A new era for the negative symptoms of schizophrenia.

Negative symptoms remain one of the major unmet needs for people with schizophrenia, and the past decade has witnessed a surge in interest in negative symptoms. In this themed issue, we present new concepts of negative symptoms and recent findings on their epidemiology and pathophysiology and on therapeutic options for their management.

Two and five-factor models of negative symptoms in schizophrenia are differentially associated with trait affect, defeatist performance beliefs, and psychosocial functioning.

Recent factor analytic evidence supports both two-factor (motivation and pleasure, MAP; diminished expression, EXP) and five-factor (anhedonia, asociality, avolition, blunted affect, alogia) conceptualizations of negative symptoms. However, it is unclear whether these two conceptualizations of the latent structure of negative symptoms have differential associations with external correlates. The current study evaluated external correlates of the two- and five-factor structures by examining associations with variables known to have critical relations with negative symptoms: trait affect, defeatist performance beliefs, neurocognition, and community-based psychosocial functioning. Participants included a total of 245 outpatients diagnosed with schizophrenia who were rated on the Brief Negative Symptom Scale and completed a battery of additional measures during periods of clinical stability. These additional measures included the Positive and Negative Affect Schedule, Defeatist Performance Beliefs scale, MATRICS Consensus Cognitive Battery, and Level of Function Scale. Pearson correlations indicated differential patterns of associations between the BNSS scores and the external correlates. Support for the two-factor model was indicated by a stronger association of MAP with positive affect and psychosocial functioning, compared to EXP with neurocognition. Significance tests examining a differential magnitude of associations showed that the two-dimension negative symptom structure masked unique correlational relationships among the five negative symptom domains with neurocognition and social/vocational community functioning and captured unique patterns of correlation with trait affect. Support for the five-factor model was shown by a stronger association between Blunted Affect with Attention/Vigilance, and stronger associations between Avolition, Anhedonia, and Asociality with psychosocial functioning. Results offer support for both the two-dimension and five-domain model of negative symptoms as well as a hierarchical two-dimensions-five-domains model of negative symptoms. Findings may have implications for diagnostic criteria and descriptions of the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5), as well as possible treatment targets of negative symptoms.

Aberrant salience correlates with psychotic dimensions in outpatients with schizophrenia spectrum disorders.

BACKGROUND: Aberrant salience is a well-known construct associated with the development and maintenance of psychotic symptoms in schizophrenia. However, only a few studies have investigated aberrance salience as a trait, with no study investigating the association between the five aberrant salience domains and psychotic symptoms. We aimed to explore the role of aberrant salience and its domains on psychotic dimensions in both clinically remitted and non-remitted patients. METHODS: A sample of 102 patients diagnosed with schizophrenia spectrum disorders was divided according to the Positive and Negative Syndrome Scale (PANSS) remission criteria into two groups: remitted and non-remitted. Differences regarding psychotic symptomatology assessed by the PANSS and aberrant salience measured by the Aberrant Salience Inventory (ASI) were explored. Finally, a correlation analysis between the PANSS and the ASI was run. RESULTS: Significantly higher ASI scores were evident among non-remitted patients. Positive symptoms (i.e. delusions, conceptual disorganization, and hallucinatory behaviour) and general psychopathology (i.e. postural mannerisms, unusual thought content) were correlated to the aberrant salience subscales 'sharpening of senses', 'heightened emotionality' and 'heightened cognition' and with the ASI total score. Significant correlations emerged between negative symptoms (blunted affect and social withdrawal) and 'heightened cognition'. Finally, lack of spontaneity of conversation was related to the subscales 'heightened emotionality' and 'heightened cognition', as well as to the ASI total score. CONCLUSIONS: These preliminary results support the hypothesis of an association between aberrant salience and psychotic symptoms in schizophrenia. Further research is needed, especially into the mechanisms underlying salience processing, in addition to social and environmental factors and cognitive variables.

The Associations between COMT and MAO-B Genetic Variants with Negative Symptoms in Patients with Schizophrenia.

Negative symptoms of schizophrenia, including anhedonia, represent a heavy burden on patients and their relatives. These symptoms are associated with cortical hypodopamynergia and impaired striatal dopamine release in response to reward stimuli. Catechol-O-methyltransferase (COMT) and monoamine oxidase type B (MAO-B) degrade dopamine and affect its neurotransmission. The study determined the association between COMT rs4680 and rs4818, MAO-B rs1799836 and rs6651806 polymorphisms, the severity of negative symptoms, and physical and social anhedonia in schizophrenia. Sex-dependent associations were detected in a research sample of 302 patients with schizophrenia. In female patients with schizophrenia, the presence of the G allele or GG genotype of COMT rs4680 and rs4818, as well as GG haplotype rs4818-rs4680, which were all related to higher COMT activity, was associated with an increase in several dimensions of negative symptoms and anhedonia. In male patients with schizophrenia, carriers of the MAO-B rs1799836 A allele, presumably associated with higher MAO-B activity, had a higher severity of alogia, while carriers of the A allele of the MAO-B rs6651806 had a higher severity of negative symptoms. These findings suggest that higher dopamine degradation, associated with COMT and MAO-B genetic variants, is associated with a sex-specific increase in the severity of negative symptoms in schizophrenia patients.

Fronto-temporal connectivity predicts cognitive empathy deficits and experiential negative symptoms in schizophrenia.

Impaired cognitive empathy is a core social cognitive deficit in schizophrenia associated with negative symptoms and social functioning. Cognitive empathy and negative symptoms have also been linked to medial prefrontal and temporal brain networks. While shared behavioral and neural underpinnings are suspected for cognitive empathy and negative symptoms, research is needed to test these hypotheses. In two studies, we evaluated whether resting-state functional connectivity between data-driven networks, or components (referred to as, inter-component connectivity), predicted cognitive empathy and experiential and expressive negative symptoms in schizophrenia subjects. Study 1: We examined associations between cognitive empathy and medial prefrontal and temporal inter-component connectivity at rest using a group-matched schizophrenia and control sample. We then assessed whether inter-component connectivity metrics associated with cognitive empathy were also related to negative symptoms. Study 2: We sought to replicate the connectivity-symptom associations observed in Study 1 using an independent schizophrenia sample. Study 1 results revealed that while the groups did not differ in average inter-component connectivity, a medial-fronto-temporal metric and an orbito-fronto-temporal metric were related to cognitive empathy. Moreover, the medial-fronto-temporal metric was associated with experiential negative symptoms in both schizophrenia samples. These findings support recent models that link social cognition and negative symptoms in schizophrenia. Hum Brain Mapp 38:1111-1124, 2017. © 2016 Wiley Periodicals, Inc.

Thirty years of research on negative symptoms of schizophrenia: A scientometric analysis of hotspots, bursts, and research trends.

Research on negative symptoms of schizophrenia has received renewed interest since the 1980s. A scientometric analysis that objectively maps scientific knowledge, with changes in recent trends, is currently lacking. We searched the Web of Science Core Collection (WOSCC) on December 17, 2021 using relevant keywords. R-bibliometrix and CiteSpace were used to perform the analysis. We retrieved 27,568 references published between 1966 and 2022. An exponential rise in scientific interest was observed, with an average annual growth rate in publications of 16.56% from 1990 to 2010. The co-cited reference network that was retrieved presented 24 different clusters with a well-structured network (Q=0.7921; S=0.9016). Two distinct major research trends were identified: research on the conceptualization and treatment of negative symptoms. The latest trends in research on negative symptoms include evidence synthesis, nonpharmacological treatments, and computational psychiatry. Scientometric analyses provide a useful summary of changes in negative symptom research across time by identifying intellectual turning point papers and emerging trends. These results will be informative for systematic reviews, meta-analyses, and generating novel hypotheses.

Latent Factors of Language Disturbance and Relationships to Quantitative Speech Features.

BACKGROUND AND HYPOTHESIS: Quantitative acoustic and textual measures derived from speech ("speech features") may provide valuable biomarkers for psychiatric disorders, particularly schizophrenia spectrum disorders (SSD). We sought to identify cross-diagnostic latent factors for speech disturbance with relevance for SSD and computational modeling. STUDY DESIGN: Clinical ratings for speech disturbance were generated across 14 items for a cross-diagnostic sample (N = 334), including SSD (n = 90). Speech features were quantified using an automated pipeline for brief recorded samples of free speech. Factor models for the clinical ratings were generated using exploratory factor analysis, then tested with confirmatory factor analysis in the cross-diagnostic and SSD groups. The relationships between factor scores and computational speech features were examined for 202 of the participants. STUDY RESULTS: We found a 3-factor model with a good fit in the cross-diagnostic group and an acceptable fit for the SSD subsample. The model identifies an impaired expressivity factor and 2 interrelated disorganized factors for inefficient and incoherent speech. Incoherent speech was specific to psychosis groups, while inefficient speech and impaired expressivity showed intermediate effects in people with nonpsychotic disorders. Each of the 3 factors had significant and distinct relationships with speech features, which differed for the cross-diagnostic vs SSD groups. CONCLUSIONS: We report a cross-diagnostic 3-factor model for speech disturbance which is supported by good statistical measures, intuitive, applicable to SSD, and relatable to linguistic theories. It provides a valuable framework for understanding speech disturbance and appropriate targets for modeling with quantitative speech features.

Implicit cognitive effort monitoring impairments are associated with expressive negative symptoms in schizophrenia.

Negative symptoms are a strong predictor of functional impairment in schizophrenia (SZ). Unfortunately, mechanisms underlying negative symptoms are poorly understood and available treatments are minimally effective. The current study evaluated the novel hypothesis that negative symptoms are associated with an implicit cognitive effort monitoring impairment that manifests during tasks requiring sustained allocation of cognitive control. Outpatients with SZ (n = 33) and healthy controls (CN; n = 29) completed an adapted Demand Selection Task (DST) in which subjects made choices between pairs of cognitive tasks that were implicitly and then explicitly made discrepant in effort demands. The SZ group demonstrated a reduced probability of avoiding the high effort cognitive task in the implicit choice condition but were able to become effort avoidant when the demands of the task were made explicit. Implicit cognitive effort monitoring deficits were associated with greater severity of the expressivity dimension of negative symptoms, but not the motivation and pleasure dimension. The association between diminished expressivity and implicit cognitive effort monitoring deficits is interpreted in light of a novel cognitive resource depletion theory, whereby individuals with SZ may become less expressive due to difficulty implicitly monitoring ongoing cognitive effort exertion and dynamically adjusting effort expenditure as task demands fluctuate.

Two Factors, Five Factors, or Both? External Validation Studies of Negative Symptom Dimensions in Schizophrenia.

OBJECTIVES: Negative symptom studies frequently use single composite scores as indicators of symptom severity and as primary endpoints in clinical trials. Factor analytic and external validation studies do not support this practice but rather suggest a multidimensional construct. The current study used structural equation modeling (SEM) to compare competing dimensional models of negative symptoms to determine the number of latent dimensions that best capture variance in biological, psychological, and clinical variables known to have associations with negative symptoms. METHODS: Three independent studies (total n = 632) compared unidimensional, two-factor, five-factor, and hierarchical conceptualizations of negative symptoms in relation to cognition, psychopathology, and community functioning (Study 1); trait emotional experience and defeatist performance beliefs (Study 2); and glutamate and gamma-aminobutyric acid levels in the anterior cingulate cortex quantified using proton magnetic resonance spectroscopy (Study 3). RESULTS: SEM favored the five-factor and hierarchical models over the unidimensional and two-factor models regardless of the negative symptom measure or external validator. The five dimensions-anhedonia, asociality, avolition, blunted affect, and alogia-proved vital either as stand-alone domains or as first-order domains influenced by second-order dimensions-motivation and pleasure and emotional expression. The two broader dimensions sometimes masked important associations unique to the five narrower domains. Avolition, anhedonia, and blunted affect showed the most domain-specific associations with external variables across study samples. CONCLUSIONS: Five domains and a hierarchical model reflect the optimal conceptualization of negative symptoms in relation to external variables. Clinical trials should consider using the two dimensions as primary endpoints and the five domains as secondary endpoints.

High-Order Language Processing Difficulties in Patients With Schizophrenia: Cross-linguistic and Cross-cultural Results From the Hindi Version of a Newly Developed Language Test.

Objective: To detect subtle linguistic performance deficits in patients with schizophrenia, a test battery was developed in Hindi vernacular language. Method: It was a replication study of observational, analytical, and case-control design. Total of 86 participants, namely 43 patients with schizophrenia and 43 controls, were recruited into the study. The patients were evaluated by using PANSS (positive and negative symptoms scale for schizophrenia) for recruitment into the study. Participants from the general population were evaluated with GHQ-12 (General Health Questionnaire-12) to be found to fit as healthy controls. Subsequently, the linguistic performance of patients (on HLFT: Hindi linguistic function test) was compared with that of controls. The HLFT battery was designed, containing 3 blocks by using antonyms, synonyms, homonyms, hyperonyms, hyponyms, distractors, and adages. Result: Patients scored significantly less than that of controls in identifying antonyms, distractors, and hyponyms while in identifying homonyms they scored significantly more than that of controls. At block I (antonyms) score of 15.5; at homonym score of 5.5; at hyponym (as in hyponym plus distractor combination) score of 2.5, the sensitivity and specificity for using them as a cutoff to screen for schizophrenia are 60.5% and 67.4%; 86% and 41.9%; 81.4% and 46.5%, respectively. Conclusion: Ambiguity processing of taxonomic representation such as antonymia, homonymia, hypo-/hyperonymia, synonymia, and also understanding of adages might be significantly impaired in patients with schizophrenia. The HLFT battery could be used as a quick and sensitive instrument to detect and quantify the linguistic difficulties of patients with schizophrenia.

Reprint of: A review of negative symptom assessment strategies in youth at clinical high-risk for psychosis.

Studies attempting to deconstruct the heterogeneity of schizophrenia and the attenuated psychosis syndrome consistently find that negative symptoms are a core dimension that is distinct from other aspects of the illness (e.g., positive and disorganized symptoms). Negative symptoms are also highly predictive of poor community-based functional outcomes, suggesting they are a critical treatment target. Unfortunately, pharmacological and psychosocial treatments for negative symptoms have demonstrated limited effectiveness. To address this critical unmet therapeutic need, the NIMH sponsored a consensus development conference to delineate research priorities for the field and stimulate treatment development. A primary conclusion of this meeting was that next-generation negative symptom rating scales should be developed to address methodological and conceptual limitations of existing instruments. Although second-generation rating scales were developed for adults with schizophrenia, progress in this area has lagged behind for youth at clinical-high risk (CHR) for developing psychosis (i.e. those meeting criteria for a prodromal syndrome). Given that negative symptoms are highly predictive of the transition to diagnosable psychotic illness, enhancing our ability to detect negative symptoms in CHR youth is paramount. The current paper discusses conceptual and methodological limitations inherent to existing scales that assess negative symptoms in CHR youth. The theoretical and clinical implications of these limitations are evaluated. It is concluded that new scales specifically designed to assess negative symptoms in CHR youth are needed to accurately chart mental illness trajectories and determine when, where, and how to intervene. Recent efforts to develop next-generation measures designed specifically for CHR youth to meet this urgent need in the field are discussed. These new approaches offer significant progress for addressing issues inherent to earlier scales.

The Latent Structure of Negative Symptoms in Individuals With Attenuated Psychosis Syndrome and Early Psychosis: Support for the 5 Consensus Domains.

Negative symptoms are prevalent in the prodromal and first-episode phases of psychosis and highly predictive of poor clinical outcomes (eg, liability for conversion and functioning). However, the latent structure of negative symptoms is unclear in the early phases of illness. Determining the latent structure of negative symptoms in early psychosis (EP) is of critical importance for early identification, prevention, and treatment efforts. In the current study, confirmatory factor analysis was used to evaluate latent structure in relation to 4 theoretically derived models: 1. a 1-factor model, 2. a 2-factor model with expression (EXP) and motivation and pleasure (MAP) factors, 3. a 5-factor model with separate factors for the 5 National Institute of Mental Health (NIMH) consensus development conference domains (blunted affect, alogia, anhedonia, avolition, and asociality), and 4. a hierarchical model with 2 second-order factors reflecting EXP and MAP, as well as 5 first-order factors reflecting the 5 consensus domains. Participants included 164 individuals at clinical high risk (CHR) who met the criteria for a prodromal syndrome and 377 EP patients who were rated on the Brief Negative Symptom Scale. Results indicated that the 1- and 2-factor models provided poor fit for the data. The 5-factor and hierarchical models provided excellent fit, with the 5-factor model outperforming the hierarchical model. These findings suggest that similar to the chronic phase of schizophrenia, the latent structure of negative symptom is best conceptualized in relation to the 5 consensus domains in the CHR and EP populations. Implications for early identification, prevention, and treatment are discussed.

Deconstructing Negative Symptoms in Individuals at Clinical High-Risk for Psychosis: Evidence for Volitional and Diminished Emotionality Subgroups That Predict Clinical Presentation and Functional Outcome.

Negative symptoms are characteristic of schizophrenia and closely linked to numerous outcomes. A body of work has sought to identify homogenous negative symptom subgroups-a strategy that can promote mechanistic understanding and precision medicine. However, our knowledge of negative symptom subgroups among individuals at clinical high-risk (CHR) for psychosis is limited. Here, we investigated distinct negative symptom profiles in a large CHR sample (N = 244) using a cluster analysis approach. Subgroups were compared on external validators that are (1) commonly observed in the schizophrenia literature and/or (2) may be particularly relevant for CHR individuals, informing early prevention and prediction. We observed 4 distinct negative symptom subgroups, including individuals with (1) lower symptom severity, (2) deficits in emotion, (3) impairments in volition, and (4) global elevations. Analyses of external validators suggested a pattern in which individuals with global impairments and volitional deficits exhibited more clinical pathology. Furthermore, the Volition group endorsed more disorganized, anxious, and depressive symptoms and impairments in functioning compared to the Emotion group. These data suggest there are unique negative symptom profiles in CHR individuals, converging with studies in schizophrenia indicating motivational deficits may be central to this symptom dimension. Furthermore, observed differences in CHR relevant external validators may help to inform early identification and treatment efforts.

A review of negative symptom assessment strategies in youth at clinical high-risk for psychosis.

Studies attempting to deconstruct the heterogeneity of schizophrenia and the attenuated psychosis syndrome consistently find that negative symptoms are a core dimension that is distinct from other aspects of the illness (e.g., positive and disorganized symptoms). Negative symptoms are also highly predictive of poor community-based functional outcomes, suggesting they are a critical treatment target. Unfortunately, pharmacological and psychosocial treatments for negative symptoms have demonstrated limited effectiveness. To address this critical unmet therapeutic need, the NIMH sponsored a consensus development conference to delineate research priorities for the field and stimulate treatment development. A primary conclusion of this meeting was that next-generation negative symptom rating scales should be developed to address methodological and conceptual limitations of existing instruments. Although second-generation rating scales were developed for adults with schizophrenia, progress in this area has lagged behind for youth at clinical-high risk (CHR) for developing psychosis (i.e. those meeting criteria for a prodromal syndrome). Given that negative symptoms are highly predictive of the transition to diagnosable psychotic illness, enhancing our ability to detect negative symptoms in CHR youth is paramount. The current paper discusses conceptual and methodological limitations inherent to existing scales that assess negative symptoms in CHR youth. The theoretical and clinical implications of these limitations are evaluated. It is concluded that new scales specifically designed to assess negative symptoms in CHR youth are needed to accurately chart mental illness trajectories and determine when, where, and how to intervene. Recent efforts to develop next-generation measures designed specifically for CHR youth to meet this urgent need in the field are discussed. These new approaches offer significant progress for addressing issues inherent to earlier scales.

Network Analysis Reveals the Latent Structure of Negative Symptoms in Schizophrenia.

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.

Cross-cultural Validation of the 5-Factor Structure of Negative Symptoms in Schizophrenia.

OBJECTIVE: Negative 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. METHOD: Participants 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. RESULTS: Models 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. CONCLUSIONS: Findings 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.

Thought, language, and communication deficits and association with everyday functional outcomes among community-dwelling middle-aged and older adults with schizophrenia.

Older adults with schizophrenia experience poorer community integration and social functioning compared to same-age peers with no mental health disorders; these individuals are at elevated risk for functional decline and early institutionalization in long-term care facilities. Deficits in thought, language, and communication (TLC; that is, thought disorder and alogia) are core features of schizophrenia and may worsen with age; however, little research focuses on the functional sequelae of these impairments among older adults with schizophrenia. The present study aimed to examine the relationships among age, TLC deficits, and functional outcomes in a sample of community-dwelling middle-aged and older adults with schizophrenia (N = 245; ages 40-85). Participants completed assessments of symptoms, neurocognition, TLC deficits, and functional outcomes. Two different categories of TLC deficits were examined: verbal underproductivity (i.e., alogia) and disconnected speech. Regression analyses, controlling for gender, age, Veteran status, smoking status, cognitive impairment, and symptom severity, found that disconnected speech predicted occupational functioning, while verbal underproductivity predicted capacity to communicate skillfully in semi-structured social situations, as well as community functioning across interpersonal, occupational, and everyday living domains. Exploratory mediation analyses found significant indirect effects of age, through TLC deficits, on certain functional outcomes. Targeted training to improve TLC deficits, especially verbal underproductivity, among older adults with schizophrenia could have downstream effects on community functioning, improving outcomes for a vulnerable group.

A Transdiagnostic Review of Negative Symptom Phenomenology and Etiology.

In the DSM5, negative symptoms are 1 of the 5 core dimensions of psychopathology evaluated for schizophrenia. However, negative symptoms are not pathognomonic-they are also part of the diagnostic criteria for other schizophrenia-spectrum disorders, disorders that sometimes have comorbid psychosis, diagnoses not in the schizophrenia-spectrum, and the general "nonclinical" population. Although etiological models of negative symptoms have been developed for chronic schizophrenia, there has been little attention given to whether these models have transdiagnostic applicability. In the current review, we examine areas of commonality and divergence in the clinical presentation and etiology of negative symptoms across diagnostic categories. It was concluded that negative symptoms are relatively frequent across diagnostic categories, but individual disorders may differ in whether their negative symptoms are persistent/transient or primary/secondary. Evidence for separate dimensions of volitional and expressive symptoms exists, and there may be multiple mechanistic pathways to the same symptom phenomenon among DSM-5 disorders within and outside the schizophrenia-spectrum (ie, equifinality). Evidence for a novel transdiagnostic etiological model is presented based on the Research Domain Criteria (RDoC) constructs, which proposes the existence of 2 such pathways-a hedonic pathway and a cognitive pathway-that can both lead to expressive or volitional symptoms. To facilitate treatment breakthroughs, future transdiagnostic studies on negative symptoms are warranted that explore mechanisms underlying volitional and expressive pathology.

The current conceptualization of negative symptoms in schizophrenia.

Negative symptoms have long been conceptualized as a core aspect of schizophrenia. They play a key role in the functional outcome of the disorder, and their management represents a significant unmet need. Improvements in definition, characterization, assessment instruments and experimental models are needed in order to foster research aimed at developing effective interventions. A consensus has recently been reached on the following aspects: a) five constructs should be considered as negative symptoms, i.e. blunted affect, alogia, anhedonia, asociality and avolition; b) for each construct, symptoms due to identifiable factors, such as medication effects, psychotic symptoms or depression, should be distinguished from those regarded as primary; c) the five constructs cluster in two factors, one including blunted affect and alogia and the other consisting of anhedonia, avolition and asociality. In this paper, for each construct, we report the current definition; highlight differences among the main assessment instruments; illustrate quantitative measures, if available, and their relationship with the evaluations based on rating scales; and describe correlates as well as experimental models. We conclude that: a) the assessment of the negative symptom dimension has recently improved, but even current expert consensus-based instruments diverge on several aspects; b) the use of objective measures might contribute to overcome uncertainties about the reliability of rating scales, but these measures require further investigation and validation; c) the boundaries with other illness components, in particular neurocognition and social cognition, are not well defined; and d) without further reducing the heterogeneity within the negative symptom dimension, attempts to develop successful interventions are likely to lead to great efforts paid back by small rewards.

Negative symptoms in bipolar disorder and schizophrenia: A psychometric evaluation of the brief negative symptom scale across diagnostic categories.

Past studies have demonstrated that the Brief Negative Symptom Scale (BNSS) has excellent psychometric properties in patients with schizophrenia. In the current study, we extended this literature by examining psychometric properties of the BNSS in outpatients diagnosed with bipolar disorder (n=46), outpatients with schizophrenia (n=50), and healthy controls (n=27). Participants completed neuropsychological testing and a clinical interview designed to assess negative, positive, disorganized, mood, and general psychiatric symptoms. Results indicated differences among the 3 groups in the severity of all BNSS items, with SZ and BD scoring higher than CN; however, SZ and BD only differed on blunted affect and alogia items, not anhedonia, avolition, or asociality. BD patients with a history of psychosis did not differ from those without a history of psychosis on negative symptom severity. The BNSS had excellent internal consistency in SZ, BD, and CN groups. Good convergent and discriminant validity was apparent in SZ and BD groups, as indicated by relationships between the BNSS and other clinical rating scales. These findings support the validity of the BNSS in broadly defined serious mental illness populations.