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

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. Objectives In 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. Methods NS 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. Results According 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. Conclusions The 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 Interest None Declared

Introduction Network analysis has been used to explore the interplay between psychopathology and functioning in psychosis, but no study has used dedicated statistical techniques to focus on the bridge symptoms connecting these domains. Objectives The current study aims to estimate the network of depressive, negative, and positive symptoms, general psychopathology, and real-world functioning in people with first-episode schizophrenia or schizophreniform disorder, focusing on bridge nodes. Methods Baseline data from the OPTiMiSE trial were analysed. The sample included 446 participants (age 40.0±10.9 years, 70% males). The network was estimated with a Gaussian graphical model (GGM), using scores on individual items of the Positive and Negative Syndrome Scale (PANSS), the Calgary Depression Scale for Schizophrenia (CDSS), and the Personal and Social Performance (PSP) scale. Stability, strength centrality, expected influence (EI), predictability, and bridge centrality statistics were computed. The top 20% scoring nodes on bridge strength were selected as bridge nodes. Results Nodes from different rating scales assessing similar psychopathological and functioning constructs tended to cluster together in the estimated network (Fig. 1). The most central nodes (EI) were Delusions, Emotional Withdrawal, Depression, and Depressed Mood. Bridge nodes included Depression, Conceptual Disorganisation, Active Social Avoidance, Delusions, Stereotyped Thinking, Poor Impulse Control, Guilty Feelings, Unusual Thought Content, and Hostility. Most of the bridge nodes belonged to the general psychopathology subscale of the PANSS. Depression (G6) was the bridge node with the highest value. Image: Conclusions The current study provides novel insights for understanding the complex phenotype of psychotic disorders and the mechanisms underlying the development and maintenance of comorbidity and functional impairment after psychosis onset. Disclosure of Interest None Declared

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. Objectives The 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. Methods A 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. Results Databases 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. Conclusions The 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 Interest None Declared

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. Objectives The 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. Methods A 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. Results Only 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. Conclusions Based 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

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. Objectives The 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. Methods EEG 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. Results The TANOVA interaction effect (group x cue) was significant in the time window between 140.6 and 195.3 msec after cue presentation (p

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. Objectives The 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. Methods Resting-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). Results The 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. Conclusions The 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 Interest None Declared

Introduction Although generally effective in ameliorating the core manifestations of schizophrenia, antipsychotics (APs) may lead to only suboptimal responses or may be associated with a variety of treatment-related adverse events which require additional treatment strategies. Under such clinical circumstances, switching APs represents a rational treatment option. Objectives The present study aimed to identify the variables that predict AP switch and to quantify the frequency of this phenomenon in people with schizophrenia in real-life. Methods A secondary analysis was conducted on the data collected at baseline and at a 4-year follow-up from a large sample of community-dwelling Italian people with schizophrenia. Demographic and clinical variables as well as information about AP treatment were recorded at two time points. Over the 4-year period, 34.9% of the 571 participants switched the AP; in particular, 8.4% of participants switched from first-generation APs (FGAs) to second-generation APs or vice versa, while 8.2% of them switched to clozapine. Results Logistic regression models showed that combination of APs at baseline was negatively associated with AP switch, while treatment with FGAs and the presence of extrapyramidal symptoms at baseline were associated with AP class switch. Conclusions Although the aim of the present study was not to assess predictors of clinical relapse in people with schizophrenia, we might speculate that switching APs represents a surrogate indicator of treatment failure in some patients and could lead into relapse, which is a costly aspect of schizophrenia management in both economic and human terms. The sooner such a negative outcome can be predicted and managed, the sooner the treatment can be optimized to avoid it. Disclosure of Interest None Declared

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. Objectives The 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). Methods The 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. Results At 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

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. Objectives The aim of this study was to investigate the stability of the latent structure of NS in subjects with SCZ. Methods NS 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. Results Results 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). Conclusions The 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 Interest None Declared

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.

AbstractBackgroundDuring 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.