Structure of Negative Symptoms in Schizophrenia: An Unresolved Issue.
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SUBMITTER: Russo M
PROVIDER: S-EPMC8712471 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ImportanceNegative symptoms are associated with a range of poor clinical outcomes, and currently available treatments generally do not produce a clinically meaningful response. Limited treatment progress may be owing in part to poor clarity regarding latent structure. Prior studies have inferred latent structure using exploratory factor analysis, which has led to the conclusion that there are 2 dimensions reflecting motivation and pleasure (MAP) and diminished expressivity (EXP) factors. However, whether these conclusions are statistically justified remains unclear because exploratory factor analysis does not test latent structure. Confirmatory factor analysis (CFA) is needed to test competing models regarding the latent structure of a construct.ObjectiveTo evaluate the fit of 4 models of the latent structure of negative symptoms in schizophrenia using CFA.Design, setting, and participantsThree cross-sectional studies were conducted on outpatients with schizophrenia who were rated on the 3 most conceptually contemporary measures: Scale for the Assessment of Negative Symptoms (SANS), Brief Negative Symptom Scale (BNSS), and Clinical Assessment Interview for Negative Symptoms (CAINS). Confirmatory factor analysis evaluated the following 4 models: (1) a 1-factor model; (2) a 2-factor model with EXP and MAP factors; (3) a 5-factor model with separate factors for the 5 domains of the National Institute of Mental Health consensus development conference (blunted affect, alogia, anhedonia, avolition, and asociality); and (4) a hierarchical model with 2 second-order factors reflecting EXP and MAP and 5 first-order factors reflecting the 5 consensus domains.Main outcomes and measuresOutcomes included CFA model fit statistics derived from symptom severity scores on the SANS, BNSS, and CAINS.ResultsThe study population included 860 outpatients with schizophrenia (68.0% male; mean [SD] age, 43.0 [11.4] years). Confirmatory factor analysis was conducted on each scale, including 268 patients for the SANS, 192 for the BNSS, and 400 for the CAINS. The 1- and 2-factor models provided poor fit for the SANS, BNSS, and CAINS as indicated by comparative fit indexes (CFIs) and Tucker Lewis indexes (TLIs) less than 0.950, RMSEAs that exceeded the 0.080 threshold, and WRMRs greater than 1.00. The 5-factor and hierarchical models provided excellent fit, with the 5-factor model being more parsimonious. The CFIs and TLIs met the 0.95 threshold and the 1.00 threshold for both factor models with all 3 measures. Interestingly, the RMSEAs for the 5-factor model and the hierarchical model fell under the 0.08 threshold for the BNSS and the CAINS but not the SANS.Conclusions and relevanceThese findings suggest that the recent trend toward conceptualizing the latent structure of negative symptoms as 2 distinct dimensions does not adequately capture the complexity of the construct. The latent structure of negative symptoms is best conceptualized in relation to the 5 consensus domains. Implications for identifying pathophysiological mechanisms and targeted treatments are discussed.
| S-EPMC6583036 | biostudies-literature
Project description:The negative symptoms have been described in association with schizophrenia since the early days of it being recognized as an entity. However, their elusive nature kept them unacknowledged until there was a revival of interest in them following the development of specific quantifying measures. Over the past three decades, there has been a tremendous surge in research on their types, measurements, status in the present classificatory system, and their implications. The developments in modern investigatory methods have provided the researchers with fresh insights into the underlying mechanisms, and a distributed functioning of the neuronal networks has emerged as the major abnormality. Accordingly, a variety of pharmacological and other treatment modalities have been developed which go beyond the traditional. Nevertheless, a lot remain unanswered. The present paper summarizes important concepts with regard to negative symptoms in schizophrenia.
| S-EPMC5479085 | biostudies-literature
Project description:Prior studies using exploratory factor analysis provide evidence that negative symptoms are best conceptualized as 2 dimensions reflecting diminished motivation and expression. However, the 2-dimensional model has yet to be evaluated using more complex mathematical techniques capable of testing structure. In the current study, network analysis was applied to evaluate the latent structure of negative symptoms using a community-detection algorithm. Two studies were conducted that included outpatients with schizophrenia (SZ; Study 1: n = 201; Study 2: n = 912) who were rated on the Brief Negative Symptom Scale (BNSS). In both studies, network analysis indicated that the 13 BNSS items divided into 6 negative symptom domains consisting of anhedonia, avolition, asociality, blunted affect, alogia, and lack of normal distress. Separation of these domains was statistically significant with reference to a null model of randomized networks. There has been a recent trend toward conceptualizing the latent structure of negative symptoms in relation to 2 distinct dimensions reflecting diminished expression and motivation. However, the current results obtained using network analysis suggest that the 2-dimensional conceptualization is not complex enough to capture the nature of the negative symptom construct. Similar to recent confirmatory factor analysis studies, network analysis revealed that the latent structure of negative symptom is best conceptualized in relation to the 5 domains identified in the 2005 National Institute of Mental Health consensus development conference (anhedonia, avolition, asociality, blunted affect, and alogia) and potentially a sixth domain consisting of lack of normal distress. Findings have implications for identifying pathophysiological mechanisms and targeted treatments.
| S-EPMC6737465 | biostudies-literature
Project description:ObjectiveNegative symptoms are currently viewed as having a 2-dimensional structure, with factors reflecting diminished expression (EXP) and motivation and pleasure (MAP). However, several factor-analytic studies suggest that the consensus around a 2-dimensional model is premature. The current study investigated and cross-culturally validated the factorial structure of BNSS-rated negative symptoms across a range of cultures and languages.MethodParticipants included individuals diagnosed with a psychotic disorder who had been rated on the Brief Negative Symptom Scale (BNSS) from 5 cross-cultural samples, with a total N = 1691. First, exploratory factor analysis was used to extract up to 6 factors from the data. Next, confirmatory factor analysis evaluated the fit of 5 models: (1) a 1-factor model, 2) a 2-factor model with factors of MAP and EXP, 3) a 3-factor model with inner world, external, and alogia factors; 4) a 5-factor model with separate factors for blunted affect, alogia, anhedonia, avolition, and asociality, and 5) a hierarchical model with 2 second-order factors reflecting EXP and MAP, as well as 5 first-order factors reflecting the 5 aforementioned domains.ResultsModels with 4 factors or less were mediocre fits to the data. The 5-factor, 6-factor, and the hierarchical second-order 5-factor models provided excellent fit with an edge to the 5-factor model. The 5-factor structure demonstrated invariance across study samples.ConclusionsFindings support the validity of the 5-factor structure of BNSS-rated negative symptoms across diverse cultures and languages. These findings have important implications for the diagnosis, assessment, and treatment of negative symptoms.
| S-EPMC6403061 | biostudies-literature
Project description:BackgroundDetermining the best latent structure of negative symptoms in schizophrenia could benefit assessment tools, neurobiological research, and targeted interventions. However, no review systematically evaluated studies that assessed and validated latent models of negative symptoms.ObjectiveTo identify and evaluate existing latent structure models in the literature of negative symptoms and to determine the best model.MethodSystematic search of MEDLINE, EMBASE, and Scopus on July 19, 2020, for confirmatory factor analysis models of negative symptoms in patients with schizophrenia. The available evidence was assessed through 2 sets of criteria: (1) study design quality-based on negative symptoms assessment and modeling strategy and (2) psychometric quality and model fit-based on fit indices and factor definition quality.ResultsIn total, 22 studies (n = 17 086) from 9 countries were included. Studies differed greatly regarding symptom scales, setting, and sample size (range = 86-6889). Dimensional models included 2-6 factors (median = 4). Twelve studies evaluated competing models and adopted appropriate instruments to assess the latent structure of negative symptoms. The 5-factor and hierarchical models outperformed unitary, 2-factor, and 3-factor models on all direct comparisons, and most of the analyses derived from the Brief Negative Symptom Scale. Considering the quality criteria proposed, 5-factor and hierarchical models achieved excellent fit in just one study.ConclusionsOur review points out that the 5-factor and hierarchical models represent the best latent structure of negative symptoms, but the immaturity of the relevant current literature may affect the robustness of this conclusion. Future studies should address current limitations regarding psychometric properties and also address biological and clinical validity to refine available models.
| S-EPMC8650068 | biostudies-literature
Project description:OBJECTIVE:The interpretability of results in psychiatric neuroimaging is significantly limited by an overreliance on correlational relationships. Purely correlational studies cannot alone determine whether behavior-imaging relationships are causal to illness, functionally compensatory processes, or purely epiphenomena. Negative symptoms (e.g., anhedonia, amotivation, and expressive deficits) are refractory to current medications and are among the foremost causes of disability in schizophrenia. The authors used a two-step approach in identifying and then empirically testing a brain network model of schizophrenia symptoms. METHODS:In the first cohort (N=44), a data-driven resting-state functional connectivity analysis was used to identify a network with connectivity that corresponds to negative symptom severity. In the second cohort (N=11), this network connectivity was modulated with 5 days of twice-daily transcranial magnetic stimulation (TMS) to the cerebellar midline. RESULTS:A breakdown of connectivity in a specific dorsolateral prefrontal cortex-to-cerebellum network directly corresponded to negative symptom severity. Restoration of network connectivity with TMS corresponded to amelioration of negative symptoms, showing a statistically significant strong relationship of negative symptom change in response to functional connectivity change. CONCLUSIONS:These results demonstrate that a connectivity breakdown between the cerebellum and the right dorsolateral prefrontal cortex is associated with negative symptom severity and that correction of this breakdown ameliorates negative symptom severity, supporting a novel network hypothesis for medication-refractory negative symptoms and suggesting that network manipulation may establish causal relationships between network markers and clinical phenomena.
| S-EPMC6760327 | biostudies-literature
Project description:BackgroundDuring the last decades, a renewed interest for negative symptoms (NS) was brought about by the increased awareness that they interfere severely with real-life functioning, particularly when they are primary and persistent.MethodsIn this guidance paper, we provide a systematic review of the evidence and elaborate several recommendations for the conceptualization and assessment of NS in clinical trials and practice.ResultsExpert consensus and systematic reviews have provided guidance for the optimal assessment of primary and persistent negative symptoms; second-generation rating scales, which provide a better assessment of the experiential domains, are available; however, NS are still poorly assessed both in research and clinical settings.This European Psychiatric Association (EPA) guidance recommends the use of persistent negative symptoms (PNS) construct in the context of clinical trials and highlights the need for further efforts to make the definition of PNS consistent across studies in order to exclude as much as possible secondary negative symptoms. We also encourage clinicians to use second-generation scales, at least to complement first-generation ones.The EPA guidance further recommends the evidence-based exclusion of several items included in first-generation scales from any NS summary or factor score to improve NS measurement in research and clinical settings. Self-rated instruments are suggested to further complement observer-rated scales in NS assessment.Several recommendations are provided for the identification of secondary negative symptoms in clinical settings.ConclusionsThe dissemination of this guidance paper may promote the development of national guidelines on negative symptom assessment and ultimately improve the care of people with schizophrenia.
| S-EPMC8080207 | biostudies-literature
Project description:Schizophrenia is a severe mental disorder characterized by positive and negative symptoms. The negative symptoms are highly relevant to the disease course and outcome. Because negative symptoms show considerable heterogeneity, there is substantial interest in elucidating the negative symptom domains that are characteristic of patient subgroups. It has been proposed that patients with schizophrenia should be classified into deficit and non-deficit groups based on the severity of their negative symptoms. Another method suggested the assessment of the factor structure of negative symptoms to understand its mechanisms. Factor analysis of the different negative symptom rating scales reveals two distinct negative symptom subdomains: diminished expression (DE) and avolition/apathy (AA). These characteristics suggest different pathophysiological mechanisms for the development of AA and DE. We present a large dataset of negative symptom factors calculated for 3006 patients with schizophrenia in the Russian population. Sex, age, age at disease onset and data of birth, including season of birth (SOB), family history of schizophrenia are presented. Negative symptoms were assessed with the Positive and Negative Syndromes Scale (PANSS). We calculated negative symptoms factors as suggested by Liemburg et al. (2013). The data will be useful in assessing the impact of such factors as sex, season of birth (SOB) and family history on the scores of negative symptoms subdomains; such data can help us to better understand the heterogeneity of the negative symptoms of schizophrenia.
| S-EPMC8749170 | biostudies-literature
Project description:Negative symptoms of schizophrenia remain a major therapeutic challenge. The progress in the conceptualization and assessment is not yet fully reflected by treatment research. Nevertheless, there is a growing evidence base regarding the effects of biological and psychosocial interventions on negative symptoms. The importance of the distinction between primary and secondary negative symptoms for treatment selection might seem evident, but the currently available evidence remains limited. Good clinical practice is recommended for the treatment of secondary negative symptoms. Antipsychotic treatment should be optimized to avoid secondary negative symptoms due to side effects and due to positive symptoms. For most available interventions, further evidence is needed to formulate sound recommendations for primary, persistent, or predominant negative symptoms.However, based on currently available evidence recommendations for the treatment of undifferentiated negative symptoms (including both primary and secondary negative symptoms) are provided. Although it has proven difficult to formulate an evidence-based recommendation for the choice of an antipsychotic, a switch to a second-generation antipsychotic should be considered for patients who are treated with a first-generation antipsychotic. Antidepressant add-on to antipsychotic treatment is an option. Social skills training is recommended as well as cognitive remediation for patients who also show cognitive impairment. Exercise interventions also have shown promise. Finally, access to treatment and to psychosocial rehabilitation should be ensured for patients with negative symptoms. Overall, there is definitive progress in the field, but further research is clearly needed to develop specific treatments for negative symptoms.
| S-EPMC8057437 | biostudies-literature
Project description:In chronic psychotic patients, word graph analysis shows potential as complementary psychiatric assessment. This analysis relies mostly on connectedness, a structural feature of speech that is anti-correlated with negative symptoms. Here we aimed to verify whether speech disorganization during the first clinical contact, as measured by graph connectedness, can correctly classify negative symptoms and the schizophrenia diagnosis 6 months in advance. Positive and negative syndrome scale scores and memory reports were collected from 21 patients undergoing first clinical contact for recent-onset psychosis, followed for 6 months to establish diagnosis, and compared to 21 well-matched healthy subjects. Each report was represented as a word-trajectory graph. Connectedness was measured by number of edges, number of nodes in the largest connected component and number of nodes in the largest strongly connected component. Similarities to random graphs were estimated. All connectedness attributes were combined into a single Disorganization Index weighted by the correlation with the positive and negative syndrome scale negative subscale, and used for classifications. Random-like connectedness was more prevalent among schizophrenia patients (64?×?5% in Control group, p?=?0.0002). Connectedness from two kinds of memory reports (dream and negative image) explained 88% of negative symptoms variance (p?<?0.0001). The Disorganization Index classified low vs. high severity of negative symptoms with 100% accuracy (area under the receiver operating characteristic curve?=?1), and schizophrenia diagnosis with 91.67% accuracy (area under the receiver operating characteristic curve?=?0.85). The index was validated in an independent cohort of chronic psychotic patients and controls (N?=?60) (85% accuracy). Thus, speech disorganization during the first clinical contact correlates tightly with negative symptoms, and is quite discriminative of the schizophrenia diagnosis.
| S-EPMC5441540 | biostudies-literature