Positive And Negative Syndrome Scale General Psychopathology Subscale Scores Research Articles

Relationship between plasma risperidone concentrations and clinical features in chronic schizophrenic patients in China.

Prior studies have noted great variability in the plasma levels of risperidone (RIS). Plasma concentrations of RIS and its active moiety are highly variable and depend on absorption, metabolism, and other predictors of metabolic dysregulation; however, these factors are poorly understood and the association between metabolic change and change in psychopathology is uncertain. To ascertain the characteristics of chronic schizophrenic patients treated with RIS, and to assess their relationship with plasma RIS levels. This was a descriptive cross-sectional study of 50 patients with a diagnosis of schizophrenic psychosis treated with RIS in a psychiatric service. The plasma concentrations of RIS and its metabolite 9-hydroxyrisperidone were determined by high performance liquid chromatography. The patients' demographic and clinical characteristics, and psychopathologies were assessed, and the associations between clinical variables and plasma levels of RIS were explored. Male patients received higher doses of RIS than female ones, but plasma concentrations of RIS and risperidone + 9-hydroxyrisperidone (active moiety) were higher in female patients. Age and the mean scores of the general psychopathology subscale of the Positive and Negative Syndrome Scale (PANSS) were significantly positively correlated with plasma concentrations of risperidone + 9-hydroxyrisperidone adjusted for weight and dose in all 50 subjects. In male subjects, we found a statistically significant positive correlation between the concentrations of risperidone + 9-hydroxyrisperidone in plasma/(dose × kg) and age, mean PANSS negative subscale scores, mean PANSS general psychopathology subscale scores, and mean PANSS total scores. Long-term use of RIS should be closely monitored in older patients and females to minimize the risk of high concentrations which could induce side effects.

Elevated activity of plasma superoxide dismutase in never-treated first-episode schizophrenia patients: Associated with depressive symptoms

Oxidative stress in excess may be engaged in the pathophysiological development of schizophrenia (SCZ). Previous research showed altered activity of superoxide dismutase (SOD) in patients suffering from SCZ, with inconsistent results. However, few studies have analyzed the relationship between SOD activity and psychopathological symptoms in never-treated first-episode (NTFE) patients with SCZ. The activities of manganese SOD (MnSOD) and total SOD were measured in a large sample of 166 NTFE patients with SCZ, and 133 healthy controls. The patients' symptoms were evaluated by the Positive and Negative Syndrome Scale (PANSS), as well as the depressive and cognitive factors originated from the PANSS five-factor model. NTFE patients had significantly higher activities of MnSOD and total SOD than healthy controls (both p < 0.01). Correlation analysis displayed a notably positive correlation between both MnSOD or total SOD activities and the PANSS depressive factor, as well as between MnSOD activity and the PANSS general psychopathology subscale score (all p < 0.05). Stepwise multiple regression analysis revealed that both MnSOD and total SOD were independent factors affecting PANSS depressive factor and PANSS general psychopathology subscale score. Our findings suggest that increased SOD activity may be associated with comorbid depressive symptoms in NTFE patients with SCZ.

138 Efficacy and Safety of SEP-363856, a Novel Psychotropic Agent with a Non-D2 Mechanism of Action, in the Treatment of Schizophrenia

SEP-363856 is a novel psychotropic agent that has shown broad efficacy in animal models of schizophrenia and depression. Its antipsychotic effects appear to be mediated by agonist activity at both trace amine-associated receptor 1 (TAAR1) and 5-HT1A receptors. Notably, SEP-363856 does not bind to any dopaminergic, serotonergic (except 5-HT1A), glutamatergic, or other neuroreceptors thought to mediate the effects of currently available antipsychotics. The aim of this study was to evaluate the efficacy and safety of SEP-363856 in acutely symptomatic patients with schizophrenia. Patients aged 18-40 years meeting DSM-5 criteria for schizophrenia (PANSS total score ≥80) were randomized, double-blind, to 4-weeks of flexible-dose SEP-363856 (50 or 75 mg/d) or placebo. Efficacy measures included the Positive and Negative Syndrome Scale (PANSS) total score (primary), PANSS subscale scores, and the Clinical Global Impressions-Severity (CGI-S) score. Change from baseline in primary and secondary measures were analyzed using a mixed model for repeated measures (MMRM) analysis. Study treatment groups were similar at baseline: SEP-363856 (N=120; male, 64.2%; mean age, 30.0 years; PANSS total score, 101.4) and placebo (N=125; male, 63.2%; mean age, 30.6 years; PANSS total score, 99.7). Least-squares (LS) mean reduction from baseline to week 4 was significantly greater for SEP-363856 vs. placebo on the PANSS total score (-17.2 vs. -9.7; P=0.001; effect size, 0.45), PANSS positive subscale score (-5.5 vs. -3.9; P=0.019; effect size, 0.32), PANSS negative subscale score (-3.1 vs. -1.6; P=0.008; effect size, 0.37), PANSS general psychopathology subscale score (-9.0 vs. -4.7; P<0.001; effect size, 0.51), and the CGI-Severity score (-1.0 vs. -0.5; P<0.001; effect size, 0.52). Discontinuation rates for SEP-363856 vs. placebo were similar overall (21.7% vs. 20.8%) and due to an adverse event (8.3% vs. 6.4%). Change in weight, lipids, glucose and prolactin was similar in SEP-363856 and placebo groups. Adverse events occurring with an incidence ≥2% on SEP-363856 or placebo (with SEP-363856 incidence higher than placebo) were: somnolence (6.7% vs. 4.8%), agitation (5.0% vs. 4.8%), nausea (5.0% vs. 3.2%), diarrhea (2.5% vs. 0.8%), and dyspepsia (2.5% vs. 0%). The proportion of patients who reported any extrapyramidal symptom was 3.3% on SEP-363856 and 3.2% on placebo. In this placebo-controlled study, treatment with SEP-363856, a novel psychotropic agent, was associated with statistically significant and clinically meaningful improvement in schizophrenia symptoms as demonstrated by endpoint change in PANSS total and subscale scores, and CGI-Severity scores. Safety and tolerability findings for SEP-363856 were in general similar to placebo. In particular, SEP-363856 was not associated with extrapyramidal symptoms, akathisia, or hyperprolactinemia, consistent with its non-D2 mechanism of action. NCT02969382. Supported by funding from Sunovion Pharmaceuticals Inc.

Relationship Suicide, Cognitive Functions, and Depression in Patients with Schizophrenia.

The aim of this study was to compare schizophrenic patients with and without a suicide attempt history in terms of sociodemographic and clinical features and cognitive functions and to determine the predictive factors for suicide attempt history. In this study, we assessed and compared 70 patients with schizophrenia, 27 patients with a suicide attempt history, and 43 patients without a suicide attempt history. The cognitive functions of patients were assessed by the Stroop test, Wisconsin Card Sorting Test (WCST), and Rey Auditory Verbal Learning Test. In order to evaluate clinical symptoms, the Positive and Negative Syndrome Scale (PANSS) and Calgary Depression Scale for Schizophrenia (CDSS) were used. In this study, the number of hospitalizations, PANSS general psychopathology subscale score, CDSS total score, suicide item score, and WCST total number of responses (WCST1) were significantly higher among the patients with a suicide attempt history. The WCST1 and CDSS total scores were predicted using the suicide attempt history. Revealing the factors related to suicidal behavior in patients with schizophrenia contributes to the prevention of suicide. Studies with long-term follow-up and with a larger sample group are required for the investigation of relationship suicide, cognitive impairment, which is one of the core symptoms of schizophrenia, and depression.

Influence de la résistance aux hallucinations auditives sur la dépression : étude au moyen du questionnaire révisé des croyances à propos des voix

Beliefs about voices and reactions to voices have been proposed as important variables influencing the course of depression in schizophrenia. Consequences of auditory hallucinations are different according to identity, goals, omnipotence, omniscience, and meanings attributed to voices by the client. Ten to 15 % of the general population experience auditory hallucinations during lifetime without any distress or need for medical care. In addition, neither frequency of voices, nor their topography, influence the emotional consequences of auditory hallucinations experiences, but the relationships to voices. The Revised Belief about Voices Questionnaire analyzes voices along 5 dimensions: malevolence, benevolence, omnipotence, resistance, and engagement. Malevolent voices are related to depression, whereas benevolent voices engender more positive emotions. Subjects usually engage with benevolent voices, and resist to malevolent voices. But resistance strategies are barely efficient and often backfire. Patients resisting to their voices consider them more malevolent and present with more depressive symptoms. This research aims at studying the influence of resistance to auditory hallucinations on depression in a group of patients suffering from schizophrenia and experiencing auditory hallucinations, using the Revised Beliefs About Voices Questionnaire (BAVQ-R). It also provides a study of the psychometrics properties of the French language version of the BAVQ-R. Thirty-eight patients suffering from paranoid schizophrenia, undifferentiated schizophrenia or schizoaffective disorder, have been tested with the French versions of the Revised Beliefs About Voices Questionnaire (BAVQ-R), the Positive and Negative Syndrome Scale (PANSS), and the Calgary Depression Scale for Schizophrenia (CDSS). Each patient presented with auditory hallucinations during the week before evaluation, with a minimum score of 3 on P3 item of PANSS. Mean age was 39.39 years (SD 11.33); mean duration of symptoms was 13.92 years (SD 10.81), and patients' mean history of hospitalizations was 7.66 (SD 9.24). Each patient was receiving an antipsychotic medication at the time of evaluation, with a mean chlorpromazine equivalent dose of 806.69 mg/d (ET 539.51); 18.5 % of patients were receiving serotonin reuptake inhibitor, and 31.57 % once committed a suicide attempt. The French version of the BAVQ-R presents with a satisfying internal consistency (Cronbach's alpha=0.74). Similar to the original version, Malevolence and Resistance, and Benevolence and Engagement dimensions are strongly correlated (r=0.73, and r=0.90, P<0.05, respectively). The BAVQ-R scores correlate with the CDSS (r=0.40, P<0.05) and the PANSS General Psychopathology subscale scores (r=0.44, P<0.05), but not with the Positive and Negative subscales. (r=0.17, and r=0.13, P>0.05, respectively). Correlations and forced entry multiple regressions analyses show that Resistance and Malevolence are both strongly correlated to depression, but Resistance is the only dimension that influences depression. Moreover, clients presenting with depressive symptoms resist more to their auditory hallucinations. Finally, emotional resistance, in comparison to behavioral resistance, is responsible for depression in people suffering from auditory hallucinations. Emotional resistance to auditory hallucinations constitutes the most important variable influencing depression in schizophrenia comparing to what the voices say or are supposed to know, their malevolence or benevolence. Demonstration of the influence of resistance to voices on depression would help the development of new therapeutic practices.

Relationship between brain-derived neurotrophic factor gene C270T polymorphisms and the psychotic symptoms and cognitive functioning of patients with schizophrenia.

BackgroundFindings from previous studies linking brain-derived neurotrophic factor (BDNF) and schizophrenia are inconsistent and few studies have assessed the relationship between BDNF C270T gene polymorphisms and the clinical and cognitive symptoms of schizophrenia.AimCompare the prevalence of the BDNF C270T gene polymorphisms between patients with schizophrenia and controls and, in the patients, assess the relationship of genotypes to the severity of symptoms.MethodsBDNF C270T genotype and allele frequency were measured using Polymerase Chain Reaction methods in 224 drug-free patients with schizophrenia and 220 controls. Psychotic symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS), and cognitive functioning was assessed using the Wisconsin Card Sorting Test (WCST) and the Trail Making Test (TMT). In the patient group, differences in severity of symptoms across the three genotypes (i.e., C/C, C/T, and T/T) of C270T were assessed using one-way analysis of variance.ResultsThe frequency of the T allele was much higher in patients than in controls (15.6% vs. 4.3%, χ2=31.47, p<0.001) and the C/T genotype was more common among patients than controls (27.7% vs. 7.7%, χ2=34.93, p<0.001). Compared to controls, patients performed poorly on all the cognitive tests, but there were no significant differences in the cognitive measures between patients with the three different genotypes. The total PANSS score, the PANSS negative symptoms subscale score, and the PANSS general psychopathology subscale score were not significantly different between the three groups of patients. However, the PANSS positive symptoms subscale score showed a small, statistically significant elevation in the severity of positive symptoms in the C/T genotype compared to the C/C genotype.ConclusionWe confirm previous findings about differences in the prevalence of the BDNF C270T gene polymorphisms in schizophrenia, but do not find strong evidence of a relationship between different genotypes and the severity of the clinical or cognitive symptoms of schizophrenia. Clinical and cognitive symptoms in schizophrenia fluctuate over the course of the illness and with treatment, so stable, individual-specific measures of these parameters (that is, traits) need to be identified before it will be possible to definitively assess their relationship to different genotypes.

Blonanserin for schizophrenia: Systematic review and meta-analysis of double-blind, randomized, controlled trials

BackgroundThere is uncertainty about the efficacy and tolerability of blonanserin in schizophrenia. MethodPubMed, the Cochrane Library databases, PsycINFO, and Google Scholar were searched up to September 2012. A systematic review and meta-analysis of individual patient data from randomized, controlled trials comparing blonanserin with other antipsychotics were conducted. The risk ratio (RR), 95% confidence intervals (CI), numbers-needed-to-harm (NNH), and weighted mean difference (WMD) were calculated. ResultsFour studies (total n = 1080) were identified (vs. risperidone studies [n = 508], vs. haloperidol studies [n = 572]). Comparing blonanserin with other pooled antipsychotics, there were no significant differences in the Positive and Negative Syndrome Scale (PANSS) total score (p = 0.75), PANSS positive (p = 0.41), PANSS negative (p = 0.09), and PANSS general psychopathology subscale scores (p = 0.96), and response rate (p = 0.72). However, blonanserin showed greater efficacy in PANSS negative subscale scores compared with haloperidol (WMD = −1.29, CI = −2.29 to −0.30, p = 0.01, I2 = 0%). No significant differences were found in discontinuation rates between blonanserin and other pooled antipsychotics (due to any cause: p = 0.29, inefficacy: p = 0.32, adverse events: p = 0.56). Blonanserin had a 0.31 lower risk of hyperprolactinemia than the other pooled antipsychotics (CI = 0.20–0.49, NNH = not significant). While dizziness (RR = 0.47, CI = 0.23–0.93, NNH = not significant) and akathisia (RR = 0.54, CI = 0.32–0.90, NNH = 7) occurred significantly less often with blonanserin than with haloperidol, blonanserin had a 1.62 higher risk of akathisia than risperidone (CI = 1.18–2.22, NNH = 3). ConclusionOur results suggest that although blonanserin has a more beneficial effect on negative symptoms than haloperidol, there was a significant difference in the adverse events profile between blonanserin and other antipsychotics.

The efficacy, safety, and tolerability of aripiprazole for the treatment of schizoaffective disorder: Results from a pooled analysis of a sub-population of subjects from two randomized, double-blind, placebo-controlled, pivotal trials

BackgroundSchizoaffective disorder shares clinical characteristics with schizophrenia and affective disorders, with patients experiencing concurrent manic, mixed, or depressive episodes during psychosis. Because efficacy may be better in schizoaffective disorder than schizophrenia, this post-hoc analysis examines the efficacy, safety, and tolerability of aripiprazole in patients with schizoaffective disorder. MethodData were obtained from a sub-sample of subjects with schizoaffective disorder (randomized: aripiprazole n=123, placebo n=56) who participated in two 4-week, multicenter, double-blind trials of subjects with schizophrenia or schizoaffective disorder. Aripiprazole was administered at fixed doses of 15 mg/day, 20 mg/day, or 30 mg/day. Efficacy assessments included the Positive and Negative Syndrome Scale (PANSS) Total score, and the Positive, Negative, and General Psychopathology subscale scores. Safety and tolerability evaluations included incidence of treatment-emergent adverse events and extrapyramidal symptom assessments (SAS, BARS, and AIMS), and metabolic profile changes including weight and BMI. ResultsA significantly greater improvement from baseline to endpoint was observed with aripiprazole compared with placebo on the PANSS Total (–15.9 vs. –3.4; p=0.038) and PANSS Positive subscale (–4.6 vs. –1.0; p=0.027). Differences between treatments were not significant for the PANSS Negative subscale score (–3.7 vs. –1.2; p=0.15) or PANSS General Psychopathology subscale score (–8.3 vs. –3.1; p=0.06). There were no statistically significant differences at endpoint between groups in the mean change from baseline to endpoint in weight, glucose, or total cholesterol, or on SAS, BARS, or AIMS scores. There was a statistically significant decrease in prolactin in subjects treated with aripiprazole compared with placebo (–5.6 vs. –1.3, p<0.001). ConclusionAripiprazole was efficacious and well tolerated in patients with schizoaffective disorder.