Positive And Negative Syndrome Scale Total Score Research Articles

Comparing two transitioning strategies to paliperidone palmitate once-every-6-months.

A double-blind, randomized, active-controlled, parallel-group, noninferiority trial (NCT03345342) demonstrated that paliperidone palmitate once-every-6-months (PP6M) was noninferior to paliperidone palmitate once-every-3-months (PP3M) in preventing relapse in clinically stable adults with schizophrenia. This post hoc analysis assessed efficacy and safety following transition to PP6M from paliperidone once-monthly (PP1M) versus PP3M. Adults with schizophrenia who were clinically stable on moderate/high doses of PP1M or PP3M were randomly assigned 1:2 to dorsogluteal PP3M or PP6M treatment for 12months. The primary efficacy measure was time to relapse during the 12-month DB phase. Secondary endpoints included change from DB baseline to endpoint in Positive and Negative Syndrome Scale (PANSS) total and subscale scores, Clinical Global Impression-Severity (CGI-S) scale score, and Personal and Social Performance (PSP) scale score. Safety was assessed by treatment-emergent adverse events (TEAEs), vital signs, and clinical laboratory tests. Of 702 patients in the study, 231 transitioned from PP1M to PP6M and 247 transitioned from PP3M to PP6M. Low relapse rates for PP6M were observed regardless of transition pathway (PP1M/PP6M: 7.8%; PP3M/PP6M: 7.3%). Changes from DB baseline to endpoint in PANSS total, PSP, and CGI-S scores were similar between transition groups. In the DB phase, ≥1 TEAE was observed in 61.0% and 63.2% of patients in the PP1M/PP6M and PP3M/PP6M, groups, respectively. Adults with schizophrenia who transitioned to PP6M from either PP1M or PP3M experienced similarly low relapse rates. Additionally, symptom and functionality scores supported the primary analysis and, along with TEAE incidences, were comparable between transition groups.

Efficacy of xanomeline and trospium chloride in schizophrenia: pooled results from three 5-week, randomized, double-blind, placebo-controlled, EMERGENT trials

In the 5-week, randomized, double-blind, placebo-controlled EMERGENT-1 (NCT03697252), EMERGENT-2 (NCT04659161), and EMERGENT-3 (NCT04738123) trials, xanomeline and trospium chloride (formerly known as KarXT) significantly improved symptoms of schizophrenia and was generally well tolerated. We pooled data from the EMERGENT trials to further characterize the efficacy of xanomeline/trospium and provide sufficient statistical power to analyze responses in participant subgroups. In pooled analyses, xanomeline/trospium significantly improved Positive and Negative Syndrome Scale (PANSS) total score at week 5 versus placebo (least squares mean difference, –9.9; 95% confidence interval, –12.4, –7.3; p < 0.0001; Cohen’s d effect size, 0.65). PANSS subscale and Clinical Global Impression–Severity scores also improved significantly with xanomeline/trospium versus placebo. Subgroup analyses consistently favored xanomeline/trospium over placebo regardless of differences in participant age, sex, race, body mass index, and baseline PANSS total score. These results add to existing evidence demonstrating robust and reliable improvements in symptoms with xanomeline/trospium across a broad spectrum of people with schizophrenia.

Serum IL-6 as a Potential Biomarker of Metabolic Status in Schizophrenia Patients and Its Correlation with Psychotic Symptoms

Objectives: This study aimed to investigate the serum IL-6 level in schizophrenia patients, considering disease chronicity and metabolic status, and to examine its correlation with psychotic symptom scores. The present study also evaluated the diagnostic value of serum IL-6 as a peripheral biomarker for assessing the metabolic health of schizophrenia patients. Methods: Serum IL-6 levels were measured using enzyme-linked immunosorbent assay (ELISA) in 92 schizophrenia patients [44 First Episode Drug Naive (FEDN), 48 chronic schizophrenia (CSZ) patients] and 32 healthy controls. Patients were also stratified into high-risk and no-risk cohorts based on their metabolic status. Psychotic symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Findings: Serum IL-6 levels were significantly higher in schizophrenia patients compared to healthy controls (p&lt;0.001), with no difference between FEDN and CSZ patients (p=0.475). Elevated IL-6 levels were observed in patients in high-risk group compared to those in no-risk group (p&lt;0.001). There was a positive correlation between serum IL-6 levels and BMI (r=0.557, p&lt;0.001), G score (r=0.244, p=0.01), and total PANSS score (r=0.228, p=0.02). Similar associations were found in CSZ patients. The ROC curve analysis showed that serum IL-6 has strong diagnostic potential for distinguishing schizophrenia patients in the high-risk group from those in the no-risk group (AUC=0.875, 95% CI: 0.781-0.969, p&lt;0.001), suggesting its value as a biomarker. Novelty: This study highlights the stable role of serum IL-6 in schizophrenia patients regardless of disease chronicity. The findings suggest that serum IL-6 levels were significantly associated with disease severity as measured by PANSS and metabolic health of schizophrenia patients, providing new insights into its prognostic and diagnostic utility. Early identification and targeted management of high-risk groups can improve patient outcomes and quality of life. Keywords: Schizophrenia, IL-6, FEDN, Chronic, PANSS, Metabolic status, Biomarker

Sex-specific associations between 10-year cardiovascular risk, clinical symptoms and cognitive impairments in schizophrenia.

Schizophrenia (SCZ) shortens life expectancy, with cardiovascular disease (CVD) as the leading cause of death. The links between psychiatric symptoms, cognitive function and CVD are unclear, and sex differences in this relationship are understudied. This study examined the relationship between clinical characteristics and 10-year cardiovascular risk in males and females with SCZ. This study included 802 patients with chronic SCZ. Fasting venous blood samples were collected from all patients to measure relevant glycolipid metabolic indices. The Positive and Negative Syndrome Scale (PANSS) was used to assess psychiatric symptoms. Cognitive function was evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The Framingham risk score (FRS) was used to estimate the 10-year CVD risk. The mean 10-year cardiovascular risk for all patients was 11.76 ± 8.99%. Among patients with SCZ, 52.8% exhibited an intermediate-high 10-year cardiovascular risk. Multivariate linear regression analysis showed that FRS increased with higher body mass index, blood pressure, glucose, total cholesterol and triglyceride levels, while it was inversely related to high density lipoprotein levels. The general psychopathological scores were negatively associated with FRS (male: B = -0.086, P = 0.013; female: B = -0.056, P = 0.039). Negative symptom (B = -0.088, P = 0.024) and total PANSS scores (B = -0.042, P = 0.013) showed a negative association with FRS only in males. Additionally, in patients over 60years old, general psychopathology (B = -0.168, P = 0.001) and PANSS total scores (B = -0.057, P = 0.041) were associated with reduced FRS, while immediate memory (B = 0.073, P = 0.025) was associated with higher FRS. Patients with SCZ have an elevated risk of developing CVD, with males showing a higher 10-year cardiovascular risk than females. Significant sex differences exist in the relationship between the FRS and psychiatric symptoms, with negative symptoms being negatively related to FRS only in males.

Protocol for Cancloz: multicentre randomised, placebo-controlled, double-blind, parallel-group adaptive trial of cannabidiol for clozapine-resistant schizophrenia.

Although clozapine is the most effective antipsychotic for people with treatment-resistant schizophrenia (TRS), only 40% of people with TRS respond, and there is limited evidence for augmentation agents. Cannabidiol (CBD) reduces positive symptoms in individuals with schizophrenia, but no trials have specifically examined its efficacy in those with clozapine-resistant schizophrenia. To examine the clinical efficacy of CBD augmentation in people with clozapine-resistant schizophrenia. This is a 12-week randomised, placebo-controlled, double-blind, parallel-group trial (registration number: ACTRN12622001112752). We will recruit 88 individuals with clozapine-resistant schizophrenia, randomised (1:1) to 1000 mg daily CBD versus placebo. Eligible individuals will be aged between 18 and 64 years, fulfil DSM-IV criteria for schizophrenia or schizoaffective disorder, have a total PANSS (Positive and Negative Syndrome Scale) score ≥60, have received oral clozapine for at least 18 weeks and have a clozapine level of >350 ng/mL. Interim analyses will be conducted at 25, 50 and 75% recruitment; these will also provide an opportunity to reallocate participants dependent on conditional power. The primary endpoint will be the difference in PANSS positive scores at the end of week 12. Secondary endpoints include depression, anxiety, sleep, quality of life, alcohol consumption, change in weight and metabolic syndrome components, and neurocognitive measures, as well as safety and tolerability. Novel treatments for clozapine-resistant schizophrenia are urgently needed. If found to be effective, CBD may have a role as a novel and safe adjunct to clozapine.

Randomized open-label study of second-generation antipsychotics for the treatment of schizophrenia: 104-week final results of the JUMPs study assessing treatment discontinuation, remission, and social functioning

BackgroundWe report the final results of treatment with aripiprazole, blonanserin, and paliperidone from the Japan Useful Medication Program for Schizophrenia (JUMPs), a 104-week naturalistic study.MethodsJUMPs was an open-label, three-arm, randomized, parallel-group, 104-week study. Patients aged ≥ 20 years with schizophrenia requiring antipsychotic treatment or a switch from previous therapy were enrolled. The primary endpoint was treatment discontinuation rate over 104 weeks. Secondary endpoints included remission rate, Personal and Social Performance (PSP), safety, Positive and Negative Syndrome Scale (PANSS), and quality of life (QOL; EuroQol-5 dimension).ResultsIn total, 251 patients received aripiprazole (n = 82), blonanserin (n = 85), or paliperidone (n = 84). Treatment discontinuation rates (aripiprazole, 80.5%; blonanserin, 81.2%; paliperidone, 71.4%) were not significantly different (p = 0.2385) among the treatment groups at 104 weeks; comparable outcomes were observed for endpoints, including remission (42.9%, 46.7%, and 45.8%), PANSS, and safety. In the overall cohort, while the improvement in the PSP total score at Week 104 was not significantly different from baseline, a significant improvement (p < 0.05) in QOL and total PANSS scores (including all subscales) was observed at Week 104 compared with baseline. Multivariable analysis identified a shorter disease duration and a higher chlorpromazine-equivalent antipsychotic dosage level (≥ 1000 mg) before switching to monotherapy as predictors of treatment discontinuation.ConclusionsThe 104-week treatment outcomes were comparable between groups; the overall trend of improvement in remission rate, safety, and QOL suggests the importance of continued treatment.Clinical trial registrationUMIN-Clinical Trials Registry UMIN000007942 (public release date: 14/05/2012).

The potential predictive value and relationship of blood-based inflammatory markers with the clinical symptoms of Han Chinese patients with first-episode adolescent-onset schizophrenia.

Inflammation is associated with the pathophysiology of schizophrenia. The blood markers for systemic inflammation include neutrophil-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), lymphocyte-monocyte ratio (LMR), system inflammation response index (SIRI), and platelet-lymphocyte ratio (PLR). However, these inflammation markers and their relationships with clinical phenotypes among Han Chinese patients with first-episode adolescent-onset schizophrenia (AOS) is unclear. This investigation aimed to elucidate the impact of inflammation on Han Chinese AOS patients as well as the association of blood-based inflammation markers with clinical symptoms. Altogether, 203 Han Chinese individuals participated in this study, 102 first-episode AOS patients and 101 healthy controls. The assessment of inflammatory indices was based on complete blood cell count. Furthermore, schizophrenia-related clinical symptoms were evaluated using the five-factor model of the Positive and Negative Syndrome Scale (PANSS). In Han Chinese first-episode AOS patients, levels of SIRI, PLR, SII, and NLR were significantly increased (p < 0.001), while LMR decreased (p < 0.001) compared to healthy controls. Furthermore, multivariate logistic regression showed that LMR, NLR, SII, and SIRI (all p < 0.05) were independently associated with AOS. Moreover, Receiver operating characteristics assessment indicated that NLR, SIRI, LMR, and SII could effectively distinguish AOS patients from healthy controls. Their areas under the curves were 0.734, 0.701, 0.715, and 0.730 (all p < 0.001). In addition, Correlation analysis revealed that LMR was negatively correlated with the PANSS total, negative, and cognitive factor scores (all p < 0.05); NLR was positively correlated with the cognitive factor score (p < 0.01); SII was negatively correlated with the positive factor score and positively with the negative and cognitive factor scores (all p < 0.05); SIRI was positively correlated with the PANSS total and cognitive factor scores (all p < 0.01). This research established the involvement of peripheral blood inflammatory markers (LMR, NLR, SII, and SIRI) with the clinical manifestations and pathophysiology of schizophrenia, and these can serve as screening tools or potential indices of the inflammatory state and AOS symptoms severity.

Use of video-recordings of site-based interviews for quality assurance in a study of subjects with schizophrenia and persistent negative symptoms

Site-independent ratings derived from audio-digital recordings of site-based interviews are often used for quality assurance monitoring to affirm ratings reliability in CNS clinical trials. The present study of subjects with schizophrenia and persistent negative symptoms used video instead of audio recordings of site-based interviews and thereby facilitated visual observation of the subject by the remote rater. “Paired” site-independent scores of the Positive and Negative Syndrome Scale (PANSS) and Brief Negative Symptom Scale (BNSS) were obtained from video-recordings of site-based interviews.The intraclass correlation between site-based and paired site-independent ratings was r = 0.839 for the total PANSS scores (n = 1006) and r = 0.871 for the total BNSS scores (n = 892); <5 % of paired scores deviated outside the acceptable confidence intervals. Ratings “outliers” were identified and remediated.We examined the pattern of paired scoring deviations for the BNSS, total PANSS, PANSS symptom subscales, and the Marder negative symptom factor. Each metric revealed a bidirectional pattern of scoring deviations such that mean site-based ratings were higher than site-independent ratings when symptom severity was high but lower than site-independent ratings when symptom severity was low.The pattern of bidirectional paired scoring deviations observed in this analysis has previously been noted in paired ratings analyses of subjects experiencing an acute exacerbation of psychosis in schizophrenia and major depressive disorder as well. The bidirectional pattern may reflect inherent differences between live ratings and remotely scored recorded ratings.This analysis affirms the utility of video-recordings of site-based ratings for surveillance in trials with subjects with schizophrenia and persistent negative symptoms.

Evaluation of Clinical Correlation between Insulin Resistance and Antipsychotic Drug Therapy in Patients with Schizophrenia.

Treatment with different antipsychotics can lead to various metabolic side effects in patients with psychosis, impacting long-term prognosis. This study aimed to compare the changes and clinical efficacy of insulin resistance in patients treated with olanzapine and ziprasidone. A retrospective analysis was conducted on the clinical data of 80 patients with schizophrenia. The patients were divided into olanzapine treatment group and ziprasidone treatment group. Parameters including body weight, body mass index (BMI), fasting plasma glucose (FPG), fasting plasma insulin (FPI), cholesterol (CHO), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), insulin resistance index, and Positive and Negative Syndrome Scale (PANSS) scores were recorded and compared before and after treatment. BMI, FPG, FPI, homeostatic model assessment of insulin resistance (HOMA-IR), CHO, TG and LDL in both groups were significantly higher than before treatment (p < 0.05). These parameters were significantly higher in the olanzapine group than in the ziprasidone group (p < 0.05). The level of HDL in both groups was significantly decreased after treatment, and the level of HDL in the olanzapine group was significantly lower than that in the ziprasidone group after treatment (p < 0.05). After treatment, the total score and score of PANSS in both groups were significantly lower than before treatment (p < 0.05). After treatment, there was no significant difference in total score and PANSS score between both groups (p > 0.05). The incidence of insulin resistance (IR) was significantly higher in the olanzapine group compared to the ziprasidone group (χ2 = 4.021, p < 0.05). In the IR group, BMI, FPG, FPI, TG, and LDL levels were higher than in the non-IR group (p < 0.05). Multivariate analysis indicated that BMI, FPG, FPI, TG, and LDL were independent risk factors for IR (odd ratio (OR) >1, p < 0.05). Treatment with olanzapine and ziprasidone improves clinical symptoms in patients with schizophrenia, but increases the risk of insulin resistance. The metabolic side effects of olanzapine are more pronounced.

Plasma G72 protein in schizophrenia: A comparative analysis of drug-naive schizophrenia patients, patients in acute exacerbation and healthy controls

ObjectivesSchizophrenia is a complex psychiatric disorder with an unclear etiopathogenesis. This study investigates the plasma G72 protein levels in drug-naive schizophrenia patients (DNS), those in acute psychotic episodes (AES), and healthy controls (HC). It also examines the correlation between the plasma G72 protein levels and Positive and Negative Syndrome Scale (PANSS) scores. MethodsThe study included 138 schizophrenia patients (84 DNS, 54 AES) and 83 HCs. Plasma G72 protein levels were measured by ELISA. Statistical analyses, including log-transformation and correlation analysis, were conducted. ResultsSchizophrenia patients had significantly lower plasma G72 levels than HCs (4.39 ± 5.38 vs. 8.06 ± 10.27 ng/mL, p < 0.001), while DNS and AES groups did not differ significantly. Log-transformed data confirmed these differences. Negative correlation was found between plasma G72 levels and age (r = −0.258, p = 0.02), PANSS-G (r = −0.249, p = 0.004), and total PANSS scores (r = −0.226, p = 0.008). ROC analysis showed poor discrimination between schizophrenia patients and controls (AUC: 0.587, p = 0.031). ConclusionsThis study's novel findings reveal that plasma G72 protein levels are significantly lower in schizophrenia patients and inversely correlated with age and symptom severity. However, the poor diagnostic accuracy observed in the ROC analysis suggests that G72 may not be a reliable biomarker for schizophrenia at this stage. These results underscore the need for further research to explore the potential clinical implications of these findings.

Efficacy and Safety of Lurasidone vs. Quetiapine XR in Acutely Psychotic Patients With Schizophrenia in Korea: A Randomized, Double-Blind, Active-Controlled Trial.

This study was performed to evaluate the efficacy and safety of lurasidone (160 mg/day) compared to quetiapine XR (QXR; 600 mg/day) in the treatment of acutely psychotic patients with schizophrenia. Patients were randomly assigned to 6 weeks of double-blind treatment with lurasidone 160 mg/day (n=105) or QXR 600 mg/day (n=105). Primary efficacy measure was the change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impressions severity (CGI-S) score. Adverse events, body measurements, and laboratory parameters were assessed. Lurasidone demonstrated non-inferiority to QXR on the PANSS total score. Adjusted mean±standard error change at week 6 on the PANSS total score was -26.42±2.02 and -27.33±2.01 in the lurasidone and QXR group, respectively. The mean difference score was -0.91 (95% confidence interval -6.35-4.53). The lurasidone group showed a greater reduction in PANSS total and negative subscale on week 1 and a greater reduction in end-point CGI-S score compared to the QXR group. Body weight, body mass index, and waist circumference in the lurasidone group were reduced, with significantly lower mean change compared to QXR. Endpoint changes in glucose, cholesterol, triglycerides, and low-density lipoprotein levels were also significantly lower. The most common adverse drug reactions with lurasidone were akathisia and nausea. Lurasidone 160 mg/day was found to be non-inferior to QXR 600 mg/day in the treatment of schizophrenia with comparable efficacy and tolerability. Adverse effects of lurasidone were generally tolerable, and beneficial effects on metabolic parameters can be expected.

Long-term safety and effectiveness of lurasidone in adolescents and young adults with schizophrenia: pooled post hoc analyses of two 12-month extension studies

Background and ObjectivesThe aim of this analysis was to evaluate the long-term safety and effectiveness of lurasidone in the treatment of schizophrenia in adolescents and young adults (13–25).MethodsThe 2 pooled studies used similar designs and outcome measures. Patients (13–25) with schizophrenia completed an initial double-blind 6-week trial of lurasidone (40 and 80 mg/day) in the adolescent trial and (80 and 160 mg/day) in the young adult trial. In open-label long-term trials, adolescent patients were treated with 20–80 mg/day lurasidone, and adults were treated with 40–160 mg/day lurasidone. Efficacy was evaluated based on the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Severity Scale (CGI-S).ResultsThe safety population consisted of 306 patients (mean age, 16.2 years; 208 patients (68.0%) who completed 12 months of treatment; 8.2% who discontinued treatment by 12 months due to an adverse event). The mean (SD) changes in the PANSS total score from the extension baseline to months 6 and 12 were − 11.8 (13.9) and – 15.3 (15.0), respectively (OC), and the mean (SD) changes in the CGI-S score were − 0.8 (1.0) and − 1.0 (1.1), respectively (OC). The most frequent adverse events were headache (17.6%), anxiety (11.4%), schizophrenia (9.8%), and nausea (9.8%). No clinically meaningful changes were observed in weight, metabolic parameters, or prolactin.ConclusionsIn adolescents and young adults with schizophrenia, treatment with lurasidone was generally well tolerated and effective. Long-term treatment was associated with a continued reduction in symptoms of schizophrenia. Long-term treatment was associated with minimal effects on weight, metabolic parameters, and prolactin.Clinicaltrials.gov identifiers D1050234, D1050302.

Transcranial direct current stimulation improves tardive dyskinesia in long-term hospitalized patients with chronic schizophrenia

ObjectiveThis study aimed to evaluate the efficacy and safety of transcranial direct current stimulation (tDCS) in chronic schizophrenia patients with tardive dyskinesia (TD) who were long-term hospitalized. MethodsSixty-four inpatients who met the DSM-IV diagnostic criteria for schizophrenia and TD were randomly assigned to either the active (N=35) or sham (N=29) group. Treatment was given 15 times, with each session lasting for 30 min, and an intensity of 2 mA. The anode was placed on the left dorsolateral prefrontal cortex and the cathode on the right supraorbital region. Primary outcome was measured by the changes in Abnormal Involuntary Movements Scale (AIMS) score. Secondary outcomes were measured using the Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS). Adverse effects of tDCS were assessed with an experimenter-administered open-ended questionnaire throughout the experiment. ResultsOf the 64 patients, 52 (81.25%) completed the study. Compared to the sham group, patients in the active group exhibited a significant reduction in both the total AIMS score and the facial-oral subscore (P<0.05). An improvement of at least 30% in total AIMS scores was observed in the active group (14 patients, 50%) compared to the sham group (2 patients, 8.3%) after treatment (P<0.01). There were no between-group differences in the PANSS and SANS total scores. However, there was a significant difference between the two groups in the occurrence of the reported adverse effect of tingling sensation (P<0.05). ConclusionsTDCS may be an effective and safe treatment for improving the facial-oral motor symptoms of TD in chronically hospitalized patients with schizophrenia. SignificanceThis study provides a novel perspective for the clinical treatment of patients with TD.

Correlation Between Severity of Schizophrenia with Certain Trace Elements and TNF-α Gene Expression and Its Circulatory Level in the Population of Western India.

This cross-sectional study aimed to assess serum trace element (TE) concentrations, TNF-α gene expression, protein levels in schizophrenia (SZ) patients, and their correlation with disease severity measured by Positive and Negative Syndrome Scale (PANSS) scores. Forty SZ cases and 40 healthy controls aged 18-60 were recruited. Forty (n = 40) cases who meet ICD-10 criteria for SZ and 40 (n = 40) healthy individuals (controls) between 18 and 60years of age were recruited in the study. Sandwich enzyme-linked immunosorbent assay (ELISA) and RT-qPCR (quantitative real-time PCR) were used to estimate pro-inflammatory cytokine TNF-α protein and gene expression. Inductively coupled plasma-optical emission spectroscopy (ICP-OES) and graphite furnace atomic absorption spectroscopy (GFAAS) were used to assess serum levels of trace elements (TEs): Fe, Zn, Cu, Mg, and Se. Compared to healthy controls, cases had significantly higher levels of TNF-α protein, as well as Fe, Cu, and Se (p < 0.05). Cu correlated positively with TNF-α protein level (rho = 0.234; p = 0.048) and gene expression (rho = 0.333; p = 0.041) and with PANSS negative (rho = 0.531), general (rho = 0.643), and total (rho = 0.541) scores. Additionally, Zn negatively correlated with serum Mg (rho = - 0.426, p < 0.01) and positively with serum Se (rho = 0.343, p < 0.05). In conclusion, elevated Cu levels could potentially contribute to the development of SZ. Elevated Cu levels in cases and their correlation with the TNF-α gene and protein and PANSS score indicate Cu's potential role in exacerbating SZ severity through inflammatory cytokines. This suggests the involvement of metals and cytokines in the pathophysiology of SZ.

Cariprazine in the management of emotionally unstable personality disorder in female patients: a case series.

Emotionally unstable personality disorder (EUPD) is debilitating psychiatric disorder, particularly common in female and forensic populations. However, appropriate pharmacological treatment to effectively manage symptoms of EUPD remains an unmet clinical need. Dopamine receptor partial agonists (DRPAs), such as aripiprazole, have a favourable tolerability profile and have demonstrated some benefits in targeting symptoms of emotional dysregulation, although, evidence regarding the effects of novel D2/D3 DRPA cariprazine in EUPD patients has been limited. To evaluate the efficacy and tolerability of cariprazine for EUPD in a case series of female forensic inpatients where the diagnosis is more prevalent. Demographic and clinical information of the patients were collected from patient electronic records during their admission in a specialized NHS forensic service. Treatment response was measured using the Positive and Negative Syndrome Scale (PANSS) at baseline, 3 and 6 months and Global Clinical Impression Scale (CGI-scores) at baseline and 6 months. Tolerability and BMI, ECG QTc interval and prolactin levels were recorded prior to initiation and at 6 months. Eight female patients with EUPD (mean age 29.8 years, SD 5.3) were treated with cariprazine (range 3-6mg). Total CGI-scores modestly improved from 5.6 baseline to 5.0 at 6 months. There was a reduction in mean total PANSS scores from baseline to 6 months (92.5, SD 8.1 to 72.4, SD 15.8), general psychopathology (56.1 SD 6.7 to 42.5, SD9.7), positive (21.9 SD 4.6 to 17.1, SD4.8) and negative PANSS scores (14.5 SD 6.3 to 12.8, SD4.6), corresponding to a 21%, 23%, 20% and 3% mean score reduction, respectively. Cariprazine demonstrated a favourable metabolic and hormonal side effect profile with no treatment discontinuation at 6 months follow up. This is the first case series to evaluate the effectiveness of cariprazine in EUPD. Its efficacy in improving PANSS and CGI-S scores was overall modest and highly variable, reflective of an inherently heterogenous and comorbid patient sample but the benefits on treatment perseverance and tolerability were considerable. Cariprazine may be of particular benefit in EUPD where psychotic symptoms are co-morbid, as an augmentation strategy to clozapine, or where previous antipsychotics have caused metabolic or hormonal side effects.

White matter microstructure alterations of the posterior limb of internal capsule in first-episode drug naive schizophrenia patients

ObjectivesPrevious studies have shown that microstructural alterations in white matter (WM) could contribute to the symptom manifestation and support the dysconnectivity hypothesis in schizophrenia patients. These alterations were pervasive, non-specific, and reported inconsistently across the literature. This study aimed to specifically investigate the microstructure alterations of the posterior limb of the internal capsule (PLIC) in first-episode, drug-naive schizophrenia patients. Utilizing a multicompartmental biophysical model, we further explored the correlation between these alterations and syndrome scale scores. MethodsThirty-two individuals with first-episode, drug-naive schizophrenia (FES) and thirty demographically matched healthy controls were enrolled. High-resolution multi-shell diffusion MRI data were collected, followed by the application of a three-compartment Neurite Orientation Dispersion and Density Imaging (NODDI) model to scrutinize the alterations in white matter microstructure. Changes in sensory and motor fibers within the PLIC were specifically focused on. Additionally, the correlation between these pathological changes and scores on the Positive and Negative Syndrome Scale (PANSS) was investigated. ResultsThe Neurite density index (NDI) in the left PLIC was significantly lower in FES patients compared to healthy individuals, and positively correlated with PANSS positive syndrome scores (r = 0.0379, p = 0.046). In the sensory component (left superior thalamic radiation within PLIC, STR_P), the NDI was significantly elevated (p < 0.0001). Conversely, the NDI in the motor component (left corticospinal tract within PLIC, CST_P) was reduced (p = 0.007) in FES patients compared to healthy individuals, and strongly correlated with PANSS positive syndrome scores (p < 0.020) and PANSS total scores (p < 0.045). Moreover, the NDI deviation of STR from total PLIC (fSTR_P) and NDI deviation in STR_P and CST_P compared to PLIC region (fPLIC) were significantly higher in FES patients than in healthy controls (p < 0.00001), with an area under the curve (AUC) of fPLIC reaching 0.872. ConclusionThe study’s findings provided new insights into the discrepancy of white matter microstructure changes associated with the sensory and motor fibers in the PLIC region in FES patients. These results contribute to the growing body of evidence suggesting that WM microstructural alterations play a critical role in schizophrenia pathophysiology.

Relationship between plasma TNF-α levels and agitation symptoms in first episode patients with schizophrenia

BackgroundIncreasing evidence suggested that immune abnormalities involved in the pathophysiology of schizophrenia. However, the relationship between immunity and clinical features has not been clarified. The aim of this study was to measure the plasma levels of tumor necrosis factor alpha (TNF-α) and soluble TNF-α receptor 1 (sTNF-α R1) and to investigate their association with agitation in first episode patients with schizophrenia (FEPS).MethodsThe plasma TNF-α and sTNF-α R1 levels were measured using sandwich enzyme-linked immunosorbent assay (ELISA) in the FEPS with (n = 36) and without agitation (n = 49) symptoms, and healthy controls (HCs, n = 54). The psychopathology was assessed by the Positive and Negative Syndrome Scale (PANSS), and the agitation symptoms were evaluated by the PANSS excitatory component (PANSS-EC).ResultsThe plasma TNF-α levels in patients with and without agitation symptoms were significantly higher than those in HCs. The patients with agitation had significantly higher plasma TNF-α levels compared to the patients without agitation. There were no significant differences in the sTNF-α R1 levels among the three groups. Furthermore, the plasma TNF-α levels were positively correlated with the PANSS total score, Positive and General psychopathological subscores, and PANSS-EC score in the FEPS, but the relationships were not found for the plasma sTNF-α R1 levels.ConclusionsThese results suggested that TNF-α might play an important role in the onset and development of agitation symptoms of schizophrenia.

Association between Brain-derived Neurotrophic Factor (BDNF) Val66Met polymorphism and Clinical Outcomes as Measured with PANSS Scale in Patients With Schizophrenia in Two Psychiatric Centres in East Java – Indonesia

Aim: The etiology of schizophrenia has been linked to complex interactions of genetic and environmental factors, and among them are genes that regulate BDNF (Brain-derived Neurotrophic Factor) expression. The BDNF has been linked to the pathophysiology of schizophrenia, particularly the Val66Met polymorphism. This study aims to assess BDNF Val66Met polymorphism and its role in positive and negative symptoms in patients with schizophrenia in East Java. Subjects and Methods: A total of 52 subjects with schizophrenia living in East Java were assessed for BDNF Val66Met polymorphism. The analysis was performed using Statistical the Social Sciences (SPSS) software version 22. Clinical assessment was conducted using the positive and negative syndrome scale (PANSS). Data were analyzed using linear regression multivariate analysis. Results: Our study found that Val/Met polymorphism is associated negatively with the total PANSS scores (beta coefficient = -12.299, p = 0.017). The Val/Val polymorphism is associated with negative symptoms (beta coefficient = 22.607, p = 0.043). The present study’s findings considered age, gender, education level, number of antipsychotics consumed, medication adherence, and duration of untreated psychosis. Conclusion: Val/Val polymorphism is associated with a higher PANSS total score. Val/Met genotype is associated with more severe positive symptoms, while the Val/Val genotype is associated with more negative symptoms. Further study with a larger and multicenter sample is needed to clarify further the relationship of BDNF polymorphism to clinical outcomes of schizophrenia.

COMT and Neuregulin 1 Markers for Personalized Treatment of Schizophrenia Spectrum Disorders Treated with Risperidone Monotherapy.

Pharmacogenetic markers are current targets for the personalized treatment of psychosis. Limited data exist on COMT and NRG1 polymorphisms in relation to risperidone treatment. This study focuses on the impact of COMT rs4680 and NRG1 (rs35753505, rs3924999) polymorphisms on risperidone treatment in schizophrenia spectrum disorders (SSDs). This study included 103 subjects with SSD treated with risperidone monotherapy. COMT rs4680, NRG1 rs35753505, and rs3924999 were analyzed by RT-PCR. Participants were evaluated via the Positive and Negative Syndrome Scale (PANSS) after six weeks. Socio-demographic and clinical characteristics were collected. COMT rs4680 genotypes significantly differed in PANSS N scores at admission: AG>AA genotypes (p = 0.03). After six weeks of risperidone, PANSS G improvement was AA>GG (p = 0.05). The PANSS total score was as follows: AA>AG (p = 0.04), AA>GG (p = 0.02). NRG1 rs35753504 genotypes significantly differed across educational levels, with CC>CT (p = 0.02), and regarding the number of episodes, TT>CC, CT>CC (p = 0.01). The PANSS total score after six weeks of treatment showed a better improvement for TT<CT genotypes (p = 0.01). NRG1 rs3924999 genotypes revealed GG<AG (p = 0.02) for PANSS G scores after six weeks, with AG and GG requiring higher doses (p = 0.007, p = 0.02). Overall, our study suggests that the genetic polymorphisms COMT rs4680, NRG1 rs35753505, and rs3924999 significantly impact the treatment response to risperidone in patients with SSD.

Computerized cognitive remediation therapy on cognitive impairment and social function in patients with chronic schizophrenia

BACKGROUND Patients with schizophrenia may have various disease manifestations, most of which gradually tend toward incurable chronic decline, leading to mental disability. The basic symptoms of the disease can impair social function, whereas long-term hospitalization produces hospitalization syndrome, causing serious damage to social function. AIM To investigate the effects of Computerized Cognitive Remediation Therapy (CCRT) on cognitive and social functioning in patients with chronic schizophrenia. METHODS A retrospective analysis of 120 patients with chronic schizophrenia in Shanghai Pudong New Area Mental Health Center was performed. They were divided into an intervention group (60 cases treated with CCRT combined with conventional medication) and a control group (60 cases treated with conventional medication). After treatment, effects on cognitive function and social roles were observed in both groups. The Positive and Negative Syndrome Scale (PANSS) was used to assess the patients' psychiatric symptoms. The Wisconsin Card Sorting Test (WCST) was used to assess the patients' cognitive functioning, and the Social Functioning Scale for Psychiatric Inpatients (SSPI) was used to assess the social functioning of the inpatient psychiatric patients. RESULTS No significant differences were observed in the PANSS, WCST, and SSPI intergroup scores before treatment (P &gt; 0.05). After 2, 4, and 6 wk of therapy, general psychopathological factors, positive symptoms, negative symptoms, and total PANSS scores of PANSS in the intervention group were lower than in the control group (P &lt; 0.05). After 2, 4, and 6 wk of treatment, the number of false responses, number of persistent bugs, and total responses in the WCST were significantly lower in the intervention group than in the control group (P &lt; 0.05), and the amount of completed classification was significantly higher than in the control group (P &lt; 0.05). After 2, 4, and 6 wk of therapy, the SSPI scores were significantly greater than those of the controls (P &lt; 0.05). After 6 wk of treatment, the efficacy rates of the control and intervention groups were 81.67% and 91.67%, respectively. The curative effect in the intervention group was significantly higher than that in the control group (P &lt; 0.05). CONCLUSION CCRT can significantly improve cognitive function and social abilities in patients with chronic schizophrenia.