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Resting-state brain activity dysfunctions in schizophrenia and their associations with negative symptom domains
- P. Pezzella, G. M. Giordano, L. Fazio, L. Giuliani, A. Mucci, P. Bucci, M. Amore, P. Rocca, A. Rossi, A. Perrottelli, E. Caporusso, A. Bertolino, S. Galderisi, M. Maj
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S550-S551
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Introduction
Negative symptoms represent a fundamental aspect of schizophrenia: they have a substantial impact on patients’ real-life functioning and do not respond satisfactorily to currently available treatments. Therefore, a better understanding of the pathophysiological mechanisms underlying these symptoms could favor the development of new treatments.
To date, the most validated pathophysiological hypothesis indicates an association between the Motivational domain (consisting of avolition, anhedonia and asociality) and alterations in the neuronal circuits involved in motivation. The Expressive Deficit domain (consisting of blunted affect and alogia) would be subtended by widespread alterations of cortical connectivity and associated with impaired neurocognition, social cognition, and the presence of neurological soft signs.
ObjectivesThe aim of the present study is to examine the neurobiological correlates of the two domains of negative symptoms, starting from the brain areas that have been most commonly found in the literature to be associated with negative symptoms.
MethodsResting-state (rs) fMRI data were acquired in 62 subjects with schizophrenia (SZ) and 46 healthy controls (HC). The two negative symptom domains were assessed using the Brief Negative Symptom Scale. In addition, the following assessment tools were used: the Positive and Negative Syndrome Scale for the assessment of positive symptoms and disorganization, the Calgary Depression Scale for Schizophrenia for depression and the St. Hans Rating Scale for extrapyramidal symptoms. The study of the possible relationships between rs-brain activity and the negative symptoms domains was conducted through partial correlations, checking for possible confounding factors (positive, depressive, extrapyramidal symptoms and disorganization).
ResultsThe SZ, compared to the HC, showed higher rs-brain activity of the right inferior parietal lobule and of the right temporoparietal junction and lower rs-brain activity of the right dorsolateral prefrontal cortex, bilateral anterior dorsal cingulate cortex, bilateral ventral caudate and bilateral dorsal caudate. Furthermore, in the group of patients, the rs-brain activity of the left ventral caudate showed a moderate negative correlation with the Expressive deficit domain (r = -0.401; p = 0.003), but not with the Motivational domain.
ConclusionsThe results of the present study, in line with the literature, demonstrated how the two domains of negative symptomatology are subtended by different pathophysiological mechanisms. Given the role played by the ventral caudate in neurocognitive processes, these results are in line with the hypothesis that Expressive deficit may have a common etiopathogenesis with cognitive deficits. A better understanding of the neurobiology of negative symptoms could foster the development of innovative treatment strategies targeting the two negative symptom domains.
Disclosure of InterestNone Declared
The Brief Negative Symptom Scale: external validation of symptom domains with clinical, cognitive and functioning-related variables in subjects with schizophrenia
- G. M. Giordano, A. Mucci, P. Rucci, F. Sanmarchi, E. Caporusso, L. Giuliani, A. Perrottelli, P. Pezzella, P. Bucci, P. Rocca, A. Rossi, A. Bertolino, S. Galderisi, M. Maj
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S264-S265
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Introduction
Negative symptoms (NS) represent a heterogeneous construct of schizophrenia, whose conceptualization is still to be clarified. In the last decade, the conceptualization model that has received the most support from the literature has described 2 NS domains: the expressive deficit (EXP), which includes blunted affect and alogia, and the motivational deficit (MAP), which includes avolition, asociality, and anhedonia. However, different confirmatory factor-analytic studies suggest that the bi-dimensional model may not capture the complexity of this construct, which could be better defined by a 5-factor model (5 individual negative symptoms) or a hierarchical model (5 individual negative symptoms as first-order factors, and the 2 domains, MAP and EXP domains, as second-order factors). However, to our knowledge, no study has investigated associations between negative symptom models with social cognition and functional capacity, which are largely documented to correlate with negative symptoms, nor the associations with external validators over time, looking at the potential stability of negative symptom models validity through the course of the illness.
ObjectivesIn the light of this observations, we investigated, the external validity of the five-factor model and the hierarchical model of the BNSS in subjects with schizophrenia, looking at associations with cognition, social cognition, functioning and functional capacity at baseline and at four years follow-up.
MethodsNS were assessed in 612 subjects with schizophrenia using the Brief Negative Symptom Scale at the baseline and after 4-year follow-up. State of the art assessment instruments were used to assess cognitive and functioning related variables. Structural equation models (SEM) that included the NS models and 4 external variables were used to our aim.
ResultsAccording to recent multicenter studies, our results confirmed the validity of the 5-factor- and the hierarchical-model of negative symptoms. In particular, these 2 models proved to be equivalent in terms of fit to the data at baseline and follow-up. As regard to the relationship of the two BNSS models with external variables, we found that there was a similar pattern of associations at the two time points despite minor variations.
ConclusionsThe five factor and the hierarchical models provide an optimal conceptualization of negative symptoms in relation to external variables. The similar pattern of associations with external variables of the two models at the two time points despite minor variations, suggests that the simple and widely used 5-factor solution provides the best balance between parsimony and granularity to summarize BNSS structure. This data is of important relevance with consequent implications in the study of pathophysiological mechanisms and the development of targeted treatments for NS.
Disclosure of InterestNone Declared
Investigating the prevalence of mental disorders and related risk factors in refugees and asylum seekers in Campania
- L. Giuliani, D. Palumbo, G. M. Giordano, A. Perrottelli, P. Pezzella, E. Caporusso, P. Bucci, G. Corrivetti, G. Storti, F. Piras, R. Bracalenti, A. Mucci, S. Galderisi
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S282-S283
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Introduction
In recent years the increasing presence of refugees and asylum seekers displaced from their country of origin, determined significant social, economic, humanitarian and public health implications in host nations. Advancing the knowledge on factors contributing to these implications, could foster the implementation of new public-health plans for these population. As a matter of fact, to date, the rates of mental disorders in these population are uncertain due to the high variability of methods used in the studies on topic, and of risk and protective factors analyzed. The most replicated finding is the high prevalence of Post-Traumatic Stress Disorder (PTSD) and depression in refugees and asylum seekers as compared to the population of host countries.
ObjectivesThe aim of the present study was to investigate the needs for mental health prevention, care and rehabilitation of adult refugees and asylum seekers in Italy, performing a multidisciplinary evaluation of migrants who were guests in two refugees’ centers in Campania (Salerno and Avellino).
MethodsThe Mini-International Neuropsychiatric Interview (MINI) was assessed in 303 migrants, in order to evaluate the presence or not of a psychiatric diagnosis. Analysis of variance (ANOVA) was used to investigate differences between migrants with a mental disorder vs migrants without a mental disorder in terms of cognitive functions, depressive and anxiety symptoms, traumatic events and pre-migration risk factors. Person’s correlation was performed to investigate relationships between the Hopkins Symptom Checklist-25 (HSCL-t25) psychopathological index with all the other above-mentioned variables. Logistic regression was used to evaluate factors associated to the presence of a current mental disorder.
ResultsAt least one mental disorder was found in 90 subjects (29.7% of the sample). Most prevalent diagnoses were major depressive disorder, lifetime panic disorder, PTSD, and generalized anxiety disorder. People with at least one psychiatric illness showed impaired global (F=6.62; p=.011) and social (F=8.22; p=.004) cognition, higher trauma levels (F=70.59; p<.0001) and more severe anxiety and depressive symptoms (F=61.84; p<.0001) compared to healthy migrants. Only trauma levels significantly correlated with HSCL-t25 psychopathological index. Trauma levels, global cognition, occupation, and migration status were associated to the presence of a current mental disorder.
ConclusionsThe results of the present study demonstrated that almost 1/3 of the guests of refugee centers in Campania have a mental disorder. The identification of risk factors associated to the onset of mental disorder and to severity of psychopathology in refugees and asylum seekers, may contribute to plan preventive and early psychiatric care in this population.
Disclosure of InterestNone Declared
The structure stability of negative symptoms: longitudinal network analysis of the Brief Negative Symptom Scale in subjects with schizophrenia
- E. Caporusso, G. M. Giordano, A. Mucci, P. Rucci, F. Sanmarchi, L. Giuliani, A. Perrottelli, P. Pezzella, P. Bucci, P. Rocca, A. Rossi, A. Bertolino, S. Galderisi, M. Maj
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S259-S260
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Introduction
Negative symptoms (NS) represent an unmet need of treatment in schizophrenia (SCZ). As a result, these symptoms pose a significant burden on patients, their families, and the health care system. In the last decade, the conceptualization model that has received the most support from the literature has described 2 domains of NS: the expressive deficit (EXP), which includes blunted affect and alogia, and the motivational deficit (MAP), which includes avolition, asociality, and anhedonia. However, different confirmatory factor-analytic studies suggest that the bi-dimensional model may not capture the complexity of this construct, which could be better defined by the 5-factor model. To date no study exploiting innovative tools and state of the art assessment instruments has yet been conducted to evaluate the NS structure stability over time.
ObjectivesThe aim of this study was to investigate the stability of the latent structure of NS in subjects with SCZ.
MethodsNS were assessed in 612 subjects with SCZ using the Brief Negative Symptom Scale (BNSS) at the baseline and after 4-year follow-up. A network invariance analysis was conducted for the data collected longitudinally.
ResultsResults showed that the BNSS’ items aggregated to form 5 distinct domains (avolition, asociality, blunted affect, alogia and anhedonia). The result of the network invariance test indicated that the network structure remained unchanged over time (network invariance test = 0.13; p = 0.169) while its overall strength decreased significantly (6.28 baseline, 5.79 at follow-up; global strength invariance test = 0.48; p = 0.016).
ConclusionsThe results of this study show how the construct of NS can be better explained by the 5 individual negative symptoms and that this model is almost stable over time. Therefore the 2-dimensional model may be insufficient to describe the characteristics of NS. This data is of important relevance with consequent implications in the study of pathophysiological mechanisms and the development of targeted treatments for NS.
Disclosure of InterestNone Declared
Association between cognitive deficits and negative symptoms: a systematic review of the literature
- A. Melillo, G. M. Giordano, E. Caporusso, F. Tomassini, A. Perrottelli, L. Giuliani, P. Pezzella, N. Sansone, A. Mucci, S. Galderisi
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- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S1046-S1047
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Introduction
In patients with schizophrenia, numerous studies have shown a relationship between negative symptoms and cognitive deficits (both neurocognition and social cognition deficits) and a similar impact of these domains on different clinical features such as onset, course and prognostic relevance. However, this relationship is still today subject of scientific debate.
ObjectivesThe aim of the present study is to conduct a systematic review of the literature on data concerning the relationships between neurocognition and social cognition deficits and the two different domains of negative symptoms ̶ avolition-apathy and expressive deficit.
MethodsA systematic review of the literature was carried out following PRISMA guidelines and examining articles in English published in the last fifteen years (2007 - March 2022) using three different databases (Pubmed, Scopus and PsychINFO). The included studies involved subjects with one of the following diagnoses: high risk of psychosis, first episode of psychosis, or chronic schizophrenia. Other inclusion criteria of the reviewed studies included: evaluation of at least one neurocognitive or social cognition domain and at least one negative symptom using standardized scales; analysis of the relationship between at least one neurocognitive or social cognition domain and a negative symptom.
ResultsDatabases search produced 8497 results. After title and abstract screening, 395 articles were selected, of which 103 met inclusion criteria. The analysis of retrieved data is still ongoing. Preliminary evidence highlighted: a correlation between social cognition and negative symptoms, in particular with the “expressive deficit” domain; a positive correlation between the severity of negative symptoms and that of neurocognitive deficits (in particular with the “processing speed” domain); an association of verbal working memory deficits with alogia and anhedonia.
ConclusionsThe study of the relationship between negative symptoms, neurocognitive deficits and social cognition could contribute to the understanding of the aetiology of psychotic disorders and therefore to the identification of therapies for the improvement of overall functioning and quality of life. The studies analysed so far show some interesting associations between cognition and negative symptoms, but the presence of often inconsistent results, partially attributable to the different conceptualizations of the various domains of negative symptoms adopted, hinders the generalization of the results.
Disclosure of InterestNone Declared
Cognitive impairment after post-acute COVID-19 infection: a systematic review of the literature
- N. Sansone, P. Pezzella, A. Perrottelli, G. M. Giordano, E. Caporusso, L. Giuliani, P. Bucci, A. Mucci, S. Galderisi
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S121-S122
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Introduction
After coronavirus disease 2019 (COVID-19) infection, many individuals reported neurological and psychiatric sequelae, including cognitive impairment, even several months after the acute infection.
ObjectivesThe present study aims to provide a critical overview of the literature on the relationships between post-acute COVID-19 infection and cognitive impairment, highlighting limitations and confounding factors.
MethodsA systematic search of articles published from January 1st, 2020, to July 1st, 2022 was performed in Pubmed/Medline. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
ResultsOnly studies using validated instruments for the assessment of cognitive impairment were included. Out of 5478 screened records, 72 studies met inclusion criteria. Time of patients’ assessment varied from 4 weeks to 12 months after the infection. The available evidence revealed the presence of impairment in executive functions, attention and memory in subjects recovered from COVID-19. However, several limitations of the literature reviewed should be highlighted: most studies were performed on small samples, not stratified by severity of disease and age, used a cross-sectional or a short-term longitudinal design, and provided a limited assessment of the different cognitive domains. Few studies investigated neurobiological correlates of cognitive deficits in individuals recovered from COVID-19.
ConclusionsBased on the literature reviewed, it is difficult, to date, to draw conclusions about the relationships between COVID-19 infection and cognitive impairment. Therefore, further studies with an adequate methodological design are needed in order to better understand these relationships, identify neurobiological correlates of COVID-related cognitive deficits and evaluate their course over time. Enhancing the knowledge on this topic could favor the development of effective therapeutic strategies for cognitive deficits in individuals recovered from COVID-19.
Disclosure of InterestNone Declared
Electrophysiological correlates of reward anticipation in subjects with schizophrenia using topographic analysis of variance (TANOVA) – an ERP study
- A. Perrottelli, T. Koenig, L. Giuliani, P. Pezzella, E. Caporusso, G. M. Giordano, A. Mucci
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S374-S375
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Introduction
The neurobiological underpinnings of negative symptoms in schizophrenia remain unclear. Previous studies have revealed that in schizophrenia, the anticipatory component of the hedonic experience (anticipatory anhedonia, failure to anticipate reward or pleasurable experiences) is more markedly impaired than the consummatory aspect of pleasure (consummatory anhedonia, in the moment experience of pleasure during pleasurable situations). Several neuroimaging focused on reward prediction deficit have shown dysfunctions in the neuronal circuits that sustain these processes in patients, but findings have not been consistent.
ObjectivesThe current study aimed at investigating the impairment of reward anticipation in subjects with schizophrenia (SCZ) during the “Monetary Incentive Delay task” (MID task), employing the topographic analysis of event-related potentials (ERPs) with EEG recordings. Furthermore, the associations with negative symptoms and anticipatory and consummatory hedonic experience were investigated.
MethodsEEG data were recorded in thirty SCZ and twenty-three matched HC, during the MID task in which reward and loss cues (incentive cues of positive and negative value) of different magnitude, as well as neutral cues were presented. Anticipation and experience of pleasure were measured by the Temporal Experience of Pleasure Scale (TEPS), while negative symptom dimensions by the Schedule for the Deficit Syndrome (SDS). For the EEG data analysis, the topographic analysis of variance (TANOVA) that uses the global field power of difference maps was used to evaluate between-group differences in scalp topography. Correlation analyses between hedonic experience, negative symptoms and ERPs were performed.
ResultsThe TANOVA interaction effect (group x cue) was significant in the time window between 140.6 and 195.3 msec after cue presentation (p<.05). Post-hoc analysis showed that significant differences in topography were observed for the reward condition (p=.0006) but not for the loss one (p=.6732) between SCZ and HC. Finally, a significant correlation (p<.01) between t-maps values obtained in the same time-frame and the anticipation of pleasure scores was detected, while no significant correlations were found with the experience of pleasure scores or the severity negative symptom.
ConclusionsSCZ are unable to integrate the incentive magnitude and reward value of future events in the context of their ongoing task. Topographic abnormalities in ERP could be traced already during early stages of reward processing and were associated with anticipation of pleasure, but not with the experience of pleasure or the avolition, suggesting that these constructs might be partially separate.
Disclosure of InterestNone Declared
Resting-state functional connectivity of the ventral tegmental area and negative symptom domains in subjects with schizophrenia
- P. Pezzella, G.M. Giordano, A. Perrottelli, G. Cascino, F. Marciello, G. Blasi, L. Fazio, A. Mucci, S. Galderisi
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- European Psychiatry / Volume 64 / Issue S1 / April 2021
- Published online by Cambridge University Press:
- 13 August 2021, pp. S542-S543
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Introduction
Negative symptoms (NS) represent a core aspect of schizophrenia with a huge impact on real life functioning. Dysfunctions within the dopaminergic cortico-striatal circuits have been documented in subjects with schizophrenia (SCZ) and hypothesized as possible neurobiological mechanisms underlying some domains of NS.
ObjectivesWe investigated relationships between the resting-state functional connectivity (RS-FC) of the ventro-tegmental area (VTA) and NS.
MethodsResting-state fMRI data were recorded in 35 SCZ, recruited within the Italian Network for Research on Psychoses. We performed partial correlations between RS-FC and NS (evaluated with the Brief Negative Symptom Scale) controlling for possible sources of secondary negative symptoms.
ResultsWe found that the experiential domain correlated with the RS-FC of the VTA with the left ventro-lateral prefrontal cortex (lVLPFC) (r=0.372, p=0.039), while the Expressive deficit domain correlated with the RS-FC of the VTA with the left dorso-lateral prefrontal cortex (lDLPFC) (r= 0.470, p .008). Looking at subdomains, only the avolition (r= 0.418, p=0.019) and the blunted affect (r= 0.465, p=.008) showed the same correlations of the domains to which they belong.
ConclusionsAccording to our findings, separate dysfunctional neuronal circuits could underpin distinct negative symptom subdomains. A better understanding of neurobiological dysfunctions underlying NS could help to design new treatments, targeting different NS subdomains.
EPA guidance on treatment of negative symptoms in schizophrenia
- Part of
- S. Galderisi, S. Kaiser, I. Bitter, M. Nordentoft, A. Mucci, M. Sabé, G. M. Giordano, M. Ø. Nielsen, L. B. Glenthøj, P. Pezzella, P. Falkai, S. Dollfus, W. Gaebel
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- European Psychiatry / Volume 64 / Issue 1 / 2021
- Published online by Cambridge University Press:
- 17 March 2021, e21
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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.
EPA guidance on assessment of negative symptoms in schizophrenia
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- S. Galderisi, A. Mucci, S. Dollfus, M. Nordentoft, P. Falkai, S. Kaiser, G. M. Giordano, A. Vandevelde, M. Ø. Nielsen, L. B. Glenthøj, M. Sabé, P. Pezzella, I. Bitter, W. Gaebel
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- Journal:
- European Psychiatry / Volume 64 / Issue 1 / 2021
- Published online by Cambridge University Press:
- 18 February 2021, e23
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Background
During 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.