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.

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.

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).

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.

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.

None Declared

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.

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.

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.

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.

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.

None Declared

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.

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).

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.

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<.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.

The 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.

None Declared

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.

The aim of this study was to investigate the stability of the latent structure of NS in subjects with SCZ.

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 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).

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.

None Declared

After coronavirus disease 2019 (COVID-19) infection, many individuals reported neurological and psychiatric sequelae, including cognitive impairment, even several months after the acute infection.

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.

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.

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.

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.

None Declared

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.

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.

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.

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.

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.

None Declared

An extensive literature regarding gender differences relevant to several aspects of schizophrenia is nowadays available. It includes some robust findings as well as some inconsistencies. The identification of gender differences and the understanding of their explanations may help to clarify the underlying etiopathogenetic mechanisms of specific aspects of the disorder.

The present study aimed at investigating gender differences on premorbid, clinical, cognitive and outcome indices, as well as their impact on recovery, in a large sample of patients with schizophrenia recruited within the multicenter study of the Italian Network for Research on Psychoses.

State-of-the-art instruments were used to assess the investigated domains. Group comparisons between male and female patients were performed on all considered indices. The associations of premorbid, clinical and cognitive indices with recovery in the two patient groups were investigated by means of multiple regressions.

Males with respect to females had a worse premorbid adjustment – limited to the academic dimension – an earlier age of onset, a higher frequency of history of substance and alcohol abuse, more severe negative symptoms (both avolition and expressive deficit), positive symptoms and impairment of social cognition. No gender difference was observed in neurocognition nor in the rates of recovery.

Although males showed some disadvantages in the clinical picture, this was not translated into a worse outcome. This finding may be related to the complex interplay of several factors acting as predictors or mediators of outcome.

No significant relationships.

Cognitive deficits are considered a key feature of schizophrenia due to their substantial influence on the psychosocial outcome of subjects affected by this disorder. Several studies showed that moderate to severe cognitive impairments, including dysfunctions of social cognition, are already present during the early phases of the illness, in subjects with first-episode psychosis (FEPs). Psychosocial interventions, such as social skill training (SST), could therefore be implemented already upon occurrence of the first episode of psychosis to improve the overall functional outcome of schizophrenia, which represents to date an unmet need in the care of these patients.

The study aims to evaluate the use of SST to enhance social skills and real-life functioning in FEPs.

The sample included 7 FEPs (age between 15 and 40). The SST intervention included 30 sessions lasting 2 hours and delivered twice a week. Psychopathology, neurocognition, real life functioning, functional capacity and social cognition were assessed at baseline ad after training. Paired samples t-tests were performed to evaluate the effects of the intervention. All subjects were treated with second generation antipsychotics.

Significant improvements were observed in negative symptoms, social cognition, problem solving skills, as well as in global functioning (all p<0.05). Within real-life functioning, the improvement was greater for the domain of interpersonal relationships.

These preliminary findings suggest that SST might complement pharmacological treatment in FEPs to improve functional outcome in these subjects. Further studies with a higher sample size and a longer follow-up are required in order to confirm the present results.

Prof Mucci has been a consultant and/or advisor to or has received honoraria from Gedeon Richter Bulgaria, Janssen Pharmaceuticals, Lundbeck, Otsuka, Pfizer and Pierre Fabre.

Prof. Mucci has been a consultant and/or advisor to or has received honoraria from Gedeon Richter Bulgaria, Janssen Pharmaceuticals, Lundbeck, Otsuka, Pfizer and Pierre Fabre.

Social cognition and skill deficits have been largely documented in subjects with schizophrenia (SCZs), and have a strong influence on the functional outcome of these subjects. Different behavioural interventions have been developed to target and improve social skills in SCZs. For instance, the Social Skills Training (SST) focuses on improving communication skills and assertiveness to facilitate disease management, independent living and real-life functioning of SCZs. SST seems also to have an impact on negative symptoms and social cognition.

The study aims to evaluate the effectiveness of SST in improving social cognition and negative symptoms in SCZs.

The sample included 8 chronic SCZs (age between 18 and 60), who completed 6 months of SST. The intervention consisted of two weekly group sessions of 2 hours each. We assessed psychopathology, neurocognition, real-life functioning, functional capacity and social cognition at baseline and after training. Paired samples t-tests were performed to evaluate the differences of the variables considered after completing the treatment.

Significant improvements in negative symptoms (p<.05), social cognition (p<.05), functional capacity (p<.001), activities of daily living (p<.001) and interpersonal relationships (p<.011) were found.

The present findings suggest that SST might ameliorate social cognition and negative symptoms which are generally not influenced by antipsychotic treatment. The integration of pharmacological and SST interventions might have an impact on major determinants of poor real-life functioning in SCZs.

Symptomatic remission is increasingly perceived as a realistic objective of pharmacological treatment in patients with schizophrenia (2). However the relationships between symptomatic remission, as defined by standardized criteria, and functional outcome remain controversial. In the present study, we designed a one-year follow-up of clinically stable patients with schizophrenia and examined the relationships of clinical remission with several indices of psychosocial functioning.

Thirty-six patients with schizophrenia were included. All the evaluations were carried out both at baseline (T0) and after a one-year follow-up (T12). The categorization in psychosocial remission/non-remission was done by means of the Psychosocial Remission in Schizophrenia (PSRS) scale.

Both at T0 and at T12, R showed, with respect to NR, a better social functioning and a better quality of life. Correlation analysis revealed that the better the psychosocial functioning, the lower the scores on all psychopathological dimensions, except “anxiety/depression” and “hostility” at T0 as well as “anxiety/depression” at T12. At T0, 65% of R resulted also in psychosocial remission; at T12, this percentage reached 90%.

Our findings suggest that symptomatic remission in schizophrenia is associated to functional outcome in the majority of cases, especially when both symptomatic and chronological criteria are met.

Cognitive impairment in patients with eating disorders was reported by the majority of studies addressing this issue. However, heterogeneous patterns of cognitive dysfunctions were observed and, in a minority of studies, no impairment was found. The present study was aimed to define the pattern of neurocognitive impairment in a large sample of bulimia nervosa (BN) patients and to demonstrate that neuroendocrine, personality and clinical characteristics influence neurocognitive performance in BN.

Attention, executive control, conditional and incidental learning were evaluated in 83 untreated female patients with BN and 77 healthy controls. Cortisol and 17β-estradiol plasma levels were assessed. Cloninger's Temperament and Character Inventory-Revised (TCI-R), the Eating Disorder Inventory-2 and the Montgomery-Asberg Depression Rating Scale were administered.

No impairment of cognitive performance was found in subjects with BN vs. healthy controls. The higher the cortisol level and “Self-directedness” scores the better the performance on conditional learning, while 17β-estradiol levels showed an opposite pattern of association; “Reward dependence” scores were associated to a worse performance on incidental learning; depressive symptomatology negatively influenced the performance on the WCST.

No cognitive impairment was found in untreated patients with BN in the explored cognitive domains. An influence of neuroendocrine, personality and clinical variables on neurocognitive functioning was found, which might explain discrepancies in literature findings.

An impairment of several cognitive domains has been largely documented in patients with schizophrenia. The present study aimed to investigate the relationships between cognitive functioning, symptomatic remission and functional outcome in schizophrenia.

The performance on the neuropsychological battery “Brief Assessment of Cognition in Schizophrenia (BACS)” has been investigated in clinically remitted (R) and non-remitted (NR) schizophrenic patients. The associations of neuropsychological performance with psychopathological dimensions derived from PANSS and indices of social functioning (as assessed by the Global Assessment of Functioning scale, the Personal and Social Performance scale, the Quality of Life Scale, the UCSD Performance-Based Skills Assessment-Brief Version and the Psychosocial Remission in Schizophrenia scale) were also explored by means of multiple regression (MR) analyses.

Compared with NR, R patients showed a better performance on tests exploring executive functions, processing speed and verbal fluency. Residual negative symptoms and processing speed were independent predictors of functional outcome, while remission status did not enter the MR function.

Our findings suggest that cognitive abilities, in particular processing speed and executive functions, are preserved in patients who are able to reach clinical remission. Independently from the remission state or residual negative symptomatology, processing speed also predicts functional outcome in schizophrenia. Our findings support the view that cognitive dysfunctions in schizophrenia should be targeted by specific treatment intervention, such as neurocognitive rehabilitation.

It has been hypothesized that cognitive remediation with adjunctive psychiatric rehabilitation would be associated with greater improvements in functional outcome than standalone treatment approaches (1).

Moving from these observations our group designed an individualized rehabilitation program including a computerized cognitive training (CCT) and social skills training (SST), which showed promising results (2).

A critical evaluation of recent studies examining standalone and combined treatment approaches included the understanding of the differential impact of the two approaches among crucial areas for future research (3).

The present study compared the effects of CCT and SST on several indices of outcome in psychotic patients. Fifty-eight patients with schizophrenia or schizoaffective disorder were randomly assigned to one of two treatment groups: CCT or SST. Changes in cognitive, psychopathological and psychosocial indices after 6 and 12 months were compared between the two groups.

After both 6 and 12 months, an improvement of psychosocial indices was observed in both groups, while cognitive functions improved only after CCT; the improvement of psychopathological indices, observed in both groups, was greater in the CCT group.

Our findings suggest that CCT is associated with a greater impact than SST on different indices of outcome in psychotic patients. Future research should focus on possible synergistic effects of cognitive remediation and social skills training on functional outcome.