (AOR 1.13, 95% CI: 1.04, 1.23). The odds of symptomatic remission decreased by 71% in patients experiencing moderate-to-severe side effects compared to their counterparts (AOR 0.29, 95% CI: 0.1, 0.6). Conclusions: Our study revealed a symptomatic remission was achieved in 141 (52%) of the subjects. There is a possibility to improve symptomatic remission with counseling on the importance of adherence, monitoring and managing side effects, and switching medication to either risperidone or olanzapine. Measuring remission using RSWG time-based criteria is recommended. [ABSTRACT FROM AUTHOR]

Schizophrenia spectrum disorders (SSD) are a group of diseases characterized by one or more abnormal features in perception, thought processing and behavior. Patients suffering from SSD are at risk of developing life-threatening complications. Pharmacogenetic studies have shown promising results on personalized treatment of psychosis. In the current study, 103 patients diagnosed with SSD treated with risperidone as antipsychotic monotherapy were enrolled. Socio-demographics and clinical data were recorded, and laboratory tests and genotyping standard procedure for cytochrome P450 (CYP) 2D6*4 were performed. Patients were evaluated by the Positive and Negative Syndrome Scale (PANSS) on admission and at discharge. Based on the reduction in the PANSS total score, subjects were divided into non-responders, partial responders and full responders. Only 11 subjects had a full response to risperidone (10.67%), 53 subjects (51.45%) had a partial response, and 39 participants (37.86%) were non-responders. Patients at first episode psychosis showed significantly higher levels of blood glucose and prolactin levels, while chronic patients showed significantly higher LDL levels. Adverse drug reactions (ADR) such as tremor and stiffness significantly correlated with genetic phenotypes (p = 0.0145). While CYP2D6 showed no impact on treatment response, ADR were significantly more frequent among poor and intermediate metabolizers. [ABSTRACT FROM AUTHOR]

The current research aims to develop thermosensitive polymeric micelles loaded with risperidone for nasal administration, emphasizing the added benefits of their thermosensitive behavior under nasal conditions. An initial risk assessment facilitated the advanced development process, confirming that the key indicators of thermosensitivity were suitable for nasal application. The polymeric micelles exhibited an average size of 118.4 ± 3.1 nm at ambient temperature and a size of 20.47 ± 1.2 nm at 36.5 °C, in both cases in monodisperse distribution. Factors such as pH and viscosity did not significantly impact these parameters, demonstrating appropriate nasal applicability. The model formulations showed a rapid, burst-like drug release profile in vitro, accompanied by a quick and high permeation rate at nasal conditions. Overall, the Quality by Design-based risk assessment process led to the development of an advanced drug delivery system capable of administering risperidone through the nasal cavity. [ABSTRACT FROM AUTHOR]

Microglia are the primary innate immune cells of the central nervous system and extensively contribute to brain homeostasis. Dysfunctional or excessive activity of microglia may be associated with several neuropsychiatric disorders, including schizophrenia. Therefore, we examined whether aripiprazole and risperidone could influence the expression of the Cd200–Cd200r and Cx3cl1–Cx3cr1 axes, which are crucial for the regulation of microglial activity and interactions of these cells with neurons. Additionally, we evaluated the impact of these drugs on microglial pro- and anti-inflammatory markers (Cd40, Il-1β, Il-6, Cebpb, Cd206, Arg1, Il-10 and Tgf-β) and cytokine release (IL-6, IL-10). The research was executed in organotypic cortical cultures (OCCs) prepared from the offspring of control rats (control OCCs) or those exposed to maternal immune activation (MIA OCCs), which allows for the exploration of schizophrenia-like disturbances in animals. All experiments were performed under basal conditions and after additional stimulation with lipopolysaccharide (LPS), following the "two-hit" hypothesis of schizophrenia. We found that MIA diminished the mRNA level of Cd200r and affected the OCCs' response to additional LPS exposure in terms of this parameter. LPS downregulated the Cx3cr1 expression and profoundly changed the mRNA levels of pro- and anti-inflammatory microglial markers in both types of OCCs. Risperidone increased Cd200 expression in MIA OCCs, while aripiprazole treatment elevated the gene levels of the Cx3cl1–Cx3cr1 dyad in control OCCs. The antipsychotics limited the LPS-generated increase in the expression of proinflammatory factors (Il-1β and Il-6) and enhanced the mRNA levels of anti-inflammatory components (Cd206 and Tgf-β) of microglial polarization, mostly in the absence of the MIA procedure. Finally, we observed a more pronounced modulating impact of aripiprazole on the expression of pro- and anti-inflammatory cytokines when compared to risperidone in MIA OCCs. In conclusion, our data suggest that MIA might influence microglial activation and crosstalk of microglial cells with neurons, whereas aripiprazole and risperidone could beneficially affect these changes in OCCs. [ABSTRACT FROM AUTHOR]

Background: Induced pluripotent stem cell (iPSC) based neuronal differentiation is valuable for studying neuropsychiatric disorders and pharmacological mechanisms at the cellular level. We aimed to examine the effects of typical and atypical antipsychotics on human iPSC-derived neural progenitor cells (NPCs). Methods: Proliferation and neurite outgrowth were measured by live cell imaging, and gene expression levels related to neuronal identity were analyzed by RT-QPCR and immunocytochemistry during differentiation into hippocampal dentate gyrus granule cells following treatment of low- and high-dose antipsychotics (haloperidol, olanzapine, and risperidone). Results: Antipsychotics did not modify the growth properties of NPCs after 3 days of treatment. However, the characteristics of neurite outgrowth changed significantly in response to haloperidol and olanzapine. After three weeks of differentiation, mRNA expression levels of the selected neuronal markers increased (except for MAP2), while antipsychotics caused only subtle changes. Additionally, we found no changes in MAP2 or GFAP protein expression levels as a result of antipsychotic treatment. Conclusions: Altogether, antipsychotic medications promoted neurogenesis in vitro by influencing neurite outgrowth rather than changing cell survival or gene expression. This study provides insights into the effects of antipsychotics on neuronal differentiation and highlights the importance of considering neurite outgrowth as a potential target of action. [ABSTRACT FROM AUTHOR]

Objective: Previous studies have suggested that the suicide rate of patients with schizophrenia is high. This study investigates factors influencing suicidal ideation in first‐episode schizophrenia patients, focusing on cognitive function, brain‐derived neurotrophic factor (BDNF), triglyceride (TG), and total cholesterol (TC) in patients with first‐episode schizophrenia. Methods: A total of 123 patients with first‐episode schizophrenia and 38 healthy controls were included in the study. The patients were divided into suicidal and nonsuicidal ideation groups based on the Beck Scale for Suicidal Ideation, and they were assessed with Positive and Negative Syndrome Scale (PANSS). Cognitive function was assessed using the Chinese version of the MATRICS consensus cognitive battery (MCCB) and the serum BDNF, TG, and TC were detected. The main statistical methods include t‐test, χ2 test, multivariate logistic regression analysis, receiver operating characteristic (ROC) curve analysis, and the DeLong test. Results: 26.02% of patients exhibited suicidal ideation. Higher PANSS and TC levels were risk factors, while higher MCCB scores and BDNF levels were protective factors. ROC analysis indicated AUCs of 0.630, 0.724, and 0.762 for serum BDNF, PANSS, and MCCB, respectively, with a combined AUC of 0.870. Conclusion: Serum BDNF level, PANSS score, and MCCB score can be used as auxiliary predictors of suicidal ideation in schizophrenic patients. Combining these three indicators can effectively predict suicidal ideation in schizophrenic patients. [ABSTRACT FROM AUTHOR]

Background: Sudden unexplained death in individuals with mental health problems was described in 1960 and a link with antipsychotic drugs was postulated over 40 years ago. Down the years, a clear relation between electrocardiography (ECG) abnormalities and antipsychotic use was observed with special emphasis on QT prolongation. Various factors modulate the risk of QT prolongation including gender, age, race, and drug choice. An evaluation of antipsychotic use-induced QT changes in Eastern Indian population is the dire need of the hour. Aims and Objectives: The aim and objective are to study the effects of risperidone, olanzapine, and aripiprazole on QT interval after a period of 4 weeks of usage in previously drug-naïve Eastern Indian psychotic patients. Materials and Methods: A total of 78 drug-naïve patients fulfilling inclusion and exclusion criteria were randomly assigned to receive risperidone, olanzapine, and aripiprazole after a baseline ECG. A repeat ECG after 4 weeks of drug usage was done and compared using standard protocols with respect to QT interval. Findings were tabulated and statistical analysis was done using SPSS 25.0 to test for statistical significance at P<0.05. Results: Our study found significant rise in QT values after 4 weeks of using olanzapine and aripiprazole, but not with risperidone. However, none of the patients from either of the groups experienced any incidence of QT prolongation. Rise with olanzapine was significantly higher than that with risperidone. Conclusion: Caution is suggested in patients with risk factors for QT prolongation or a high value of QT during prescribing olanzapine. Studies with larger sample size can be carried out to find genetic predisposition of Indian population to anti-psychotic induced QT interval rise/prolongation. [ABSTRACT FROM AUTHOR]

Aims: We aimed to evaluate the potential of a novel selective α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole‐propionic acid receptor (AMPAR) potentiator, LT‐102, in treating cognitive impairments associated with schizophrenia (CIAS) and elucidating its mechanism of action. Methods: The activity of LT‐102 was examined by Ca2+ influx assays and patch‐clamp in rat primary hippocampal neurons. The structure of the complex was determined by X‐ray crystallography. The selectivity of LT‐102 was evaluated by hERG tail current recording and kinase‐inhibition assays. The electrophysiological characterization of LT‐102 was characterized by patch‐clamp recording in mouse hippocampal slices. The expression and phosphorylation levels of proteins were examined by Western blotting. Cognitive function was assessed using the Morris water maze and novel object recognition tests. Results: LT‐102 is a novel and selective AMPAR potentiator with little agonistic effect, which binds to the allosteric site formed by the intradimer interface of AMPAR's GluA2 subunit. Treatment with LT‐102 facilitated long‐term potentiation in mouse hippocampal slices and reversed cognitive deficits in a phencyclidine‐induced mouse model. Additionally, LT‐102 treatment increased the protein level of brain‐derived neurotrophic factor and the phosphorylation of GluA1 in primary neurons and hippocampal tissues. Conclusion: We conclude that LT‐102 ameliorates cognitive impairments in a phencyclidine‐induced model of schizophrenia by enhancing synaptic function, which could make it a potential therapeutic candidate for CIAS. [ABSTRACT FROM AUTHOR]

Introduction: RYKINDO® (Rykindo) is a novel, long-acting injectable risperidone formulation administered biweekly (Q2W) through intramuscular gluteal injection for the treatment of schizophrenia in adult patients. This analysis was conducted to demonstrate that the clinical outcomes of Rykindo are equivalent to those of RISPERDAL CONSTA® (Consta; Q2W), and to establish a dosing methodology to switch from Consta to Rykindo, as well as to introduce Rykindo to patients who are currently on oral RISPERDAL® (Risperdal). Methods: Population pharmacokinetic (PK) models for Rykindo and Consta were developed using a nonlinear mixed-effects model with the data from phase 1 studies. A model-based simulation was also conducted using NONMEM. Results: The PK profiles of Rykindo and Consta were adequately represented by a one-compartment model with an immediate release followed by an intermediate and third main release. Drug release of Rykindo was faster than for Consta, reaching steady state approximately 2–3 weeks earlier. The exposures of the active moiety of Rykindo and Consta were comparable at steady state. Model-based simulation indicated that switching from Consta to Rykindo requires administration of the first Rykindo injection within 4–5 weeks following the last Consta injection. For patients taking Risperdal, introducing Rykindo with 1 week of Risperdal supplemental for once-daily dosing (QD) can achieve comparable or superior exposure to that of Consta with 3 weeks of oral QD supplements. A dosing window of ± 3 days for Rykindo was recommended. Conclusions: This established approach provides guidance to physicians to initiate Rykindo therapy in adult patients with schizophrenia. Trial Registration: ClinicalTrials.gov identifier, NCT02055287, NCT02186769 and NCT02091388. [ABSTRACT FROM AUTHOR]

Aims: The extensive variability in cytochrome P450 2D6 (CYP2D6) metabolism is mainly caused by genetic polymorphisms. However, there is large, unexplained variability in CYP2D6 metabolism within CYP2D6 genotype subgroups. Solanidine, a dietary compound found in potatoes, is a promising phenotype biomarker predicting individual CYP2D6 metabolism. The aim of this study was to investigate the correlation between solanidine metabolism and the CYP2D6‐mediated metabolism of risperidone in patients with known CYP2D6 genotypes. Methods: The study included therapeutic drug monitoring (TDM) data from CYP2D6‐genotyped patients treated with risperidone. Risperidone and 9‐hydroxyrisperidone levels were determined during TDM, and reprocessing of the respective TDM full‐scan high‐resolution mass spectrometry files was applied for semi‐quantitative measurements of solanidine and five metabolites (M402, M414, M416, M440 and M444). Spearman's tests determined the correlations between solanidine metabolic ratios (MRs) and the 9‐hydroxyrisperidone‐to‐risperidone ratio. Results: A total of 229 patients were included. Highly significant, positive correlationswere observed between all solanidine MRs and the 9‐hydroxyrisperidone‐to‐risperidone ratio (ρ > 0.6, P <.0001). The strongest correlation was observed for the M444‐to‐solanidine MR in patients with functional CYP2D6 metabolism, i.e., genotype activity scores of 1 and 1.5 (ρ 0.72–0.77, P <.0001). Conclusion: The present study shows strong, positive correlations between solanidine metabolism and CYP2D6‐mediated risperidone metabolism. The strong correlation within patients carrying CYP2D6 genotypes encoding functional CYP2D6 metabolism suggests that solanidine metabolism may predict individual CYP2D6 metabolism, and hence potentially improve personalized dosing of drugs metabolized by CYP2D6. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the role of Brain derived neurotrophic factor (BDNF) in the psychotic symptoms in first‐episode patients with schizophrenia and whether BDNF levels were associated with the improvement of psychotic symptoms after risperidone treatment. Methods: 89 schizophrenia patients and 90 healthy controls were recruited, the schizophrenia patients were assigned into early response or early non‐response groups at 2 weeks based on improvement in the positive and negative symptoms scale (PANSS) total score. All patients were treated with risperidone for 2 weeks, their serum BDNF levels were compared at baseline and after 2 weeks treatment. Results: We found that patients had lower BDNF levels, compared to controls at baseline. After 2 weeks of treatment of risperidone, BDNF levels were significantly increased and psychotic symptoms were decreased in early response group. Correlation analysis showed that the change of BDNF levels after treatment was correlated with the change of PANSS total score. Further regression analysis showed that the change in BDNF levels was an independent predictor for the improvement in psychotic symptoms. Conclusions: Our findings reveal that the level of BDNF was lower in first‐episode schizophrenic patients, moreover, the changes in serum BDNF levels may have a predictive effect on the early improvement in psychotic symptoms in the first 2 weeks. [ABSTRACT FROM AUTHOR]

Background: Quetiapine is commonly prescribed off-label to manage delirium in intensive care unit (ICU) patients. However, limited studies comparing its efficacy and safety to those of other antipsychotics exist in the literature. Method: A retrospective, single-center chart review study was conducted on adults admitted to the ICU between January 2017 and August 2022, who were diagnosed with delirium and treated with a single antipsychotic and had no neurological medical conditions, active alcohol withdrawal, or prior use of antipsychotics. Data were analyzed using SPSS software version 28, with p-values of <0.05 indicating statistical significance. Results: In total, 47 patients were included, of whom 22 (46.8%), 19 (40.4%), 4 (8.5%), and 2 (4.3%) were on quetiapine, haloperidol, risperidone, and olanzapine, respectively. The median number of hours needed to resolve delirium were 12 (21.5), 23 (28), 13 (13.75), and 36 (10) (p = 0.115) for quetiapine, haloperidol, risperidone, and olanzapine, respectively, with haloperidol being used for a significantly shorter median number of days than quetiapine (3 (2.5) days vs. 7.5 (11.5) days; p = 0.007). Of the medication groups, only quetiapine-treated patients received a significantly higher median maintenance compared to the initiation dose (50 (50) mg vs. 50 (43.75) mg; p = 0.039). For the length of stay in the ICU and hospital, delirium-free days, % of ICU time spent in delirium, ventilator-free days, the difference between the highest and baseline QTc intervals, and ICU and hospital mortalities, no significant difference was observed between the groups. Conclusions: Overall, the use of quetiapine in our retrospective study seems to not be advantageous over the other drugs in terms of efficacy and safety outcomes. [ABSTRACT FROM AUTHOR]

Dopamine and serotonin receptors and transporters play an essential role in the pathophysiology of schizophrenia; changes in their expression have been reported in neurons and leukocytes. Each antipsychotic induces a unique pattern in leukocyte function and phenotype. However, the use of polytherapy to treat schizophrenia makes it challenging to determine the specific effects of risperidone on peripheral blood mononuclear cells (PBMCs). The aim of this study was to evaluate the changes in the expression of D3, D5, DAT, 5-HT2A, and SERT in PBMCs from healthy volunteers (HV), drug-naive patients with schizophrenia (PWS), drug-free PWS, and PWS treated with risperidone for up to 40 weeks using quantitative PCR. Our study revealed elevated mRNA levels of D3, DAT, 5-HT2A, and SERT in unmedicated PWS. Treatment with risperidone led to a reduction only in the expression of 5-HT2A and SERT. Furthermore, we observed a moderate correlation between 5-HT2A expression and the positive and negative syndrome scale (PANSS), as well as SERT expression and PANSS scale. We also found a moderate correlation between 5-HT2A and SERT expression and the positive subscale. The duration of risperidone consumption had a significant negative correlation with the expression of 5-HT2A and SERT. Our study introduces the measurement of 5-HT2A and SERT expression in PBMCs as a useful parameter for assessing the response to risperidone in PWS. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This article discusses the molecular pharmacology of trace amine-associated receptor 1 (TAAR1) and its potential role in advancing antipsychotic drug discovery. Schizophrenia, a chronic mental disorder, is characterized by negative symptoms, positive symptoms, and cognitive impairment. Current antipsychotic drugs have limited efficacy and are associated with side effects. TAAR1 has emerged as a potential therapeutic target for psychiatric disorders, and recent studies have provided insights into the molecular mechanisms and activation characteristics of TAAR1. These findings could contribute to the development of new antipsychotic drugs. [Extracted from the article]

The article describes the case of a 60-year old woman who was diagnosed with normal pressure hydrocephalus and psychosis. The patient showed no significant improvement following prescription with quetiapine, haloperidol and valproate for her paranoid psychotic symptoms. Her gait disturbances and psychotic symptoms improved after a standard ventriculoperitoneal shunt procedure.

Background: To explore the influence of CYP2D6 genetic polymorphism on risperidone metabolism, thereby affecting risperidone's effects and safeties in patients with chronic schizophrenia. Methods: Sixty-nine subjects with chronic schizophrenia treated with risperidone were recruited. CYP2D6 genotypes was determined using targeted sequencing and translated into phenotype using activity system. Risperidone plasma concentrations were measured using HPLC. Positive and Negative Symptom Scale (PANSS) and Brief Psychiatric Rating Scale (BPRS) were used to evaluate the existence and severity of psychiatric symptoms, Barnes Akathisia Scale (BAS) and Extrapyramidal Symptom Rating Scale (ESRS) for neurological side effects. Metabolic and endocrine status assess were also included. Results: The plasma drug concentrations varied hugely among individuals. Intermediate metabolizer (IM) group had higher plasma levels of RIP and dose corrected RIP concentration, RIP/9-OH-RIP ratio and C/D ratio than normal metabolizer (NM) group (p < 0.01). There was no statistic difference between responders and non-responders in dose-adjusted plasma concentrations and ratios of RIP/9-OH-RIP and C/D. The occurrence of EPS was related to active moiety levels in 4th week (p < 0.05). The prolactin (PRL) levels in two follow-ups were both significantly higher than baseline (p < 0.01). PRL change from baseline to week 4 and week 8 were both positively associated with active moiety concentration detected in week 4 (p < 0.05). Conclusions: The risperidone plasma levels have great inter- and intraindividual variations, and are associated with the CYP2D6 phenotypes, as well as the changes in serum prolactin in patients diagnosed with chronic schizophrenia. [ABSTRACT FROM AUTHOR]

Objective: Recent evidence suggests that oxidative stress contributes to the pathophysiology of schizophrenia. This study aimed to compare thiol-disulphide homeostasis in acute and stable phases of schizophrenia for the first time. Methods: Among the patients with schizophrenia, 61 in the acute-phase and 61 in the stable phase of their illness were enrolled in the study. Native thiol (NT), total thiol (TT), disulphide (SS), disulphide/native thiol, disulphide/total thiol, and native thiol/total thiol for thiol-disulphide homeostasis were compared between the groups. The Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Positive/Negative Symptoms (SAPS/SANS), Clinical Global ImpressionSeverity Scale (CGI-S), Barnes Akathisia Rating Scale, and Simpson-Angus Scale were used to assess symptoms. Results: After controlling for age, sex, body mass index, and smoking status there were significant differences in NT, TT, SS/NT, SS/TT, and NT/TT, but not SS. Thiol/disulphide homeostasis has shifted in favour of the oxidative side in patients with acute-phase compared to that in stable schizophrenia. BPRS, SAPS, and CGI-S scores were significantly correlated with all six thiol-disulphide parameters, but not SANS, when controlling for age and sex. Significant receiver operating characteristic (ROC) curves were obtained for all thiol-disulphide homeostasis parameters. Discriminant analysis was found to be statistically significant in discriminating between groups. Conclusion: These results show that oxidative status increases thiol-disulphide homeostasis in patients with acute-phase schizophrenia compared to those with stable schizophrenia. These findings suggest that thiol-disulphide parameters can be used as biomarkers for the acute exacerbation of schizophrenia. [ABSTRACT FROM AUTHOR]

The retention profile of six serotonin receptor ligands such as arylpiperazines (aripiprazole, ziprasidone, risperidone), and benzothiazepine derivatives (olanzapine, mianserin, quetiapine), was investigated on C8 alkyl and pentafluorophenylpropyl stationary phases. The experimental design methodology was used to define their retention behavior and achieve acceptable separation results. Both phases showed satisfactory selectivity for all compounds. The optimal separation among the structurally related arylpiperazines and benzothiazepines was found with the C8 phase at 25°C, using acetonitrile (40%, v/v) and 20 mM ammonium acetate as a mobile phase modifier. The selectivity and sensitivity performances of the selected C8 system were discussed considering the separation of aripiprazole and its related compounds. In addition, the specified conditions were validated for determining aripiprazole in pharmaceutical dosage forms. The developed reversed-phase high-performance liquid chromatography method can be successfully used for the rapid chromatographic profiling of serotonin receptor ligands and related analogs, providing increased selectivity during pharmaceutical analysis. [ABSTRACT FROM AUTHOR]

Mental and behavioural disorders are prevalent worldwide. These conditions account for 12% of the global burden of disease 4. It is estimated that, they will account for the loss of 15% of the disability-adjusted life-years (DALYs). Globally, these illnesses have a point prevalence of about 10% for adults. After obtaining approval and clearance from the Institutional Ethical Committee, 320 cases were included for the present study. After obtaining the informed Consent from the patients/guardians, relevant data was recorded from patient's medical records and prescription orders. Among all the psychotropic drugs used, Risperidone had shown good improvement (n=88, 49.7%), Satisfactory improvement (n=39, 36.8%). Escitalopram showed good, satisfactory and best improvement in (25.4%), (41.5%) and (54.5%) of the population who were given the drug. Aminitriptyline and anticholinergic drug Trihexphenidyl also showed satisfactory results in terms of efficacy. [ABSTRACT FROM AUTHOR]

Anxiety and ejaculation share similar sympathetic neuronal pathways and hence they may coincide. In this case report, we describe a 30-year-old male with ongoing perceptual disturbances and spontaneous ejaculations that occur without sexual arousal. The patient ultimately benefited from pharmacological therapy with risperidone. [ABSTRACT FROM AUTHOR]

The article focuses on a case study of a 38-year-old male with craniopharyngioma who developed symptoms of obsessive-compulsive disorder (OCD) post-surgery, potentially due to disruption of brain circuits. Topics include the association between brain tumor characteristics and OCD symptomatology, the challenges in managing OCD symptoms post-neurosurgery, and the potential role of tumor regrowth in symptom persistence despite treatment efforts.

Transcranial magnetic stimulation (TMS) combined with electromyography (EMG) has widely been used as a non-invasive brain stimulation tool to assess excitation/inhibition (E/I) balance. E/I imbalance is a putative mechanism underlying symptoms in patients with schizophrenia. Combined TMS-electroencephalography (TMS-EEG) provides a detailed examination of cortical excitability to assess the pathophysiology of schizophrenia. This study aimed to investigate differences in TMS-evoked potentials (TEPs), TMS-related spectral perturbations (TRSP) and intertrial coherence (ITC) between patients with schizophrenia and healthy controls. TMS was applied over the motor cortex during EEG recording. Differences in TEPs, TRSP and ITC between the patient and healthy subjects were analysed for all electrodes at each time point, by applying multiple independent sample t-tests with a cluster-based permutation analysis to correct for multiple comparisons. Patients demonstrated significantly reduced amplitudes of early and late TEP components compared to healthy controls. Patients also showed a significant reduction of early delta (50–160 ms) and theta TRSP (30-250ms),followed by a reduction in alpha and beta suppression (220–560 ms; 190–420 ms). Patients showed a reduction of both early (50–110 ms) gamma increase and later (180–230 ms) gamma suppression. Finally, the ITC was significantly lower in patients in the alpha band, from 30 to 260 ms. Our findings support the putative role of impaired GABA-receptor mediated inhibition in schizophrenia impacting excitatory neurotransmission. Further studies can usefully elucidate mechanisms underlying specific symptoms clusters using TMS-EEG biometrics. • Transcranial magnetic stimulation (TMS) revealed cortical inhibition deficit in schizophrenia. • This tool has recently been combined with electroencephalography (TMS-EEG). • TMS-EEG may shed more light into the pathophysiology of schizophrenia. • TMS-EEG biometrics showed altered excitation/inhibition balance in schizophrenia. • TMS-EEG fingerprints may provide a marker of diagnosis and treatment response. [ABSTRACT FROM AUTHOR]

The article focuses on a case of obsessive-compulsive disorder (OCD) in a patient with a craniopharyngioma, detailing the emergence and persistence of OCD symptoms following neurosurgical intervention. Topics include the association between brain tumors and neuropsychiatric symptoms, the potential impact of tumor location and size on symptom manifestation, and the challenges in managing OCD symptoms in the context of tumor recurrence.

Gynura procumbens (Lour.) Merr., utilized in traditional Chinese medicine, is known for its liver-protective, liver-soothing, and depression-alleviating properties. This research examines the antidepressant and anti-hyperprolactinemia potentials of an ethanol extract from G. procumbens stems (EEGS) and specific metabolites. To model depression and hyperprolactinemia, chronic unpredictable mild stress (CUMS) was induced in mice and risperidone was administered to rats, respectively. Treatments involved administering low (5 mg/kg), medium (25 mg/kg), and high (125 mg/kg) doses of EEGS and certain metabolites to both models. Behavioral assessments were conducted in the CUMS-induced mice, while the CA3 neuronal damage in mice and histopathological alterations in rat mammary glands were evaluated using Nissl and Hematoxylin & Eosin staining techniques, respectively. EEGS decreased immobility times in the forced swimming and tail suspension tests in mice, enhancing their exploration of the central zone. It elevated the serum levels of 5-hydroxytryptamine, norepinephrine, estradiol, luteinizing hormone (LH), and testosterone in mice. Moreover, EEGS restored the neuronal cell arrangement in the CA3 area, reduced interleukin-1beta mRNA production, and increased the expression of interleukin-10 and beta-catenin mRNA. In the context of risperidone-induced hyperprolactinemia, EEGS lowered blood prolactin levels, reduced the dimensions of rat nipples, and enhanced LH, progesterone, and dopamine levels, alongside mitigating mammary hyperplasia. Among the EEGS selected metabolites, the combined effect of chlorogenic acid and trans- p -coumaric acid was found to be more effective than the action of each compound in isolation. Collectively, the findings indicate that EEGS and its selected metabolites offer promising antidepressant benefits while counteracting hyperprolactinemia. [Display omitted] • The ethanol extract of Gynura procumbens stems (EEGS) has anti-depression effect. • EEGS can ameliorate risperidone-induced hyperprolactinaemia. • CA together with t- p -CA from EEGS, has the above-mentioned effects. [ABSTRACT FROM AUTHOR]

• The concomitant polymorphism phenomenon of risperidone in ethyl acetate was investigated. • The nucleation tendencies of form I and form II were analyzed from thermodynamic and kinetic perspectives. • The reasons behind the concomitant polymorphism phenomenon was elucidated based on nucleation parameters of form I and form II. • The occurrence of concomitant polymorphism during slow-cooling crystallization process was discussed. Concomitant polymorphism is a widespread occurrence in industrial crystallization processes. A thorough understanding of this phenomenon is essential to prevent the emergence of undesirable polymorphs and ensure the production of high-quality products. In this study, the induction time method was employed to investigate the concomitant polymorphism phenomenon of risperidone in ethyl acetate. The impact of crystallization temperature and stirring rate on the concomitant polymorphism region was explored. Additionally, an analysis of the nucleation tendencies of risperidone form I and form II was conducted from both thermodynamic and kinetic perspectives. Based on the induction time theory, the nucleation parameters of form I and form II were calculated. Through an examination of the change in these nucleation parameters with supersaturation, a comprehensive explanation was provided for the reasons behind the occurrence of concomitant polymorphism and the nucleation behavior of form I and form II under varying degrees of supersaturation. Moreover, the concomitant polymorphism phenomenon during the slow-cooling crystallization process was investigated, and the relationship between operational conditions and the concomitant polymorphism region was discussed. [ABSTRACT FROM AUTHOR]

By meta-analysing pooled studies and available individual participant data, we aim to provide new insight on olanzapine therapeutic drug monitoring in schizophrenia. We conducted a computerized search of bibliographic databases (Pubmed, Cochrane library, Web of Science and PsycINFO) to identify studies that assessed the relationship between olanzapine plasma concentration and the change in patients' clinical scores. We investigated this relationship with olanzapine plasma level 12h00 post-intake using a random-effects model. 7 studies were included in the pooled data analysis (781 patients). We found no difference in oral dose between responders and non-responders but a significantly higher concentration of 4.50 µg/L in responders (p < 0.01). Olanzapine concentration above the thresholds identified in each study was associated with response (odd ratio = 3.50, p = 0.0007). We identified that non-responder patients showed greater inter-individual variability than responders. In the individual data analysis (159 patients), we found no relationship between dose and clinical response but an association between plasma level and response in the shape of a parabolic curve. The Receiver Operating Characteristic curve found a threshold of 22.07 µg/L to identify responders (96% sensitivity, 86% specificity) and a threshold of 56.47 µg/L to identify a decreased probability of response. In contrast to oral dose, our work confirmed that plasma olanzapine levels are associated with clinical response and should therefore be used to optimise treatment. We determined a treatment response threshold of 22.07 µg/L and suggest that a concentration above the therapeutic window may result in a decreased response. [Display omitted] [ABSTRACT FROM AUTHOR]

Phosphodiesterase 2 A (PDE2A) is an enzyme involved in the homeostasis of cAMP and cGMP and is the most highly expressed PDE in human brain regions critical for socio-cognitive behavior. In cerebral cortex and hippocampus, PDE2A expression level is upregulated in Fmr1 -KO mice, a model of the Fragile X Syndrome (FXS), the most common form of inherited intellectual disability (ID) and autism spectrum disorder (ASD). Indeed, PDE2A translation is negatively modulated by FMRP, whose functional absence causes FXS. While the pharmacological inhibition of PDE2A has been associated to its pro-cognitive role in normal animals and in models of ID and ASD, homozygous PDE2A mutations have been identified in patients affected by ID, ASD and epilepsy. To clarify this apparent paradox about the role of PDE2A in brain development, we characterized here Pde2a +/− mice (homozygote animals being not viable) at the behavioral, cellular, molecular and electrophysiological levels. Pde2a +/− females display a milder form of the disorder with reduced cognitive performance in adulthood, conversely males show severe socio-cognitive deficits throughout their life. In males, these phenotypes are associated with microglia activation, elevated glutathione levels and increased externalization of Glutamate receptor (GluR1) in CA1, producing reduced mGluR-dependent Long-term Depression. Overall, our results reveal molecular targets of the PDE2A-dependent pathway underlying socio-cognitive performance. These results clarify the mechanism of action of pro-cognitive drugs based on PDE2A inactivation, which have been shown to be promising therapeutic approaches for Alzheimer's disease, schizophrenia, FXS as well as other forms of ASD. • Sex-dependent phenotype of Pde2a +/− mice in social discrimination and social interaction • Cognitive deficit in male and female Pde2a +/− mice revealed by the novel object recognition task • -In Pde2a+/ mouse cerebral cortex, an increased number of IBA1+ cells correlates with a reduced number of dendritic spines • mGluR-dependent LTD is reduced in Pde2a +/ CA1 and correlates with an increased phosphorylation level of GluR1 [ABSTRACT FROM AUTHOR]