Negative symptoms in schizophrenia.
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ABSTRACT:
SUBMITTER: Mitra S
PROVIDER: S-EPMC5479085 | biostudies-literature | 2016 Jul-Dec
REPOSITORIES: biostudies-literature
Publications
Negative symptoms in schizophrenia.
Mitra Sayantanava S Mahintamani Tathagata T Kavoor Anjana Rao AR Nizamie S Haque SH
Industrial psychiatry journal 20160701 2
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 inve ...[more]
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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: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.
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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.
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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.
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Project description: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.
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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.
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Project description:Negative symptoms occur in several major mental health disorders with undetermined mechanisms and unsatisfactory treatments; identification of their neural correlates might unveil the underlying pathophysiological basis and pinpoint the therapeutic targets. In this study, participants with major depressive disorder (n?=?24), schizophrenia (n?=?22), and healthy controls (n?=?20) were assessed with 10 frequently used negative symptom scales followed by principal component analysis (PCA) of the scores. A linear model with the prominent components identified by PCA was then regressed on gray and white-matter volumes estimated from T1-weighted magnetic resonance imaging. In depressed patients, negative symptoms such as blunted affect, alogia, withdrawal, and cognitive impairment, assessed mostly via clinician-rated scales were inversely associated with gray matter volume in the bilateral cerebellum. In patients with schizophrenia, anhedonia, and avolition evaluated via self-rated scales inversely related to white-matter volume in the left anterior limb of internal capsule/anterior thalamic radiation and positively in the left superior longitudinal fasiculus. The pathophysiological mechanisms underlying negative symptoms might differ between depression and schizophrenia. These results also point to future negative symptom scale development primarily focused on detecting and monitoring the corresponding changes to brain structure or function.
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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.
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Project description:Negative symptoms in schizophrenia are characterized by deficits in normative experiences and expression of emotion, and they are associated with poor social functioning. Negative symptoms relating to deficits in motivation and pleasure may hinder the development of affiliative bonds. The current study used a novel procedure to examine the relation between negative symptoms and the development of social affiliation within a laboratory setting. Fifty-five men (35 controls; 20 with a schizophrenia spectrum disorder) completed three Social Affiliation Enhancement Tasks with an experimenter partner. Self-reported affiliation and affect ratings were assessed before and after the affiliative interaction. Across groups, social affiliation and positive affect increased following the interactive tasks. However, the schizophrenia group reported less positive and more negative affect than controls. Within individuals with schizophrenia, negative symptoms reflecting motivation and pleasure deficits and self-reported social anhedonia were associated with less affiliative feelings of interpersonal closeness and less willingness to interact. Additionally, these self-reported reactions to the interaction partner were significantly related to social functioning in the community. These findings indicate that though individuals with schizophrenia can form affiliative bonds, the extent to which this is possible may be limited by negative symptoms relating to motivation and pleasure. Additional research will be necessary to examine just how these negative symptoms interfere with social affiliation.
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