Brief Negative Symptom Scale Research Articles

Effort-based decision making in schizotypy and its relationship with amotivation and psychosocial functioning.

Suboptimal effort-based decision-making with reduced willingness to expend effort for high-probability/high-value reward is observed in schizophrenia patients and is related to diminished motivation, but is understudied in schizotypy. This study aimed to examine effort-allocation in schizotypy individuals and its association with amotivation and psychosocial functioning. We recruited 40 schizotypy individuals and 40 demographically-matched healthy controls, based on Schizotypal Personality Questionnaire-Brief (SPQ-B) score (top and bottom 10% SPQ-B scores, respectively), from 2400 young people aged 15-24 years participating a population-based mental health survey in Hong Kong and examined effort-allocation using the Effort Expenditure for Reward Task (EEfRT). Negative / amotivation symptoms and psychosocial functioning were assessed by the Brief Negative Symptom Scale (BNSS) and the Social Functioning and Occupational Assessment Scale (SOFAS), respectively. Schizotypy individuals were categorized into high-amotivation and low-amotivation groups based on a median-split of BNSS amotivation domain score. Our results showed no main group effect (in either two or three-group comparison) on effort task performance. Three-group comparison analyses on selected EEfRT performance indices revealed that high-amotivation schizotypy individuals displayed significantly less increase in effortful options from low-value to high-value reward (reward-difference score) and from low-probability/low-value to high-probability/high-value reward (probability/reward-difference score) than low-amotivation individuals and controls. Correlation analyses demonstrated trend-wise significance between BNSS amotivation domain score and several EEfRT performance indices in schizotypy group. Schizotypy individuals with poorer psychosocial functioning tended to exhibit smaller probability/reward-difference score relative to other two groups. Our findings indicate subtle effort-allocation abnormalities in schizotypy individuals with high levels of diminished motivation, and suggest the link between laboratory-based effort-cost measures and real-world functional outcome.

The Associations of Neutrophil-Lymphocyte, Platelet-Lymphocyte, Monocyte-Lymphocyte Ratios and Immune-Inflammation Index with Negative Symptoms in Patients with Schizophrenia.

Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR) and systemic immune-inflammation index (SII index) are increasingly used as indicators of inflammation in different conditions, including schizophrenia. However, their relationship with negative symptoms, including anhedonia, is largely unknown. Included were 200 patients with schizophrenia and 134 healthy controls (HC), assessed for physical anhedonia (PA), using the Revised Physical Anhedonia Scale (RPAS), and social anhedonia (SA) by the Revised Social Anhedonia Scale (RSAS). Patients were rated by the Positive and Negative Syndrome Scale (PANSS), the Clinical Assessment Interview for Negative Symptoms (CAINS) and the Brief Negative Symptom Scale (BNSS). Most of the negative symptoms were in a weak to moderate positive correlations with blood cell inflammatory ratios, namely, between NLR and MLR with PANSS negative scale, CAINS, and BNSS, and in male patients, between PLR and PANSS negative scale and CAINS. Fewer correlations were detected in females, but also in a positive direction. An exception was SA, given the negative correlation between its severity and the SII index in females, and its presence and higher PLR in males. While different negative symptoms were associated with subclinical inflammation, the relationship between SA and lower inflammatory markers deserves further exploration.

The Role of Two Factors of Negative Symptoms and Cognition on Social Functioning in Male Patients with Schizophrenia: A Mediator Model

This study aims to compare the cognitive function and social functioning in male patients with deficit syndrome (DS) and non-DS, and to explore whether cognitive function serves as a mediator in the relationship between the two factors of negative symptoms (motivation and pleasure (MAP) and expressivity (EXP) deficits, and social functioning in schizophrenia patients. One hundred and fifty-six male patients with schizophrenia and 109 age- and education-matched normal controls were enrolled in the current study. The Chinese version of a Schedule for Deficit Syndrome (SDS) was used for DS and non-DS categorization. The Brief Psychiatric Rating Scale (BPRS) and the Brief Negative Symptoms Scale (BNSS) were used to assess psychotic and negative symptoms in patients. The Social-Adaptive Functioning Evaluation (SAFE) was adopted to evaluate patients' social functioning, and a battery of classical neurocognitive tests was used to assess cognition, including sustained vigilance/attention, cognitive flexibility, ideation fluency, and visuospatial memory. We found that male patients with DS performed worse in all four cognitive domains and social functioning compared to non-DS patients. Both total negative symptoms and its two factors were significantly associated with all four domains of cognition and social functioning in male patients. Interestingly, our results indicate that only cognitive flexibility mediates the relationship between negative symptoms and social functioning in schizophrenia patients, but there were no differences between EXP and MAP negative factors in this model. Our findings suggest that DS patients may represent a unique clinical subgroup of schizophrenia, and the integrated interventions targeting both negative symptoms and cognition, especially cognitive flexibility, may optimally improve functional outcomes in schizophrenia patients.

Community-based multi-site randomized controlled trial of behavioral activation for patients with negative symptoms of schizophrenia

BackgroundNegative symptoms are closely related to the poor prognosis of schizophrenia, for which there is no effective treatment to date. Behavioral activation (BA), which is an effective treatment for depression, is a behavioral approach that targets low levels of response-contingent positive reinforcement. This study aimed to explore BA as an effective intervention for relieving the negative symptoms of schizophrenia. MethodsThis was a randomized single-blind controlled trial. Eighty-four patients with schizophrenia were enrolled in community mental health settings. Excluding 14 patients who opted out of the study, 70 were randomly assigned to receive BA in addition to treatment-as-usual (BA + TAU) or treatment-as-usual (TAU) only. Negative symptoms were assessed using the Clinical Assessment Interview for Negative Symptoms (CAINS) and Brief Negative Symptom Scale (BNSS) at baseline, post-treatment, and 6-months follow-up. ResultsSignificant differences between the BA + TAU and TAU only groups were observed in the measures of negative symptoms post-treatment. The total score of CAINS was significantly decreased after BA treatment (η2 = 0.13). The tendency of the BA + TAU treatment effect was also observed for the BNSS total score and PANSS negative symptom subscale (η2 = 0.10 and η2 = 0.11, respectively). However, the difference between the two groups was not sustained at the six-month follow-up. ConclusionsOur findings suggest that BA could be a promising time-limited and structured psychosocial intervention for schizophrenia-associated negative symptoms with the merit of easy dissemination. Further studies are needed to examine the factors involved in sustaining improvement.

Comparative Assessment of Effect on Psychomotor Performance Efficacy and Adherence of Levosulpiride and Olanzapine in Patients with Schizophrenia: A Parallel, Open-label, Prospective Observational Study

Abstract Context: Schizophrenia is mostly treated with atypical antipsycotics, which may be required for lifetime. Olanzapine is commonly used in this condition, whereas levosulpiride is approved in India for the same. Knowing the effect of these drugs on psychomotor function helps in choosing a suitable drug to a particular patient based on his daily activities. Aims: The aim is to compare the effect of levosulpiride and olanzapine on psychomotor performance, efficacy, and adherence in patients with schizophrenia. Settings and Design: This was open-label, parallel arm, prospective observational study carried out in a tertiary care hospital of central India from December 2019 to December 2021. Subjects and Methods: Thirty-six patients visiting psychiatry OPD, diagnosed by treating psychiatrist as schizophrenia were assessed by CFFT, hand steadiness test (HST), arithmetic ability test, and reaction time (RT) for psychomotor function, and symptoms were scored on positive and negative syndrome scale (PANSS) and brief negative symptom scale (BNSS) rating scales at the first visit, end of 4 and 8 weeks. Adherence was assessed by the Medication adherence rating scale at 8 weeks. Results: Statistically significant increase in RT was seen in both levosulpiride (P = 0.04) and olanzapine (P = 0.0065) groups, whereas only the olanzapine group had a significant change in CFFT (P = 0.04) and HST (P = 0.01) at 8 weeks. On head-to-head comparison, a statistically significant worsening in HST score (P = 0.01) was seen in olanzapine group. Both the groups had significant decreases in all PANSS (P < 0.001) and BNSS (P < 0.001) scores. When change in PANSS and BNSS scores were compared with each other, the levosulpiride group had a significantly more decrease in scores on PANSS negative scale (P = 0.03). Patients in both groups were adherent to treatment. Conclusions: Our study concluded that levosulpiride is better than olanzapine on its fine motor control. Both the drugs increase RT while only olanzapine worsened fine motor control and CFF. Both the drugs were effective for schizophrenia with 8 weeks treatment, while levosulpiride is superior to olanzapine in improving negative symptoms of schizophrenia.

Vocal acoustic features may be objective biomarkers of negative symptoms in schizophrenia: A cross-sectional study

BackgroundThere are currently no objective biomarkers that allow the quantification of negative symptoms of schizophrenia. This study therefore explored the use of acoustic features in identifying the severity of negative symptoms in patients with schizophrenia. MethodsWe recruited 79 inpatients who were diagnosed with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (the schizophrenia group) at the Huilongguan Hospital in Beijing, China, and 79 healthy controls from the surrounding community (the control group). We assessed the clinical symptoms of the patients with schizophrenia using the Positive and Negative Syndrome Scale (PANSS) and the Brief Negative Symptom Scale (BNSS) and recorded the voice of each participant as they read emotionally positive, neutral, and negative texts. The Praat software was used to analyse and extract acoustic characteristics from the recordings, such as jitter, shimmer, and pitch. The acoustic differences between the two groups of participants and the relationship between acoustic characteristics and clinical symptoms in the patient group were analysed. ResultsThere were significant differences between the schizophrenia and control groups in pitch, voice breaks, jitter, shimmer, and the mean harmonics-to-noise ratio (p < 0.05). Jitter was negatively correlated with the blunted affect and alogia subscale scores of the BNSS, both in the positive and neutral emotion conditions, but the correlation disappeared in the negative emotion condition. However, shimmer exhibited a stable negative correlation with the blunted affect and alogia subscale scores of the BNSS in all three emotion conditions. A linear regression analysis showed that pitch, jitter, shimmer, and age were statistically significant predictors of BNSS subscale scores. ConclusionsAcoustic emotional expression differs between patients with schizophrenia and healthy controls. Some acoustic characteristics are related to the severity of negative symptoms, regardless of semantic emotions, and may therefore be objective biomarkers of negative symptoms. A systematic method for assessing vocal acoustic characteristics could provide an accurate and feasible means of assessing negative symptoms in schizophrenia. TweetAcoustic emotional expression differs between patients with schizophrenia and healthy controls. A systematic method for assessing vocal acoustics could provide an accurate and feasible means of assessing negative symptoms in schizophrenia.

A-172 Evaluating Associations Between the Five Negative Symptom Domains and Cognition in Schizophrenia

Abstract Objective: Recently, factor analysis has supported a five-factor model of negative symptoms in schizophrenia (anhedonia, avolition, alogia, asociality, and blunted affect). Associations between these unique negative symptom domains and neurocognition are yet to be examined. The following study investigates relationships between the five distinct negative symptoms and cognitive functioning. Methods: Outpatients diagnosed with schizophrenia (n=245) were assessed during periods of clinical stability for negative symptom severity using the Brief Negative Symptom Scale (BNSS). The MATRICS Consensus Cognitive Battery (MCCB) was used to assess seven domains of neurocognition, including processing speed, working memory, verbal learning, visual learning, reasoning, problem solving, and social cognition. To evaluate external correlates, the five-domain negative symptoms were correlated with measures of neurocognition. Results: Greater negative associations were found between the five negative symptom domains with processing speed, attention, working memory, social cognition, and overall MCCB scores. Correlational analyses demonstrated the strongest negative relationships between the domain of attention with alogia and blunted affect. Conclusions: The present study examined unique associations between cognitive abilities and the five negative symptom domains. Strong negative associations were found between negative symptoms and distinct measures of neurocognition, indicating a unique variance in cognitive performance correlates with severity of negative symptoms. Results suggest greater severity of negative symptoms is associated with greater impairments in select neurocognitive domains. Further research using analytic approaches would offer additional support for this hypothesis. Findings have implications for developing differential treatments targeting the five negative symptom domains separately, as they may have distinct underlying pathophysiological and neurocognitive mechanisms.

Bridge centrality network structure of negative symptoms in people with schizophrenia.

Negative symptoms are complex psychopathology. Although evidence generally supported the NIMH five consensus domains, research seldom examined measurement invariance of this model, and domain-specific correspondence across multiple scales. This study aimed to examine the interrelationship between negative symptom domains captured by different rating scales, and to examine the domain-specific correspondence across multiple scales. We administered the Brief Negative Symptom Scale (BNSS), the Self-evaluation of Negative Symptoms (SNS), and the Scale for Assessment of Negative Symptoms (SANS) to 204 individuals with schizophrenia. We used network analysis to examine the interrelationship between negative symptom domains. Besides regularized partial correlation network, we estimated bridge centrality indices to investigate domain-specific correspondence, while taking each scale as an independent community. The regularized partial correlation network showed that the SNS nodes clustered together, whereas the SANS and the BNSS nodes intermingled together. The SANS attention domain lied at the periphery of the network according to the Fruchterman-Reingold algorithm. The SANS anhedonia-asociality (strength = 1.48; EI = 1.48) and the SANS affective flattening (strength = 1.06; EI = 1.06) had the highest node strength and EI. Moreover, the five nodes of the BNSS bridged the nodes of the SANS and the SNS. BNSS blunted affect (strength = 0.76; EI = 0.76) and SANS anhedonia-asociality (strength = 0.76; EI = 0.74) showed the highest bridge strength and bridge EI. The BNSS captures negative symptoms and bridges the symptom domains measured by the SANS and the SNS. The three scales showed domain-specific correspondence.

Validation of the Turkish version of the self-evaluation of negative symptoms scale (SNS)

Objectives The Self-Evaluation of Negative Symptoms Scale (SNS) is a self-report scale that evaluates a patient’s subjective experience on all five domains of the negative symptoms. This study aimed to present the adaptation and validation study of the Turkish version of SNS(SNS-TR). Methods Seventy-five patients and 50 controls were recruited for this study. After the approval of the translation, participants were asked to fill out SNS-TR by themselves. They were interviewed with the Brief Negative Symptoms Scale (BNSS), Positive and Negative Syndrome Scale (PANSS), and Calgary Depression Scale for Schizophrenia (CDSS). Results SNS-TR showed good internal consistency in the reliability analysis with Cronbach’s alpha= 0.873. Subscale-total score correlation coefficients were significant (p < 0.01). In the validity analyses, the total and subscale scores of SNS-TR showed positive correlations with the total and subscales of BNSS, with only one exception of BNSS lack of distress subscales. The total score of SNS-TR demonstrated a significant correlation with PANSS-total, PANSS-negative subscale, PANSS-general subscale, and CDSS scores. Confirmatory factor analysis showed acceptable values for the five-factor structure, similar to the original version. Conclusion To conclude, our study indicates that SNS-TR is an easily applicable self-evaluation tool with good psychometric properties for assessing negative symptoms. KEY POINTS SNS is a novel and easily applicable self-report scale for examining negative symptoms in schizophrenia patients, allowing them to evaluate their subjective experience on all five domains of the negative symptoms. It shows good internal consistency (α= 0.873) which is similar to the original version (α = 0.867). Confirmatory factor analysis scores were found in acceptable ranges and SNS-TR confirm the five-factor structure. Using this scale in clinical practice would empower both the physician’s examinations and patient participation through treatment and follow-up course.

A double-blind, randomized, placebo-controlled proof of concept study of the efficacy and safety of Lu AF11167 for persistent negative symptoms in people with schizophrenia

Lu AF11167 is a selective, high-affinity inhibitor of PDE10A that modulates dopamine D1 and D2 receptor-mediated intraneuronal signalling without binding to these receptors. This randomized, double-blind, parallel-group, placebo-controlled study (NCT03793712) with open-label extension (NCT03929497) evaluated the efficacy of two fixed-flexible doses (1-2mg/day and 3-4mg/day) of Lu AF11167 in stable, non-acute patients with schizophrenia and persistent prominent negative symptoms. The studies were discontinued following a futility analysis of the double-blind study, and we report data collected up to study termination. Of the 210 patients screened, 162 were randomized, 111 completed the double-blind study and 96 entered the open-label study before early termination. The withdrawal rate due to impending relapse was low and comparable across treatment groups (n = 2-4 per group in the double-blind study and n = 1 in the open-label extension). Double-blind treatment with Lu AF11167 3-4mg was not superior to placebo in the reduction of Brief Negative Symptom Scale (BNSS) total scores from Baseline to Week 12 (primary endpoint); adjusted mean changes were -6.8 with placebo, -5.7 with Lu AF11167 1-2 mg group and -6.0 with Lu AF11167 3-4mg. Treatment with Lu AF11167 1-2mg also failed to separate from placebo on the primary endpoint. Neither dose group showed significant improvements versus placebo on any of the secondary efficacy measures exploring effect of treatment on overall symptomology, negative symptoms, positive symptoms, or functioning. Administration of Lu AF11167 was safe and well tolerated and adverse events were not a major reason for withdrawal from the study.

Pilot Study of the Brief Negative Symptom Scale (BNSS) as a method for evaluation the required form of social service: institutional or non-institutional one

IntroductionPsychiatric care for persons suffering from chronic mental disorders and unable to live independently involves an assessment of their need for a certain form of social service. In Russia patients with schizophrenia account for over 40 % of all persons living in residential facilities for persons with mental disability (Kekelidze, 2020). Their clinical picture is most often determined by negative symptoms, which makes it advisable to use the BNSS scale (Kirkpatrick, 2011).ObjectivesPilot testing of the BNSS scale in patients, living in residential facilities for persons with mental disability.MethodsWith Russian-language version of the BNSS scale (Mucci, 2019; Papsuev, 2020); CGI-S; Standardized protocol of forensic psychiatric examination in cases of deprivation, restriction, restoration of legal capacity (Kharitonova, 2021) we examined 15 persons (Age: M=54,2; SD=8,6) suffering from schizophrenia and living in residential facilities.ResultsIn three subjects the BNSS survey was not possible. The remaining 12 had a total score from 6 to 61 (M = 29.08; Med = 25; Std.Dev. = 17.98) with maximum score in the Asociality subscale (Item 6: M = 3.25; Med = 4; Std.Dev. = 1.76). CGI-S significantly correlated with indicators on the scales «Avolition: inner experience» (r = 0.68, p &lt;0.05), «Blunted affect : vocal expression» (r = 0.64, p &lt;0.05). According to full examination community-based services were recommended for two women with BNSS overall score 6 and 11.ConclusionsOur pilot study demonstrated that the BNSS can be successfully used as one of methods in comprehensive examination to determine the form of social services.DisclosureNo significant relationships.

European Validation of the Self-Evaluation of Negative Symptoms (SNS): A Large Multinational and Multicenter Study.

BackgroundNegative symptoms are usually evaluated with scales based on observer ratings and up to now self-assessments have been overlooked. The aim of this paper was to validate the Self-evaluation of Negative Symptoms (SNS) in a large European sample coming from 12 countries. We wanted to demonstrate: (1) good convergent and divergent validities; (2) relationships between SNS scores and patients' functional outcome; (3) the capacity of the SNS compared to the Brief Negative Symptom Scale (BNSS) to detect negative symptoms; and (4) a five-domain construct in relation to the 5 consensus domains (social withdrawal, anhedonia, alogia, avolition, blunted affect) as the best latent structure of SNS.MethodsTwo hundred forty-five subjects with a DSM-IV diagnosis of schizophrenia completed the SNS, the Positive and Negative Syndrome Scale (PANSS), the BNSS, the Calgary Depression Scale for Schizophrenia (CDSS), and the Personal and Social Performance (PSP) scale. Spearman's Rho correlations, confirmatory factor analysis investigating 4 models of the latent structure of SNS and stepwise multiple regression were performed.ResultsSignificant positive correlations were observed between the total score of the SNS and the total scores of the PANSS negative subscale (r = 0.37; P < 0.0001) and the BNSS (r = 0.43; p < 0.0001). SNS scores did not correlate with the level of insight, parkinsonism, or the total score of the PANSS positive subscale. A positive correlation was found between SNS and CDSS (r = 0.35; p < 0.0001). Among the 5 SNS subscores, only avolition subscores entered the regression equation explaining a lower functional outcome. The 1-factor and 2-factor models provided poor fit, while the 5-factor model and the hierarchical model provided the best fit, with a small advantage of the 5-factor model. The frequency of each negative dimension was systematically higher using the BNSS and the SNS vs. the PANSS and was higher for alogia and avolition using SNS vs. BNSS.ConclusionIn a large European multicentric sample, this study demonstrated that the SNS has: (1) good psychometric properties with good convergent and divergent validities; (2) a five-factor latent structure; (3) an association with patients' functional outcome; and (4) the capacity to identify subjects with negative symptoms that is close to the BNSS and superior to the PANSS negative subscale.

Defining negative symptoms remission in schizophrenia using the Brief Negative Symptom Scale

IntroductionThis study aimed to propose criteria for negative symptoms remission (NSR) in schizophrenia using the Brief Negative Symptom Scale (BNSS). Material and methods274 participants were assessed on the Positive and Negative Syndrome Scale (PANSS), BNSS and Social and Occupational Functioning Assessment Scale (SOFAS). Two criteria for NSR on the BNSS were proposed – NSR based on the BNSS domains scores (NSRBNSS_DOMAINS) and NSR based on 5 key items of the BNSS (NSRBNSS_5ITEMS). A SOFAS score of 61 and above was considered as functional remission (FR). Logistic regressions were run to examine the association between FR and NSR. Receiver operating characteristic (ROC) curve analysis was performed for the NSR criteria on FR. Kappa agreement statistic was used to evaluate the agreement between the two NSR criteria. ResultsEighty-nine (32.5%) participants fulfilled NSRBNSS_DOMAINS criterion whereas 70 (25.6%) participants fulfilled NSRBNSS_5ITEMS criterion. The two NSR criteria had substantial agreement (Kappa statistic=0.797) with each other. Sixty-one (25.3%) participants were in FR. FR was significantly associated with NSR, irrespective of the criterion used. To predict FR, the Area Under the Curve for NSRBNSS_DOMAINS and NSRBNSS_5ITEMS were 0.761 (CI: 0.696–0.826, p<0.001) and 0.723 (CI: 0.656–0.790, p<0.001), respectively. Hence, both NSR criteria demonstrated a fair ability to discriminate between functional remitters and non-remitters. ConclusionsDepending on the setting and needs, clinicians and researchers might employ either the full BNSS or an abbreviated 5-item BNSS scale to identify NSR in schizophrenia. More research is needed to further examine the validity of these criteria in schizophrenia.

Association of Negative Symptoms of Schizophrenia Assessed by the BNSS and SNS Scales With Neuropsychological Performance: A Gender Effect.

Objective: The relationship between negative symptoms and neurocognitive performance in schizophrenia is well documented, but the mechanism of these connections remains unclear. The study aims to measure the relationship between the results on the new scales for the assessment of negative symptoms such as Brief Negative Symptom Scale (BNSS) and Self-evaluation of Negative Symptoms (SNS), and the results of some neurocognition tests. The second aim is to assess a possible gender effect on these associations.Methods: The study included 80 patients (40 men, 40 women) with schizophrenia, aged 19–63 (mean 38 years), during the improvement period (total PANSS score <80, unchanged pharmacological treatment in the last 3 weeks). They were assessed using the BNSS, SNS, Personal and Social Performance (PSP) scales, and the tests for neuropsychological performance such as the Trail Making Test (TMT-A, TMT-B), Stroop Color-Word Interference Test, Verbal fluency tests (VFT), Category fluency test (CFT), and Digit Symbol Substitution Test (DSST).Results: Male patients obtained higher scores than females on some PANSS and BNSS items. No gender differences were observed for the SNS scale. Female patients scored better in the PSP and CFT. In male patients, a significant positive correlation between the intensity of negative symptoms measured by the BNSS and the results of PSP with the Trail Making Test was observed. In female patients, we found a positive correlation between the results of BNSS and PSP with the Stroop Color-Word Interference Test.Conclusion: The obtained results confirm the relationship between negative symptoms and neurocognition in schizophrenia patients. However, in male and female patients such association was observed for different cognitive domains. Further research is needed to explain the nature of these differences.

Tracing Links Between Early Auditory Information Processing and Negative Symptoms in Schizophrenia: An ERP Study.

Background: Negative symptoms represent a heterogeneous dimension with a strong impact on functioning of subjects with schizophrenia (SCZ). Five constructs are included in this dimension: anhedonia, asociality, avolition, blunted affect, and alogia. Factor analyses revealed that these symptoms cluster in two domains: experiential domain (avolition, asociality, and anhedonia) and the expressive deficit (alogia and blunted affect), that might be linked to different neurobiological alterations. Few studies investigated associations between N100, an electrophysiological index of early sensory processing, and negative symptoms, reporting controversial results. However, none of these studies investigated electrophysiological correlates of the two negative symptom domains.Objectives: The aim of our study was to evaluate, within the multicenter study of the Italian Network for Research on Psychoses, the relationships between N100 and negative symptom domains in SCZ.Methods: Auditory N100 was analyzed in 114 chronic stabilized SCZ and 63 healthy controls (HCs). Negative symptoms were assessed with the Brief Negative Symptom Scale (BNSS). Repeated measures ANOVA and correlation analyses were performed to evaluate differences between SCZ and HCs and association of N100 features with negative symptoms.Results: Our findings demonstrated a significant N100 amplitude reduction in SCZ compared with HCs. In SCZ, N100 amplitude for standard stimuli was associated with negative symptoms, in particular with the expressive deficit domain. Within the expressive deficit, blunted affect and alogia had the same pattern of correlation with N100.Conclusion: Our findings revealed an association between expressive deficit and N100, suggesting that these negative symptoms might be related to deficits in early auditory processing in SCZ.

Structure of Negative Symptoms in Schizophrenia: An Unresolved Issue.

Background: Negative symptoms are core features of schizophrenia and very challenging to be treated. Identification of their structure is crucial to provide a better treatment. Increasing evidence supports the superiority of a five-factor model (alogia, blunted affect, anhedonia, avolition, and asociality as defined by the NMIH-MATRICS Consensus); however, previous data primarily used the Brief Negative Symptoms Scale (BNSS). This study, including a calibration and a cross-validation sample (n = 268 and 257, respectively) of participants with schizophrenia, used the Clinical Assessment Interview for Negative Symptoms (CAINS) to explore the latent structure of negative symptoms and to test theoretical and data-driven (from this study) models of negative symptoms.Methods: Exploratory factor analysis (EFA) was carried out to investigate the structure of negative symptoms based on the CAINS. Confirmatory factor analysis (CFA) tested in a cross-validation sample four competing theoretical (one-factor, two-factor, five-factor, and hierarchical factor) models and two EFA-derived models.Result: None of the theoretical models was confirmed with the CFA. A CAINS-rated model from EFA consisting of five factors (expression, motivation for recreational activities, social activities, vocational, and close/intimate relationships) was an excellent fit to the data (comparative fix index = 0.97, Tucker–Lewis index = 0.96, and root mean square error of approximation = 0.07).Conclusions: This study cannot support recent data on the superiority of the five-factor model defined by the NMIH-MATRICS consensus and suggests that an alternative model might be a better fit. More research to confirm the structure of negative symptoms in schizophrenia, and careful methodological consideration, should be warranted before a definitive model can put forward and shape diagnosis and treatment of schizophrenia.

Safety and Effectiveness of SEP−363856 in Schizophrenia: Results of a 6-Month, Open-Label Extension Study

SEP-363856 is a novel psychotropic agent without dopamine D2 receptor occupancy. Although its mechanism of action has not been fully elucidated, preclinical data suggest that agonism at trace amine receptor 1 (TAAR1) and the serotonin 5-H1A receptor contributes to its efficacy. In a double-blind (DB), placebo-controlled study, SEP-363856 demonstrated significant efficacy in the treatment of an exacerbation of schizophrenia (Koblan et al, NEJM 2020; 82:1497-1506). We present results of a 6-month extension study whose aim was to evaluate the safety and effectiveness of longer-term treatment with SEP-363856. Patients with an acute exacerbation of schizophrenia who completed a 4-week, DB, placebo-controlled, flexible-dose (50 or 75 mg) study of SEP-363856 were given the option to enroll in an extension study in which they were treated, open-label (OL), with flexible doses (25/50/75 mg/d) of SEP-363856 for 26-weeks. The primary outcomes were safety measures; effectiveness outcomes were secondary and included the PANSS total score and the Brief Negative Symptom Scale (BNSS) total score. A total of 193 patients completed the 4-week DB study, and 156 (80.8%) were dosed in the OL extension study and received at least one dose of SEP-363856 (safety population). Study completer rate was 66.9%; reasons for discontinuation consisted of adverse event (11.5%), withdrawal of consent (10.2%), lack of efficacy (5.1%), and other (6.4%). 15 patients experienced an SAE: schizophrenia (n=11); acute psychosis (N=1); uterine hemorrhage and suicidal ideation (N=1 each); there were no deaths in the study. Individual AEs with an incidence =2% were schizophrenia (12.2%), headache (11.5%), insomnia (8.3%), anxiety (5.1%), somnolence (4.5%), nasopharyngitis (4.5%), nausea (3.8%), irritability (3.2%), influenza (3.2%), weight decreased (3.2%), and prolactin increased (2.6%). On movement scales, minimal mean change from OL-baseline to Week 26 occurred on the Barnes total score (-0.1), AIMS total score (0.0) and SAS score (-0.1). Mean month 6 change from DB baseline in weight was -0.3 kg. No clinically meaningful median changes were observed at week 26 in metabolic laboratory parameters (total and LDL cholesterol, triglycerides, hemoglobin A1c) or in prolactin levels. During 6 months of OL treatment, one patient had an increase in QTcF =60 msec; no patients had a QTcF interval =480 msec. Treatment with SEP-363856 was associated with significant improvement from OL baseline to week 26 in PANSS total score (-22.6) and BNSS total score (-11.3). Treatment with SEP-363856 was associated with continued improvement from open-label baseline in the PANSS total (-22.6) and BNSS total (-11.3) scores. The most frequently reported adverse events (= 5%) were schizophrenia, headache, insomnia and anxiety. SEP-363856 had minimal effects on weight, lipids, glycemic indices, prolactin, and was associated with minimal risk of extrapyramidal symptom. Sunovion Pharmaceuticals Inc.

Negative symptoms assessment in early intervention settings: Implications for early identification and treatment

Negative symptoms are a core feature of schizophrenia spectrum disorders associated with poor outcomes such as low remission rates and impairments in daily functioning and quality of life in early psychosis. The assessment of negative symptoms in early psychotic disorders is predominantly conducted by use of first-generation scales such as the PANSS and the SANS, along with the SIPS and CAARMS for the psychosis clinical high-risk (CHR) state. Following the progressed conceptualization of negative symptoms, it has, however, been recognized that these scales suffer important methodological limitations. This warrants a use of second-generation scales such as the Brief Negative Symptom Scale (BNSS) and the Clinical Assessment Interview for Negative Symptoms (CAINS) in early intervention settings in order to achieve a more accurate assessment of the negative symptom complex. Advancing the assessment of negative symptoms in early psychosis may also guide more targeted intervention approaches aimed at improving functional outcome. Albeit recognizing that negative symptoms constitute an important barrier to a good functional outcome in psychotic disorders, few studies have directly aimed at alleviating negative symptoms in early psychosis. Meta-analytical evidence does, however, exist on the efficacy of the combined treatment modalities incorporated in Early Intervention Services (e.g. intensive and assertive case management, family involvement etc.) in reducing negative symptoms in first-episode psychosis. Evidence on the effect of interventions for improving negative symptoms in the CHR state is lacking. Developing targeted, and possibly more individualized negative symptoms treatment approaches, constitute an essential future research area.DisclosureNo significant relationships.

Validation of the traditional script Chinese version of the brief negative symptom scale.

Negative symptoms are a core feature of schizophrenia and account for much of the long-term morbidity and poor functional outcome of people with schizophrenia. The Brief Negative Symptom Scale (BNSS) was developed to address the main limitations of the existing scales for the assessment of negative symptoms. The BNSS has been translated into Italian, Spanish, German, Turkish and simplified Chinese versions with excellent psychometric properties. In this study, a Chinese (traditional script) version of the Brief Negative Symptom Scale (C-BNSS) was developed and validated to facilitate future research on the Chinese population in Hong Kong. Psychometric properties were examined in 149 individuals with schizophrenia. The C-BNSS showed excellent internal consistency (α = 0.96), high inter-rater reliability (intra-class correlation = 0.98), and high test-retest reliability (Spearman's r = 0.96). Convergent validity was supported by high correlations between C-BNSS total score and subscales with the Scale for Assessment of Negative Symptoms (SANS), Negative Symptom subscale of the Positive and Negative Syndrome Scale (PANSS), and Global Assessment of Functioning (GAF) score. Discriminant validity was supported by low correlations between the C-BNSS total score and the PANSS positive subscale, Calgary Depression Scale, and Simpson-Angus Scale for extrapyramidal symptoms. The C-BNSS showed a five- factor structure on Confirmatory Factor Analysis (CFA), confirming findings of previous studies. Findings indicate that the C-BNSS demonstrates excellent psychometric properties, which are comparable to the original English version. It is a promising instrument for use in clinical trials as well as in clinical practice.

Validation of the Dutch Version of the Brief Negative Symptom Scale.

PurposeThe Brief Negative Symptom Scale (BNSS) was developed to measure negative symptoms of schizophrenia. However, the Dutch translation of this instrument, called the “Korte Schaal voor Negatieve Symptomen” (KSNS), has not yet been validated. This study investigates the validity and reliability of this Dutch version of the instrument.Patients and MethodsThe Psychotic Symptom Rating Scale (PSYRATS), Calgary Depression Scale for Schizophrenia (CDSS), the Health of the Nation Scale (HoNOS) and the KSNS were used for routine outcome monitoring to measure symptoms in 28 patients with a psychotic disorder who were being treated on a long-stay ward.ResultsThe internal consistency of the KSNS is fair to good. The inter-rater reliability is excellent. The concurrent validity is moderate but acceptable. The correlations between the KSNS and scales for depression and positive symptoms were not significant, which indicate good divergent validity.ConclusionDespite the small sample size of the current study, we conclude that the BNSS, called the KSNS in Dutch, appears to be a reliable and valid tool for investigating negative symptoms in detail in patients with psychotic disorders.