Negative Symptom Domains Research Articles

Clinician-Reported Negative Symptom Scales: A Systematic Review of Measurement Properties.

Negative symptoms of schizophrenia are correlated with reduction of normal function and lower quality of life. They were newly defined by the NIMH-MATRICS Consensus in 2005, dividing the rating tools to assess them into first-generation scales, developed before the Consensus, and second-generation scales, based on the recently introduced definitions. The COnsensus-based Standards for the selection of health Measurement Instrument (COSMIN) guidelines for systematic reviews were used to evaluate the quality of psychometric data of the first-generation scales that cover the 5 negative symptom domains of the NIMHS Consensus: the Scale for the Assessment of Negative Symptoms (SANS), the High Royds Evaluation of Negativity Scale (HEN), and the Negative Symptom Assessment-16 (NSA-16). The search strategy resulted in the inclusion of a total of 13 articles, 7 for the SANS, 4 for the NSA-16, and 2 for the HEN. For the SANS and the NSA-16, the overall results of the scales' measurement properties are mostly insufficient or indeterminate. The quality of evidence for the HEN is poor, due to a small number of validation studies/included patients. After applying the COSMIN guidelines, we do not recommend the usage of these first-generation scales to rate negative symptoms. At the minimum they require further validation.

Season of birth/C-reactive protein gene interaction differentially affects negative symptoms domains in patients with schizophrenia

Season of birth/C-reactive protein gene interaction differentially affects negative symptoms domains in patients with schizophrenia

Predicting treatment resistance in positive and negative symptom domains from first episode psychosis: Development of a clinical prediction model

BackgroundTreatment resistance (TR) in schizophrenia may be defined by the persistence of positive and/or negative symptoms despite adequate treatment. Whilst previous investigations have focused on positive symptoms, negative symptoms are highly prevalent, impactful, and difficult to treat. In the current study we aimed to develop easily employable prediction models to predict TR in positive and negative symptom domains from first episode psychosis (FEP). MethodsLongitudinal cohort data from 1027 individuals with FEP was utilised. Using a robust definition of TR, n = 51 (4.97 %) participants were treatment resistant in the positive domain and n = 56 (5.46 %) treatment resistant in the negative domain 12 months after first presentation. 20 predictor variables, selected by existing evidence and availability in clinical practice, were entered into two LASSO regression models. We estimated the models using repeated nested cross-validation (NCV) and assessed performance using discrimination and calibration measures. ResultsThe prediction model for TR in the positive domain showed good discrimination (AUC = 0.72). Twelve predictor variables (male gender, cannabis use, age, positive symptom severity, depression and academic and social functioning) were retained by each outer fold of the NCV procedure, indicating importance in prediction of the outcome. However, our negative domain model failed to discriminate those with and without TR, with results only just over chance (AUC = 0.56). ConclusionsTreatment resistance of positive symptoms can be accurately predicted from FEP using routinely collected baseline data, however prediction of negative domain-TR remains a challenge. Detailed negative symptom domains, clinical data, and biomarkers should be considered in future longitudinal studies.

Illness-related variables and abnormalities of resting-state brain activity in schizophrenia.

The development of neuroimaging biomarkers in patients with schizophrenia (SCZ) requires a refined clinical characterization. A limitation of the neuroimaging literature is the partial uptake of progress in characterizing disease-related features, particularly negative symptoms (NS) and cognitive impairment (CI). In the present study, we assessed NS and CI using up-to-date instruments and investigated the associations of abnormalities in brain resting-state (rs)-activity with disease-related features. Sixty-two community-dwelling SCZ subjects participated in the study. Multiple regression analyses were performed with the rs-activity of nine regions of interest as dependent variables and disease-related features as explanatory variables. Attention/vigilance deficits were negatively associated with dorsal anterior cingulate rs-activity and, together with depression, were positively associated with right dorsolateral prefrontal cortex rs-activity. These deficits and impairment of Reasoning/problem-solving, together with conceptual disorganization, were associated with right inferior parietal lobule and temporal parietal junction rs-activity. Independent of other features, the NS Expressive Deficit domain was associated with the left ventral caudate, while the Motivational Deficit was associated with the dorsal caudate rs-activity. Neurocognitive deficits and the two negative symptom domains are associated with different neural markers. Replications of these findings could foster the identification of clinically actionable biomarkers of poor functional outcomes.

Comparison of Negative Symptom Network Structures Between Patients With Early and Chronic Schizophrenia: A Network and Exploratory Graph Analysis.

Despite the clinical relevance of negative symptoms in schizophrenia, our understanding of negative symptoms remains limited. Although various courses and stages of schizophrenia have been identified, variations in the negative symptom networks between distinct stages of schizophrenia remain unexplored. We examined 405 patients with early schizophrenia (ES) and 330 patients with chronic schizophrenia (CS) using the Scale for the Assessment of Negative Symptoms. Network analysis and exploratory graph analysis were used to identify and compare the network structures and community memberships of negative symptoms between the two groups. Further, associations between communities and social functioning were evaluated. The potential influences of other symptom domains and confounding factors were also examined. Multidimensional differences were found in the networks of negative symptoms between ES and CS. The global connectivity strength was higher in the network of ES than in the network of CS. In ES, central symptoms were mainly related to expressive deficits, whereas in CS they were distributed across negative symptom domains. A three-community structure was suggested across stages but with different memberships and associations with social functioning. Potential confounding factors and symptom domains, including mood, positive, disorganization, and excitement symptoms, did not affect the network structures. Our findings revealed the presence of stage-specific network structures of negative symptoms in schizophrenia, with negative symptom communities having differential significance for social functioning. These findings provide implications for the future development of tailored interventions to alleviate negative symptoms and improve functionality across stages.

An exploration of blood-based biomarkers of negative symptoms of psychosis in men

Negative symptoms in the context of psychosis are still poorly understood and diagnosed, which impairs the treatment efficacy of current therapies and patient's integration in society. In this study, we aimed to test hypothesis-based and exploratory associations of negative symptom domains, as defined by the Brief Negative Symptom Scale (BNSS), with hormonal and hematological variables, and, complementarily, with standard psychological/cognitive and psychopathological measures. Fifty-one male patients diagnosed with a psychotic disorder underwent a structured interview and blood collection. Standard Spearmen bivariate correlations were used for data analysis. We obtained evidence of hypothesis-based associations between specific negative symptoms and oxytocin, thyroid stimulating hormone levels and neutrophil-to-lymphocyte ratio; as well as novel and hypothesis-free associations with erythrocyte and lymphocyte count, mean corpuscular volume and red cell distribution width. Complementarily, we also obtained some validation of previous associations of negative symptoms with illness resolution, cognitive symptom severity and social performance, and a novel association with anger contagion. We hope our results can generate new hypotheses in psychosis research. Our work suggests further avenues in research on erythrocytic, inflammatory, thyroid and oxytocin-related markers and abnormalities in psychosis, especially in regards to specific negative symptoms, towards more precise and comprehensive etiological, diagnostic and therapeutic models.

Emotional tone in clinical high risk for psychosis: novel insights from a natural language analysis approach.

Individuals at clinical high risk (CHR) for psychosis experience subtle emotional disturbances that are traditionally difficult to assess, but natural language processing (NLP) methods may provide novel insight into these symptoms. We predicted that CHR individuals would express more negative emotionality and less emotional language when compared to controls. We also examined associations with symptomatology. Participants included 49 CHR individuals and 42 healthy controls who completed a semi-structured narrative interview. Interview transcripts were analyzed using Linguistic Inquiry and Word Count (LIWC) to assess the emotional tone of the language (tone -the ratio of negative to positive language) and count positive/negative words used. Participants also completed clinical symptom assessments to determine CHR status and characterize symptoms (i.e., positive and negative symptom domains). The CHR group had more negative emotional tone compared to healthy controls (t=2.676, p=.009), which related to more severe positive symptoms (r2=.323, p=.013). The percentages of positive and negative words did not differ between groups (p's>.05). Language analyses provided accessible, ecologically valid insight into affective dysfunction and psychosis risk symptoms. Natural language processing analyses unmasked differences in language for CHR that captured language tendencies that were more nuanced than the words that are chosen.

The polymorphism ZNF804A rs1344706 is differentially associated with negative symptoms domains in schizophrenia

IntroductionNegative symptoms (NS) are an important clinical characteristic of schizophrenia. In recent years, clinical research on NS has focused on their clinical heterogeneity. Based on two-factor analysis, it has been proposed to divide NS into abulia-apathy (AA) and expressive deficit (ED) domains. A number of studies have shown that these domains have different effects on the clinical features of schizophrenia, which suggests different pathophysiological mechanisms of their development. Neurobiological differences between AA and DE have been identified in neuroimaging and immunological studies but there is less research on the genetic background of NS.ObjectivesTo search for an association between the rs1344706 polymorphism of the zinc finger protein gene (ZNF804A) and the AA and ED subdomains. The rs1344706 polymorphism is one of the best-supported risk variants for schizophrenia. The risk genotype AA has been shown to be associated with clinical presentations of the disease.MethodsThe study included 1116 (741 (66.3% women) patients with schizophrenia. The diagnosis was made according to ICD-10 criteria (item F20). The average age of the patients was 38.4 (13.6) years, age at disease onset was 26.1 (10.6) years. NS were assessed with the PANSS. The PANSS-derived AA domain consisted of Emotional withdrawal (PANSS item N2), Apathetic social withdrawal (N4), Active social avoidance (G16). The DE domain included Blunted affect (N1), Poor rapport (N3), Lack of spontaneity (N6), Mannerism and posturing (G5), Motor retardation (G7), Disturbance of volition (G13). Genotyping of the ZNF804A rs1344706 polymorphism was carried out using HRM-PCR. ANOVA with genotype and sex as independent variables, and age at the time of disease manifestation and its duration as covariates was used. Post hoc tests were performed using Bonferroni correction.ResultsA significant effect of the rs1344706 polymorphism on the severity of symptoms in the AA domain was revealed (F=5.88, df=2, p=0.002). In carriers of the CC genotype, the severity of symptoms was significantly lower than in carriers of the AA genotype and the AC genotype (8.4(3.5), 9.4(7.4) and 8.8(3.5) points, respectively). This effect was independent of sex and was not mediated by age at onset or duration of disease. There was no effect of the rs1344706 polymorphism on the severity of symptoms in the ED domain.ConclusionsThe association of the ZNF804A rs1344706 (A/C) polymorphism with NS of schizophrenia has not been reported so far though some studies have found the effect of this polymorphism on PANSS positive symptoms and PANSS total score. The finding of the association with NS can be explained by the fact that the NS heterogeneity was taken into account in the present study.Disclosure of InterestNone Declared

Variations of Sleep Patterns and Their Relations with Positive and Negative Domains of Schizophrenia in Eastern Indian Population

Abstract Objectives: Schizophrenia is a persistent and incapacitating psychiatric condition characterized by symptoms with positive, negative, affective, and cognitive domains. Sleep disturbances represent an important facet of this disorder, impacting both the quality of life and influencing its overall outcome. In the cross-sectional study, we intended to investigate the polysomnographic findings of patients with schizophrenia showing predominantly positive symptoms as opposed to those presenting with predominantly negative symptoms and also as compared to normal population. Methods: This study had a cross-sectional design, involving the recruitment of 60 medication-naive patients diagnosed with schizophrenia according to the ICD-10 criteria and 30 study participants representing normal population. The cases were subdivided into two groups: one characterized by predominantly positive symptoms and the other characterized by predominantly negative symptoms. Both the groups received overnight polysomnography, and study variables were recorded. Results: All the sleep parameters were deranged in patients with schizophrenia as compared to normal controls in the general population, with significantly more pronounced differences found in those with predominant positive symptoms for most variables (p < 0.001). The only exception was the duration of N3 (slow-wave sleep) which was significantly decreased in patients with negative symptoms compared to those with positive symptoms (p < 0.001). But no significant differences were found between the negative and positive symptom domain groups in mean rapid eye movement (REM) latency, duration of N1 and N2 sleep, and total percentage of REM sleep. Conclusion: This study highlights substantial variations in sleep patterns between the negative and positive symptom domains of schizophrenia and also as compared to the general population. Further study is imperative to explore the link between circadian integrity and symptoms of the various domains of schizophrenia.

Knockdown of Lhx6 during embryonic development results in neurophysiological alterations and behavioral deficits analogous to schizophrenia in adult rats

A decreased expression of specific interneuron subtypes, containing either the calcium binding protein parvalbumin (PV) or the neurotransmitter somatostatin (SST), are observed in the cortex and hippocampus of both patients with schizophrenia and rodent models used to study the disorder. Moreover, preclinical studies suggest that this loss of inhibitory function is a key pathological mechanism underlying the symptoms of schizophrenia. Interestingly, decreased expression of Lhx6, a key transcriptional regulator specific to the development and migration of PV and SST interneurons, is seen in human postmortem studies and following multiple developmental disruptions used to model schizophrenia preclinically. These results suggest that disruptions in interneuron development in utero may contribute to the pathology of the disorder. To recapitulate decreased Lhx6 expression during development, we used in utero electroporation to introduce an Lhx6 shRNA plasmid and knockdown Lhx6 expression in the brains of rats on gestational day 17. We then examined schizophrenia-like neurophysiological and behavioral alterations in the offspring once they reached adulthood. In utero Lhx6 knockdown resulted in increased ventral tegmental area (VTA) dopamine neuron population activity and a sex-specific increase in locomotor response to a psychotomimetic, consistent with positive symptomology of schizophrenia. However, Lhx6 knockdown had no effect on social interaction or spatial working memory, suggesting behaviors associated with negative and cognitive symptom domains were unaffected. These results suggest that knockdown of Lhx6 during development results in neurophysiological and behavioral alterations consistent with the positive symptom domain of schizophrenia in adult rats.

Optimal values exploration for responsiveness rates in stable and unstable schizophrenic patients

Background: Schizophrenia leads to multifunctional disability, characterized by cognitive and social impairments, everyday skill and self-assessment difficulties, and negative symptoms. Long-term clinical stability, often achieved with antipsychotics, improves everyday functioning. Aim: The goal is to determine to determine the efficacy of different antipsychotic classes (%Prob of APDs' Resp) and adherence rates, as measured by the Behavioural Adherence Rating Scale (BARS). Methods: The study focuses on schizophrenia-spectrum disorders in adults and elderly psychiatric patients, using established diagnostic systems. The observational and retrospective study will be conducted at the Princess Aisha Bint Al Hussein Medical Centre from January 2021 to January 2023. The study will use positive and negative symptom domains to measure initial severity and assess ideal values for antipsychotic drugs. A Chi Square test will be used to analyze distribution rates and odds ratios. The study will use SPSS version 25 with a 5% significance level. Results: The binary logistic regression model was created using patient adherence patterns evaluated using BARS. The model aimed to predict positive responsiveness (Δ PANSS≥20%) and negative responsiveness (Δ PANSS<20%) using patient data. The model accurately identified 94.4% of cases, with a chi-square value of 4.412 and a p-value of 0.818. BARS testing revealed a probable range of APDs' reaction from 64.4% to 88.2%, with individuals determining this range. The study suggests that the specific range may be different depending on the Cox & Snell R2 or Nagelkerke R2 procedures used, but all factors should be considered. The model's accuracy is significant, and the findings suggest that individuals are responsible for determining this range. Conclusion: The study reveals that psychotic individuals require 68.5% adherence for optimal responsiveness. Adding LAIAP to oral APDs enhances responsiveness.

Negative symptoms and social cognition as mediators of the relationship between neurocognition and functional outcome in schizophrenia.

In this study we assessed the contribution of psychopathology, including the two domains of negative symptoms (motivational deficit and expressive deficit), processing speed as an index of neurocognition, and emotion recognition, as an index of social cognition, to poor functional outcomes in people with schizophrenia. The Positive and Negative Syndrome Scale was used to evaluate positive symptoms and disorganization and the Brief Negative Symptom Scale to assess negative symptoms. The Symbol Coding and the Trail Making Test A and B were used to rate processing speed and the Facial Emotion Identification Test to assess emotion recognition. Functional outcome was assessed with the Personal and Social Performance Scale (PSP). Regression analyses were performed to identify predictors of functional outcome. Mediation analyses was used to investigate whether social cognition and negative symptom domains fully or partially mediated the impact of processing speed on functional outcome. One hundred and fifty subjects from 8 different European centers were recruited. Our data showed that the expressive deficit predicted global functioning and together with motivational deficit fully mediated the effects of neurocognition on it. Motivational deficit was a predictor of personal and social functioning and fully mediated neurocognitive impairment effects on the same outcome. Both motivational deficit and neurocognitive impairment predicted socially useful activities, and the emotion recognition domain of social cognition partially mediated the impact of neurocognitive deficits on this outcome. Our results indicate that pathways to functional outcomes are specific for different domains of real-life functioning and that negative symptoms and social cognition mediate the impact of neurocognitive deficits on different domains of functioning. Our results suggest that both negative symptoms and social cognition should be targeted by psychosocial interventions to enhance the functional impact of neurocognitive remediation.

Negative Symptoms and Their Associations With Other Clinical Variables and Working Memory Across the Schizophrenia Spectrum and Bipolar Disorder.

Negative symptoms (NS) of schizophrenia spectrum disorders (SSD) are also prevalent in bipolar disorder I (BD-I) and show associations with impaired working memory (WM). However, empirical work on their relationship to other clinical factors across SSD and BD-I is sparse. Here, we characterized the associations of NS with key clinical variables and WM capacity across a combined sample of SSD and BD. We included 50 outpatients with SSD and 49 with BD-I and assessed NS domains using SANS global scores for avolition-apathy, anhedonia-asociality, alogia, and blunted affect. We assessed the transdiagnostic relationship between NS and other clinical variables, including positive symptoms, disorganization, depressive symptoms, and antipsychotic medication, using multiple regressions. The strength of these associations was further determined through dominance analyses. Finally, we used multiple regression to assess the relationship between NS domains and WM. To assess the generalizability of transdiagnostic associations, analyses were repeated in each diagnostic group separately. Across SSD and BD-I, disorganization was associated with avolition-apathy and anhedonia-asociality and depressive symptoms additionally predicted anhedonia-asociality. Antipsychotic dose was associated with blunted affect while group differences only predicted alogia. Higher avolition-apathy was related to impaired WM transdiagnostically, partially mediated by the severity of disorganization, whereas only in BD-I higher anhedonia-asociality was associated with better WM capacity. This study demonstrated transdiagnostic associations of both avolition-apathy and anhedonia-asociality with disorganization and identified avolition-apathy as a potential transdiagnostic predictor of WM impairments. Overall, our findings highlight the importance of understanding the relationship between NS domains and other clinical factors with cognitive function across SSD and BD.

Rationale and Challenges for a New Instrument for Remote Measurement of Negative Symptoms.

There is a broad consensus that the commonly used clinician-administered rating scales for assessment of negative symptoms share significant limitations, including (1) reliance upon accurate self-report and recall from the patient and caregiver; (2) potential for sampling bias and thus being unrepresentative of daily-life experiences; (3) subjectivity of the symptom scoring process and limited sensitivity to change. These limitations led a work group from the International Society of CNS Clinical Trials and Methodology (ISCTM) to initiate the development of a multimodal negative symptom instrument. Experts from academia and industry reviewed the current methods of assessing the domains of negative symptoms including diminished (1) affect; (2) sociality; (3) verbal communication; (4) goal-directed behavior; and (5) Hedonic drives. For each domain, they documented the limitations of the current methods and recommended new approaches that could potentially be included in a multimodal instrument. The recommended methods for assessing negative symptoms included ecological momentary assessment (EMA), in which the patient self-reports their condition upon receipt of periodic prompts from a smartphone or other device during their daily routine; and direct inference of negative symptoms through detection and analysis of the patient's voice, appearance or activity from audio/visual or sensor-based (eg, global positioning systems, actigraphy) recordings captured by the patient's smartphone or other device. The process for developing an instrument could resemble the NIMH MATRICS process that was used to develop a battery for measuring cognition in schizophrenia. Although the EMA and other digital measures for negative symptoms are at relatively early stages of development/maturity and development of such an instrument faces substantial challenges, none of them are insurmountable.

External validation of the five domains of negative symptoms: Focus on cognition, functional capacity, and real-world functioning.

The conceptualization of negative symptoms (NS) in schizophrenia is still controversial. Recent confirmatory factor-analytic studies suggested that the bi-dimensional model (motivational deficit [MAP] and expressive deficit [EXP]) may not capture the complexity of NS structure, which could be better defined by a five-factor (five NS domains) or a hierarchical model (five NS domains as first-order factors, and MAP and EXP, as second-order factors). A validation of these models is needed to define the structure of NS. To evaluate the validity and temporal stability of the five-factor or the hierarchical structure of the brief negative symptom scale (BNSS) in individuals with schizophrenia (SCZ), exploring associations between these models with cognition, social cognition, functional capacity, and functioning at baseline and at 4 years follow-up. Clinical variables were assessed using state-of-the-art tools in 612 SCZ at two-time points. The validity of the five-factor and the hierarchical models was analyzed through structural equation models. The two models had both a good fit and showed a similar pattern of associations with external validators at the two-time points, with minor variations. The five-factor solution had a slightly better fit. The associations with external validators favored the five-factor structure. Our findings suggest that both five-factor and hierarchical models provide a valid conceptualization of NS in relation to external variables and that five-factor solution provides the best balance between parsimony and granularity to summarize the BNSS structure. This finding has important implications for the study of pathophysiological mechanisms and the development of new treatments.

The longitudinal structure of negative symptoms in treatment resistant schizophrenia

Background and hypothesisThe negative symptoms of schizophrenia are strong prognostic factors but remain poorly understood and treated. Five negative symptom domains are frequently clustered into the motivation and pleasure (MAP) and emotional expression (EE) ‘dimensions’, but whether this structure remains stable and behaves as a single entity or not remains unclear. Study designWe examined a cohort of 153 patients taking clozapine for treatment-resistant schizophrenia in a regional mental health clinic. Patients were assessed longitudinally over a mean period of 45 months using validated scales for positive, negative and mood symptoms. Network analyses were performed to identify symptom ‘communities’ and their stability over time. The influence of common causes of secondary negative symptoms as well as centrality measures were also examined. Study resultsAcross patients at baseline, two distinct communities matching the clinical domains of MAP and EE were found. These communities remained highly stable and independent over time. The communities remained stabled when considering psychosis, depression, and sedation severity, and these causes of secondary negative symptoms were clustered into the MAP community. Centrality measures also remained stable over time, with similar centrality measures across symptoms. ConclusionsOur results suggest that MAP and EE are independent dimensions that remain highly stable over time in chronic schizophrenia patients treated with clozapine. Common causes of secondary negative symptoms mapped onto the MAP dimension. Our results emphasise the need for clinical trials to address either MAP or EE, and that treating causes of secondary negative symptoms may improve MAP.

The association between dissociative symptoms and schizophrenia-related negative symptoms: A transdiagnostic approach

Negative symptoms of schizophrenia remain clinically and theoretically understudied and represent an unmet psychiatric need. Negative symptoms are assumed to be related to other psychiatric disorders, but their association with dissociative symptoms is yet to be explored, particularly in light of depression and anxiety symptoms. We examined the five domains of negative symptoms (anhedonia, asociality, avolition, blunted affect and alogia) in an Israeli national sample of 1930 participants of whom 645 (33.4%) were with increased risk for dissociative disorder. The results show that anhedonia, blunted affect and alogia significantly associated with risk for dissociative disorder, above and beyond depression and anxiety. When assessing for negative symptoms it may be worth screening for dissociation and vice versa and thus make a more accurate clinical picture of the interplay between them.

Impact of negative symptoms on health-related quality of life in schizophrenia.

Evidence regarding the association of Negative Symptoms (NS) dimensions with Health-related Quality of Life (HRQoL) is limited and no prior study has looked into contributions of NS domains on HRQoL. This study bridges the gap by examining the associations of NS, its two dimensions (Motivation and Pleasure, and Emotional Expressivity) and five domains (Anhedonia, Avolition, Asociality, Blunted affect and Alogia) with HRQoL in schizophrenia. 274 individuals with schizophrenia were assessed on the Positive and Negative Syndrome Scale (PANSS) and Brief Negative Symptom Scale (BNSS). PANSS scores were mapped to EuroQol five-dimensional (EQ-5D-5L) utility scores using an algorithm previously validated in Singapore, and the resulting EQ-5D-5L scores were used as a measure of HRQoL. Multiple linear regression analyses of the two NS dimensions and five NS domains against EQ-5D-5L showed that a lower severity of NS, specifically that of the Motivation and Pleasure (MAP) dimension and asociality domain was associated with higher HRQoL. Our findings highlight the importance of targeting NS, particularly MAP and asociality, in improving HRQoL in schizophrenia.

Exploring negative symptoms heterogeneity in patients diagnosed with schizophrenia and schizoaffective disorder using cluster analysis

BackgroundDissecting the heterogeneity of schizophrenia may help foster progress in understanding its etiology and lay the groundwork for the development of new treatment options for primary or enduring negative symptoms (NS). In this regard, the present study aimed to: (1) to use cluster analysis to identify subgroups of Lebanese patients diagnosed with either schizophrenia or schizoaffective disorder based on NS clusters, and (2) to relate the statistically-derived subgroups to clinically relevant external validators (including measures if state and trait depression, stigma, insight, loneliness, social support).MethodA total of 202 adult long-stay, chronic, and clinically remitted patients (166 diagnosed with schizophrenia and 36 with schizoaffective disorder) were enrolled. A cluster analysis approach was adopted to classify patients based on the five NS domains social withdrawal, emotional withdrawal, alogia, avolition and anhedonia.ResultsA three-cluster solution was obtained based on unique NS profiles, and divided patients into (1) low NS (LNS; 42.6%) which characterized by the lowest mean scores in all NS domains, (2) moderate NS (MNS; 25.7%), and (3) high NS (HNS; 31.7%). Post-hoc comparisons showed that depression (state and trait), loneliness and social support could accurately distinguish the schizophrenia subgroups. Additionally, individuals in the HNS cluster had longer duration of illness, longer duration of hospitalization, and were given higher dosages of antipsychotic medication compared to those in the other clusters, but these differences did not achieve the statistical significance.ConclusionFindings provide additional support to the categorical model of schizophrenia by confirming the existence of three alternate subtypes based on NS. The determination of distinct NS subgroups within the broad heterogeneous population of people diagnosed with schizophrenia may imply that each subgroup possibly has unique underlying mechanisms and necessitates different treatment approaches.

Effectiveness of Adjuvant Treatment of N-Acetylcysteine on Negative Symptoms and Neutrophil-Lymphocyte Ratio (NLR) in Schizophrenic Patients

Highlights:1. The essence of schizophrenia is the negative symptoms.2. Adding meloxicam can improve the negative symptoms and changes in the NLR in schizophrenic patients. AbstractIntroduction: Schizophrenia is a mental disorder that has a negative symptom domain. Negative symptoms are commonly referred to as the essence of schizophrenia. Treatment of negative symptoms is still considered less than optimal. The ratio of neutrophils and lymphocytes is one of the markers of inflammation. This study aimed to analyze the effectiveness of N-acetylcysteine as adjuvant therapy for improving negative symptoms and changes in the neutrophil-lymphocyte ratio (NLR) in schizophrenic patients. Methods: This was a quasi-experimental study using a single-blind, pretest–post-test design. The subjects were 34 schizophrenic patients who were inpatients at Dr. Arif Zainuddin Regional Mental Hospital (RSJD), Surakarta, from May to July 2020. The subjects were assigned using a purposive sampling technique based on inclusion criteria and received adjuvant N-acetylcysteine therapy at 400 mg/day for 4 weeks. Data collection was obtained from medical records, interviews, field notes, positive scale, negative scale, and general psychopathology scale (PANSS) assessment sheets, and blood NLR examinations. Data analysis used SPSS 25.0.Results: There was a significant difference between the treatment and control groups in reducing negative PANSS subscale measurement after adjuvant N-acetylcysteine treatment. However, there was no significant difference between the control and treatment groups after N-acetylcysteine administration for NLR.Conclusion: The dose of adjuvant therapy N-acetylcysteine given to patients in this study had an effect on decreasing the negative subscale PANSS score.