Positive And Negative Syndrome Scale Subscales Research Articles

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.

Circulating microRNA Profiles Identify a Patient Subgroup with High Inflammation and Severe Symptoms in Schizophrenia Experiencing Acute Psychosis.

Schizophrenia is a complex and heterogenous psychiatric disorder. This study aimed to demonstrate the potential of circulating microRNAs (miRNAs) as a clinical biomarker to stratify schizophrenia patients and to enhance understandings of their heterogenous pathophysiology. We measured levels of 179 miRNA and 378 proteins in plasma samples of schizophrenia patients experiencing acute psychosis and obtained their Positive and Negative Syndrome Scale (PANSS) scores. The plasma miRNA profile revealed three subgroups of schizophrenia patients, where one subgroup tended to have higher scores of all the PANSS subscales compared to the other subgroups. The subgroup with high PANSS scores had four distinctively downregulated miRNAs, which enriched 'Immune Response' according to miRNA set enrichment analysis and were reported to negatively regulate IL-1β, IL-6, and TNFα. The same subgroup had 22 distinctively upregulated proteins, which enriched 'Cytokine-cytokine receptor interaction' according to protein set enrichment analysis, and all the mapped proteins were pro-inflammatory cytokines. Hence, the subgroup is inferred to have comparatively high inflammation within schizophrenia. In conclusion, miRNAs are a potential biomarker that reflects both disease symptoms and molecular pathophysiology, and identify a patient subgroup with high inflammation. These findings provide insights for the precision medicinal strategies for anti-inflammatory treatments in the high-inflammation subgroup of schizophrenia.

Sex-specific associations of plasma neutrophil gelatinase-associated lipocalin (NGAL) with cognition in patients with drug-naïve schizophrenia

This present study aimed to investigate the sex-specific association of plasma neutrophil gelatinase-associated lipocalin (NGAL) with cognition in drug-naïve schizophrenia patients for the first time. A total of 204 participants in this study, including 137 drug-naïve schizophrenia (DNS) patients and 67 healthy controls (HCs). All participants completed the Measurements and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB), and were collected fasting venous blood for NGAL measurement. DNS patients also complete the Positive and Negative Syndrome Scale (PANSS). Partial correlation analysis and multiple linear regression were used to explore sex-specific associations between NGAL and cognition. All dimensions of MCCB scores were significantly lower in both male and female DNS patients than HCs. Sex differences were significant in cognitive performance in both DNS patients and HCs. Female DNS patients experienced poorer working memory and reason& problem solving than male patients. Female HCs performed a better attention/vigilance and visual learning, a poorer reason& problem solving than male HCs. In patients with DNS, NGAL levels were negatively associated with positive subscale of PANSS and positively associated with working memory and visual learning only in female. However, there was no significant correlation between NGAL levels and all cognitive tests in both male and female HCs. Regression model showed that higher level of NGAL was an independent protective factor for cognitive performance in female patients with DNS, whereas there was no such role in male patients. Our findings suggest sex specificity between NGAL levels and cognitive performance in DNS patients.

Insight into Illness Among Inpatients in a National Forensic Mental Health Service: A Dundrum Forensic Redevelopment Evaluation Study (D-FOREST)

IntroductionForensic psychiatric services serve a dual purpose: treatment of mental disorders and prevention of associated violent reoffending. Progression along the secure care pathway is often impeded by impaired insight, mainly as a result of treatment-resistant psychoses.ObjectivesWe assessed levels of insight among patients in Ireland’s National Forensic Mental Health Service before and after its relocation from the historic 1850 campus in Dundrum to a modern facility in Portrane, Dublin.MethodsThe VAGUS insight scale was used in this repeated measures study before and after the relocation at two time points 42 months apart. All inpatients were invited to participate in completing the self-report (VAGUS-SR) and clinician-rated (VAGUS-CR) versions on both occasions. Total scores of both versions were averaged to obtain a combined VAGUS insight score. Corresponding Positive and Negative Syndrome Scale (PANSS) scores were used to ascertain correlations between the insight and symptomatology scales. This study is part of the Dundrum Forensic Redevelopment Evaluation Study (D-FOREST)Results40 pairs of observations were available for legal capacity to consent to medication, combined VAGUS-CR and VAGUS-SR assessments of insight (Cronbach’s alpha=0.927), and PANSS. VAGUS-CR insight and PANSS scores were progressively better from admission and high dependency wards through medium-term medium secure wards to rehabilitation and pre-discharge wards. Mean scores did not change significantly over this time interval. Those legally certified fit to give or withhold consent by their treating consultant psychiatrists scored significantly better on the VAGUS combined insight scale: 8.3 (SD 1.7) v 5.3 (2.2) at baseline, paired t=25.9, p&lt;0.001; and also 42 months later: 8.2 (1.4) v 5.7 (3.9), paired t=5.2, p=0.022. PANSS subscales were all significantly better for those assessed as being capacitous. Change in combined VAGUS score correlated with change in all PANSS subscales. Binary logistic regression with legal capacity as the dependent variable yielded a model in which combined VAGUS score and PANSS positive symptom score were independent determinants of assessed capacity status. Receiver operating characteristic area under the curve was 0.873, 95% CI 0.760-0.986, at baseline and 0.856, 95% CI 0.720-0.991, at 42 months. A score of 7.3 yielded a sensitivity of 0.8 and a specificity of 0.8.ConclusionsThe combined VAGUS score is a reliable and valid measure of insight relevant to functional mental capacity to consent to treatment with sensitivity and specificity sufficient to guide but not bind clinical decision-making. It measures a quality that varies with symptom severity but is also partly independent of symptom severity; the constructive inclusion of self-reported insight is notable.Disclosure of InterestNone Declared

Variations of plasma oxidative stress levels in male patients with chronic schizophrenia. Correlations with psychopathology and matrix metalloproteinase-9: a case-control study

BackgroundAccumulating evidence has indicated that oxidative stress (OS) and matrix metalloproteinase-9 (MMP-9) may contribute to the mechanism of schizophrenia. In the present study, we aimed to evaluate the associations of OS parameters and MMP-9 levels with psychopathological symptoms in male chronic schizophrenia patients.MethodsThis study was an observational, cross-sectional, retrospective case-control study. Plasma hydrogen peroxide (H2O2), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), serum matrix metalloproteinase-9 (MMP-9), and tissue inhibitors of metalloproteinases-1 (TIMP-1) levels were assayed in 80 male patients with chronic schizophrenia and 80 matched healthy controls. Schizophrenia symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS). Multivariate regression was used to analyze relationships between OS parameters and MMP-9, and clinical symptoms.ResultsOur results demonstrated that levels of antioxidant enzymes, SOD, GSH-Px, H2O2, and MDA were significantly decreased, whereas CAT and MMP-9 levels were increased in patients with schizophrenia, when compared with healthy controls (all P < 0.05). In schizophrenia patients, correlation analyses showed that H2O2 levels were significantly and positively correlated with PANSS positive scores, CAT and MDA levels were significant negatively correlated with PANSS negative scores and PANSS total scores, and MDA levels were significantly positively correlated with MMP-9 levels (all P < 0.05). However, we did not find that MMP-9 played an interaction role between OS parameters and PANSS total scores and subscales scores (all P > 0.05).ConclusionsOur results showed that alterations of plasma OS parameters in male patients with chronic schizophrenia were associated with psychopathology and MMP-9, suggesting that OS and neuroinflammation may play important role in the mechanism of schizophrenia.

Cognitive effects of brief and intensive neurofeedback treatment in schizophrenia: a single center pilot study.

Schizophrenia is characterized by significant cognitive impairments and affects up to 98% of patients. Neurofeedback (NF) offers a means to modulate neural network function through cognitive processes such as learning and memorization, with documented structural changes in the brain, most notably an increase in grey matter volume in targeted regions. The present 2-week, open-label, preliminary study aims to evaluate the efficacy on cognition of an adjunctive short and intensive (8 daily sessions lasting 30 minutes) alpha/theta NF training in a sample of subjects affected by schizophrenia on stabilized treatment with atypical antipsychotic drugs. The efficacy was measured at baseline and at the end of the study by the Brief Neuropsychological Examination 2 (ENB 2), the Mini Mental State Examination (MMSE), and the Stroop color-word interference test; the clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). A final sample of nine patients completed the study. Regarding the cognitive performance, at the final assessment (week 2), the NF treatment significantly improved the performance in the "Story Recall Immediate" (p = 0.024), "Story Recall Delayed" (p = 0.007), "Interference Memory 30 s" (p = 0.024), "Clock Test" (p = 0.014) sub-tests, and the ENB2 Total Score (p = 0.007). Concerning the clinical symptoms, no significant changes were observed in the PANSS subscales and the PANSS Total score. NF could represent an adjunctive treatment strategy in the therapeutic toolbox for schizophrenia cognitive symptoms.

Alexithymia is associated with insomnia in Chinese patients with schizophrenia.

Sleep disorders are prevalent among patients with schizophrenia and are associated with several negative consequences. Although, researchers have recently suggested that sleep disorders have a close correlation with alexithymia, and schizophrenia also has a strong correlation with alexithymia, there have been few studies on the relationships between schizophrenia, sleep disorders and alexithymia. Therefore, this study aimed to explore the relationships between psychiatric symptoms, alexithymia and sleep problems in patients with schizophrenia so as to provide a reference for the clinical treatment of this comorbidity. In total, 977 patients with schizophrenia were recruited for this study. The Insomnia Severity Index (ISI) was used to assess sleep disorders, and the Positive and Negative Syndrome Scale (PANSS), Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Toronto Alexithymia Scale (TAS) were used to evaluate clinical symptoms, cognitive functions and the ability to express emotion, respectively. The results indicated that the PANSS subscales (G-subscore) and TAS group were risk factors for insomnia in schizophrenia patients (all p < 0.05). The mediation model showed the standardized path coefficients from schizophrenia to alexithymia (β = 0.104, p < 0.001) and from alexithymia to insomnia (β = 0.038, p < 0.001) were statistically significant. The results of this study indicated that alexithymia is associated with sleep disturbance in patients with schizophrenia. These findings may provide a new avenue for the treatment of schizophrenia patients with sleep disorders.

Clinical correlates and thyroid hormones of metabolic syndrome in first-episode and drug-naïve major depressive disorder outpatients with and without hyperglycemia: a comprehensive cross-sectional study

Hyperglycemia and metabolic syndrome (MetS) are common in patients with major depressive disorder (MDD). This study aimed to explore the prevalence and clinical factors of MetS in first-episode and drug-naïve MDD (FEDND) patients with and without hyperglycemia. A total of 1,718 FEDND patients’ symptoms were assessed using the Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), and positive subscale of the Positive and Negative Syndrome Scale (PANSS). Blood glucose levels, metabolic index, and thyroid hormones were measured during fasting. The prevalence of MetS in FEDND patients with hyperglycemia was 35.67 times higher than in FEDND patients without hyperglycemia. FEDND patients with MetS were older, had later age of onset, and were predominantly married than those without MetS (p < 0.05). Among FEDND patients without hyperglycemia, suicide attempts, severe anxiety, HAMD, HAMA, PANSS subscale scores, thyroid stimulating hormone, antithyroglobulin, and total cholesterol levels were all higher in patients with MetS than those without MetS (all p < 0.05). In FEDND patients without hyperglycemia, the combination of age and TgAb distinguished those patients with and without MetS. Our results suggest a high prevalence of MetS in FEDND patients with hyperglycemia. Several clinical variables and thyroid function-related hormones impact MetS in patients with FEDND.

Initial severity of the Positive and Negative Syndrome Scale (PANSS)-30, its main subscales plus the PANSS-6, and the relationship to subsequent improvement and trial dropout: a pooled participant-level analysis of 18 placebo-controlled risperidone and paliperidone trials

Greater initial severity on the 30-item Positive and Negative Syndrome Scale (PANSS-30) correlates positively with antipsychotic-placebo separation and trial dropout, but it is unknown whether these associations are present also on PANSS-derived subscales. We assessed the relationship between initial severity and antipsychotic-placebo separation as measured by PANSS-30 and four PANSS symptom subscales: the positive (PANSS-POS), negative (PANSS-NEG), general (PANSS-GEN) and 6-item (PANSS-6) subscales, using patient-level data from 18 placebo-controlled risperidone and paliperidone trials. Analysis of covariance in the intention-to-treat population (last-observation-carried-forward) was used to assess antipsychotic-placebo separation and trial dropout. Across 6685 participants (90% schizophrenia, 10% schizoaffective disorder), the initial severity-by-treatment interaction was statistically significant for PANSS-30 (beta: −0.155; p < 0.001) and all PANSS subscales (beta range: −0.097 to −0.135; p-value range: < 0.001 to 0.002). In all cases, antipsychotic-placebo differences increased with initial severity. Judging by the distribution of relative outcomes (percent remaining symptoms), the interaction was partly explained by an increased chance of responding, but also by larger numerical responses in those who did respond, as initial severity increased. Except for PANSS-NEG, high initial severity on all PANSS scales predicted increased trial dropout, although not statistically significantly so for PANSS-6. In summary, we thus replicate previous findings showing greater initial severity to predict larger antipsychotic-placebo separation and extend these results to four PANSS subscales. For PANSS-POS and PANSS-GEN, but not for PANSS-NEG and PANSS-6, we also replicate the association between initial severity and trial dropout. Patients with low initial negative symptom severity were identified as a group of particular interest for further study since their results diverged most from the average both with regard to antipsychotic-placebo separation (low separation measured by PANSS-NEG) and trial dropout (high level).

Impact of Childhood Trauma and Adult Separation Anxiety Disorder on Quality of Life in Individuals with Schizophrenia.

Childhood trauma and anxiety disorders are common in individuals with schizophrenia. This study aimed to investigate the effects of childhood trauma and adult separation anxiety disorder on the quality of life of individuals with schizophrenia. This cross-sectional study included 111 individuals with schizophrenia and 85 control subjects. The separation anxiety symptom inventory (SASI), adult separation anxiety questionnaire (ASAQ), Positive and Negative Syndrome Scale (PANSS), childhood trauma questionnaire (CTQ), and World Health Organization quality of life questionnaire (WHOQoL-BREF) were administered to the participants. More individuals with schizophrenia than control subjects were unemployed and single (p<0.05). Individuals with schizophrenia scored significantly higher on the SASI, ASAQ, and CTQ (p<0.05), whereas the control subjects scored significantly higher on the WHOQoL-BREF (p<0.05). ASAQ scores had mild positive correlations with total PANSS and PANSS subscale scores, and moderate positive correlations with total CTQ, CTQ emotional subscale scores, and CTQ physical abuse subscale scores. A negative moderate correlation was found between ASAQ and total WHOQoL-BREF scores. Mediation analysis revealed that CTQ scores significantly affected total WHOQoL-BREF and ASAQ scores. The model pathway for ASAQ scores showed a significant direct and indirect effect of CTQ on the total WHOQoL-BREF scores. Childhood trauma predicts adult separation anxiety disorder, which partially mediates the impact of childhood trauma on quality of life in individuals with schizophrenia. Therapeutic interventions for adult separation anxiety disorder in individuals with schizophrenia and a history of childhood trauma may help increase their quality of life.

A study of association between serum testosterone levels and clinical aspects of schizophrenia

Background: Sex disparities in schizophrenia especially in negative symptoms may be related to the action of sex steroid hormones. Objective: The purpose of this study was to analyze relationship of serum testosterone levels with respect to clinical psychopathology laying emphasis on negative symptoms in male patients with schizophrenia. Material and Methods: The study population consisted of two hundred male schizophrenia patients and fifty- age matched healthy individuals. Sociodemographic data and history of illness were noted in semi-structured proforma. Clinical psychopathology was assessed by Positive and Negative Syndrome Scale (PANSS). Drug Induced Extrapyramidal Symptoms Scale (DIEPSS) and Calgary Depression Scale for Schizophrenia (CDSS) were also used to exclude the effects of extrapyramidal symptoms and depression. Serum testosterone level was measured by chemiluminescence method. Data were analyzed by chi square test (x2) and z-test. Pearson’s correlation analysis was used for association of testosterone level with PANSS sub-scale scores. Results: Mean testosterone level was significantly lower in schizophrenia patients (381.90±158.29; p ˭ 0.001) as compared to healthy subjects (520.51±145.94). A significant inverse association was detected between PANSS negative sub scale scores and testosterone levels (r ˭ -0.211, p ˭ 0.034). There was no correlation with other PANSS sub scale items (i.e., positive symptoms, general psychopathology and total scores), age of onset and disease duration. Conclusion: The present study indicates that lower level of testosterone may have a role in presentation of negative symptoms in schizophrenia, and the pathophysiological processes of disease affected the testosterone levels. Therefore, clinicians are advised to monitor levels of testosterone in patients with predominant negative symptoms of schizophrenia and enquire about sexual dysfunction and infertility. Lower level of sex steroids is a point of concern as these patients are at high risk of osteoporosis and cardiovascular co-morbidities. In near future therapeutic strategies targeting testosterone could be useful in ameliorating the negative symptoms of disease.

Effectiveness of Lurasidone 80 mg in Patients with Schizophrenia: Results of an Open-Label, 12-Week Extension Study.

To evaluate the effectiveness and safety of lurasidone 80 mg/day (versus the 40 mg/day dose) during a 12-week, open-label extension study in patients with an acute exacerbation of schizophrenia who had completed a 6-week double-blind study of lurasidone. A total of 289 adult patients with schizophrenia completed the double-blind study and enrolled in the 12-week extension study. Lurasidone was flexibly dosed at 40 or 80 mg/day. Effectiveness measures included the Positive and Negative Syndrome Scale (PANSS) subscale scores, Clinical Global Impression-Severity Scale (CGI-S), and Calgary Depression Scale for Schizophrenia (CDSS), analyzed based on last observation carried forward (LOCF-endpoint). Safety/tolerability assessments included adverse events, body weight, laboratory tests, and discontinuation due to adverse events. Mean endpoint change was greater for lurasidone in modal doses of 80 mg/d (N=136) vs 40 mg/d (N=153) on the PANSS positive subscale (-3.0 vs -2.3), PANSS negative subscale (-1.9 vs -1.7), PANSS General Psychopathology subscale (-5.1 vs -3.8), the CGI-S score (-0.5 vs -0.4), and the CDSS score (-0.7 vs -0.1). Discontinuation rates due to adverse events on lurasidone modal 80 mg/d vs 40 mg/d were 4.4% vs 7.2%; and the most common adverse events in the modal 80 mg/d group were nasopharyngitis, 7.4% (vs 4.6% on modal 40 mg/d), constipation, 5.9% (vs 2.0%), and headache, 5.9% (vs 2.0%). In patients with acute schizophrenia treated with lurasidone 40 mg/d, increasing the dose to 80 mg/d was well tolerated, and was associated with greater improvement in PANSS subscale scores compared to continued treatment with a dose of 40 mg/d.

Alterations in innate immune defense distinguish first-episode schizophrenia patients from healthy controls.

Innate immune components involved in host defense have been implicated in schizophrenia (SCZ). However, studies exploring their clinical utility in SCZ diagnosis are limited. The main purpose of this study was to evaluate whether circulating endotoxin, high mobility group box 1 protein (HMGB1) and complement component 4 (C4) could act as peripheral biomarkers to distinguish first-episode schizophrenia (FES, n = 42) patients from healthy controls (HCs, n = 35) in associations with psychopathological symptoms and cognitive dysfunctions. Also, their changes after 8-week antipsychotic treatment were investigated. The Positive and Negative Syndrome Scale (PANSS), Psychotic Symptom Rating Scale (PSYRATS), and MATRICS Consensus Cognitive Battery (MCCB) were administered. Receiver operating characteristic (ROC) curves were conducted to evaluate the diagnostic effectiveness of the three biological indicators. Compared to HCs, levels of endotoxin, HMGB1, and C4 were remarkably increased in FES patients after controlling for age, gender, body mass index (BMI) and education years, and the combination of the three biomarkers demonstrated desirable diagnostic performance (AUC = 0.933). Moreover, the endotoxin level was positively correlated with the severity of auditory hallucinations. After 8 weeks of treatment, HMGB1 was decreased significantly in patients but still higher than that in HCs, whereas endotoxin and C4 did not change statistically. The baseline levels of endotoxin, HMGB1, and C4, as well as their changes were not associated with changes in any PANSS subscale score and total score. Our preliminary results suggest that a composite peripheral biomarker of endotoxin, HMGB1, and C4 may have accessory diagnostic value to distinguish SCZ patients from HCs. Additionally, endotoxin might be implicated in the pathogenesis of auditory hallucinations.

Delayed improvements in visual memory task performance among chronic schizophrenia patients after high-frequency repetitive transcranial magnetic stimulation.

BACKGROUNDCognitive impairments are core characteristics of schizophrenia, but are largely resistant to current treatments. Several recent studies have shown that high-frequency repetitive transcranial magnetic stimulation (rTMS) of the left dor-solateral prefrontal cortex (DLPFC) can reduce negative symptoms and improve certain cognitive deficits in schizophrenia patients. However, results are inconsistent across studies.AIMTo examine if high-frequency rTMS of the DLPFC can improve visual memory deficits in patients with schizophrenia.METHODSForty-seven chronic schizophrenia patients with severe negative symptoms on stable treatment regimens were randomly assigned to receive active rTMS to the DLPFC (n = 25) or sham stimulation (n = 22) on weekdays for four consecutive weeks. Patients performed the pattern recognition memory (PRM) task from the Cambridge Neuropsychological Test Automated Battery at baseline, at the end of rTMS treatment (week 4), and 4 wk after rTMS treatment (week 8). Clinical symptoms were also measured at these same time points using the Scale for the Assessment of Negative Symptoms (SANS) and the Positive and Negative Syndrome Scale (PANSS).RESULTSThere were no significant differences in PRM performance metrics, SANS total score, SANS subscores, PANSS total score, and PANSS subscores between active and sham rTMS groups at the end of the 4-wk treatment period, but PRM performance metrics (percent correct and number correct) and changes in these metrics from baseline were significantly greater in the active rTMS group at week 8 compared to the sham group (all P < 0.05). Active rTMS treatment also significantly reduced SANS score at week 8 compared to sham treatment. Moreover, the improvement in visual memory was correlated with the reduction in negative symptoms at week 8. In contrast, there were no between-group differences in PANSS total score and subscale scores at either week 4 or week 8 (all P > 0.05).CONCLUSIONHigh-frequency transcranial magnetic stimulation improves visual memory and reduces negative symptoms in schizophrenia, but these effects are delayed, potentially due to the requirement for extensive neuroplastic changes within DLPFC networks.

Facial affect recognition in first-episode psychosis is impaired but not associated with psychotic symptoms

IntroductionSocial dysfunction is a key feature of psychotic disorders such as schizophrenia linked to disability. Less is known about social functioning in the early stages of the disorder and if there is an association to psychotic symptoms. AimsInvestigate if antipsychotic drug-naïve or briefly medicated individuals with first-episode psychosis (FEP), have impaired facial affect recognition (FAR) compared to control participants and if psychotic symptoms are associated with the FAR ability. MethodIndividuals with FEP (n = 67) and control participants (n = 51) performed a computer-aided FAR task on basic emotions. Psychotic symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Group performances were compared using age and gender as covariates. The associations between FAR and performance on the subscales of PANSS were analyzed. ResultsCompared to control participants, individuals with FEP were impaired in general FAR (Beta = -2.04 [95 % conf: -3.75/-1.62], p < 0.001) and FAR of negative emotions (Beta = -1.74 [95 % conf: -3.08/-1.22], p < 0.001), driven by difficulties in recognition of anger and disgust. In both groups, there was a pattern of mistaking negative emotions for other negative emotions. There were no significant group differences in FAR of happiness. No significant associations between FAR and psychotic symptoms were observed. DiscussionThe results indicate that FAR, an underlying mechanism of social functioning is impaired early in the course of psychotic disorders. Current findings do not support the hypothesis that misinterpretation of facial expressions in individuals with FEP underlies or contributes to symptoms of psychosis.

Add-On Pramipexole for the Treatment of Schizophrenia and Schizoaffective Disorder: A Randomized Controlled Trial.

Objective: Several small clinical trials have reported that the dopamine agonist pramipexole was beneficial in treating patients with schizophrenia. A confirmatory trial was conducted to test this hypothesis.Methods: This 16-week, multicenter, double-blind, randomized, placebo-controlled study included 200 subjects meeting DSM-IV-TR criteria for schizophrenia or schizoaffective disorder. Patients were randomized to receive either pramipexole (0.75 mg twice daily, n = 100) or placebo (n = 100) as an add-on to their regular antipsychotic treatment. The primary outcome measure was the total score on the Positive and Negative Syndrome Scale (PANSS); secondary outcome measures included PANSS subscale and cognitive functioning scores. Recruitment was performed in 30 sites in Romania and 1 site in the Republic of Moldova between January and June 2011.Results: Analysis of covariance models showed no significant difference between pramipexole and placebo for total PANSS (P > .99) and PANSS positive (P > .99), negative (P = .73), and general psychopathology (P = .99) subscale scores. Changes in Clinical Global Impressions-Severity of Illness scale and Brief Assessment of Cognition in Schizophrenia scores showed no significant difference between pramipexole and placebo.Conclusions: The results of this large randomized controlled trial indicated that pramipexole was not efficacious as an add-on to antipsychotic medications for schizophrenia.Trial Registration: ClinicalTrials.gov identifier NCT01320982.

Exploring the link between cognitive deficit, self-esteem, alexithymia, and depressive symptom of schizophrenia.

ObjectiveTo the best of our knowledge, studies have been rarely conducted to assess the correlation between cognitive deficit, self‐esteem, and alexithymia in the depressive symptoms of schizophrenia (SCZ). Therefore, this study aims to explore the risk factors associated with impairment of cognitive function, alexithymia, and self‐esteem among a representative sample of first‐episode schizophrenic patients.MethodWe recruited 107 first‐episode schizophrenic patients (48.6% male, 51.4% female, 36.94 ± 10.73 years) into the research group, according to the Diagnostic and Statistical Manual of Mental Disorders (5th edition). A total of 45 healthy people (51.1% male, 48.9% female, 32.47 ± 10.94 years) were enlisted in the healthy control group. Psychotic symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS). Cognitive functions were estimated using the Montreal Cognitive Assessment Scale (MoCA). The feelings of respect and self‐acceptance were tested using the Rosenberg Self‐Esteem Scale (RSES). Emotion of identifying and describing were measured by self‐report scale of Toronto Alexithymia Scale‐20 (TAS‐20).ResultsOverall cognitive impairment and alexithymia were found more serious in the patients of SCZ than the healthy group (p < .001, respectively). The patients of SCZ have higher self‐esteem than the healthy group (p = .013). Total score of MoCA, ability of visual space and executive function, and delayed recall were explored had negatively correlation with alexithymia (r = −.319, p = .001; r = −.248, p = .010; r = −0.263, p = .006). Total score of RSES and depressive symptoms of PANSS had a positive correlation with alexithymia (r = .394, p = .001; r = .208, p = .032). Stepwise regression analyses have shown a positive relationship between difficulty describing feelings and depression subscale of PANSS (β = .188, t = −2.007, p = .047) while a negative relationship between externally oriented thinking and depression subscale of PANSS (β = −.244, t = −2.603, p = .011). A positive link correlation also was found between the total scores of TAS and RSES (β = .372, t = 4.144, p = .001). A negative relevance was found between the total scores of TAS and scores of MoCA (β = −.305, t = −3.348, p = .001).ConclusionOverall impairment of cognitive function and alexithymia are commonly encountered in SCZ patients. Poor cognitive function, alexithymia, and high level self‐esteem may be specific detective risk factors for the depressive symptoms of SCZ.

Comparison of Acute Followed by Maintenance ECT vs Clozapine on Psychopathology and Regional Cerebral Blood Flow in Treatment-Resistant Schizophrenia: A Randomized Controlled Trial.

In treatment-resistant schizophrenia (TRS), Clozapine is only approved treatment with undesirable side-effects, warranting better alternatives. Our hypothesis is acute followed by maintenance Electroconvulsive Therapy (M-ECT) will be comparable in efficacy and safety to Clozapine in TRS. In this open-label trial, 60 TRS patients were randomized equally to M-ECT (following an acute-course) or Clozapine. Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Schizophrenia Scale (CGI-SCH), Montreal Cognitive Assessment (MoCA), and Global assessment of functioning (GAF) were measured and compared within and between the groups at baseline, 6 weeks, 12 weeks, and 24 weeks. SPECT-CT brain was done at baseline and 24 weeks to compare the changes in regional cerebral perfusion between the groups and correlate with the changes in the outcome-measures. The PANSS-T scores changes from baseline over the observation-points were significant in both M-ECT and clozapine groups (P < .001), with comparatively better reduction with M-ECT (P < .001). Similar trends were observed in PANSS subscales, CGI-SCH and GAF in both groups, with significantly better improvement with M-ECT over the study-period. After 24 weeks, there was significantly better perfusion with M-ECT in bilateral prefrontal and temporal cortices (P < .05). With M-ECT, a positive correlation was found between changes in PANSS-P scores and left-lateral Temporal cortical perfusion (r = .465, P = .017). Acute followed by M-ECT was more effective than clozapine over 6 months in reducing the positive and negative symptoms, general psychopathology, illness-severity, and improving the global functionality in TRS [clinicaltrials.gov: NCT03807882].

Improvement of adjunctive berberine treatment on negative symptoms in patients with schizophrenia.

The upregulation of immune and inflammatory response may play a role in the negative symptoms of schizophrenia. Berberine is an effective drug with anti-inflammatory property, and may be beneficial for the treatment of negative symptoms. The aim of this study is to test this hypothesis through a randomized, double-blind, placebo-controlled, clinical trial. Eligible patients with schizophrenia were randomized to receive placebo or berberine (900mg/day) for 8weeks as adjunctive treatment to single atypical antipsychotic drug. The Positive and Negative Syndrome Scale (PANSS) was used to evaluate clinical symptoms at three time points (baseline, 4th and 8th week). Blood samples were collected at the above three time points to determine the concentrations of inflammatory markers including interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP). 59 patients with intention-to-treat were analyzed, 32 in the berberine group and 27 in the placebo group. From the baseline to the 8th week, berberine treatment significantly improved the negative symptom subscale of PANSS (F = 18.981; p < 0.001). From the baseline to the 8th week, the plasma CRP concentration decreased in the berberine group, while increased in the placebo group (F = 5.373; p = 0.024). Furthermore, in the berberine group, the change of CRP concentration was significantly positively correlated with the change of PANSS negative symptom subscale within 8weeks (r = 0.56; p = 0.002). There was no significant difference in adverse events between the two groups (p's > 0.05). Our study suggests that berberine treatment is well tolerated in patients with schizophrenia. Berberine may improve negative symptoms through anti-inflammatory effect.Trial registration: Clinicaltrials.gov identifier: NCT03548155.

CRP and its relation to cognitive performance in schizophrenia patients: a cross-sectional study

Background Schizophrenia (SZ) is one of the most severe and chronic forms of mental illness. It involves cognition, emotion, perception, and behavior. There is an obvious role of neuroinflammation and immunogenetics in SZ. There is a relation between the severity of cognitive deficits and enhanced levels of inflammatory markers in schizophrenic patients, including C-reactive protein (CRP). Also, a relation between CRP and the negative-symptom subscale of Positive and Negative Syndrome Scale (PANSS) was observed.Aims To study the relation between CRP level with different cognitive domains in patients with SZ and its relation to the psychopathology of SZ.Methods A cross-sectional study was applied on 40 SZ patients and 40 healthy controls, serum CRP was measured, and they were cognitively assessed using Arabic version of Montreal Cognitive Assessment Basic (MoCA-B).Results SZ patients showed worse cognitive performance on all subtests (except orientation), MOCA-B, and the total score when compared with normal controls. A negative correlation between executive functions, calculation, abstraction, memory, naming, and attention subtests of MoCA-B and its total score with the serum CRP was found. A positive correlation between CRP and the negative subscale and total score of PANSS was found.Conclusions Serum CRP level was elevated in patients with SZ when compared with healthy controls and significantly negatively correlated with cognitive functions, and positively correlated with negative symptoms in SZ patients, which seconds the neuroinflammatory etiology of SZ.