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Abstract Several multivariate prognostic models have been published to predict outcomes in patients with first episode psychosis (FEP), but it remains unclear whether those predictions generalize to independent populations. Using a subset of demographic and clinical baseline predictors, we aimed to develop and externally validate different models predicting functional outcome after a FEP in the context of a schizophrenia-spectrum disorder (FES), based on a previously published cross-validation and machine learning pipeline. A crossover validation approach was adopted in two large, international cohorts (EUFEST, n = 338, and the PSYSCAN FES cohort, n = 226). Scores on the Global Assessment of Functioning scale (GAF) at 12 month follow-up were dichotomized to differentiate between poor (GAF current

Abstract The Positive and Negative Syndrome Scale (PANSS) is the most widely used rating scale to assess psychotic symptoms in patients with schizophrenia and other primary psychoses. However, a definitive consensus regarding its dimensional structure remains elusive. The present work aims to determine the number of dimensions of the scale through a network analysis approach in a sample of individuals experiencing first-episode schizophrenia spectrum disorder (FE-SSD) with minimal or no prior exposure to antipsychotic treatment. Baseline data of 446 participants (age 25.96 ± 5.99 years, 70% males) enrolled in the OPTiMiSE trial were analysed. Exploratory Graph Analysis (EGA) was conducted to evaluate the dimensionality of the PANSS, and a bootstrap approach (bootEGA) was employed to assess model stability. The analysis was replicated, excluding unstable items with stability values below 0.75, until a stable model was achieved. The analysis of the 30 items of the PANSS revealed inadequate structural consistency, resulting in the exclusion of 9 unstable items. The final model comprised 21 symptoms distributed across four communities (Positive, Cognitive/Disorganised, Excited/Aggressive and Negative) but lacked a depressive domain. In conclusion, we propose a concise version of the PANSS, incorporating 21 items, to better assess the core symptoms of the first episode of SSD. This revised version provides clinicians with a robust psychometric tool with reduced administration time, but the complementary administration of a dedicated instrument for evaluating affective symptoms is advisable.

IntroductionIn 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 countries, including Italy. These populations are exposed to several potential stressful experiences which make them vulnerable to psychological distress. In fact, the majority of studies addressing the topic found a higher prevalence of mental disorders, especially post-traumatic stress disorder and major depressive disorder, in refugees and asylum seekers with respect to the general population. However, heterogeneous prevalence rates have been reported among studies, due to methodological factor as well as to the impact of a variety of risk factors related to stressful experiences lived in the country of origin, during the migration journey and in the host country.ObjectivesThe aim of the present study was to assess the prevalence of the main psychiatric diagnoses in a large group of adult refugees and asylum seekers (N=303) in the reception centers of two provinces of the Campania region, as well as to investigate the impact of potential risk factors on the occurrence of psychiatric disorders.MethodsThe diagnosis of psychiatric disorders and the identification of subjects at high risk to develop psychosis were carried out by means of structured diagnostic interviews. The following variables were explored as potential risk/protective factors to the occurrence of psychiatric disorders: socio-demographic variables, migration status (refugees/asylum seekers) and characteristics of the reception center,assessed by means of an ad hoc questionnaire; cognitive indices assessed by using standardized neuropsychological tests; traumatic experiences and level of political terror in the country of origin, assessed by means of reliable and valid self-report questionnaires.ResultsAt least one mental disorder was found in 29.7% of the sample. Most prevalent diagnoses were depressive disorders, anxiety disorders and PTSD. Women showed, with respect to men, a higher prevalence of anxiety disorders, higher trauma levels, and came from more at-risk countries. Higher trauma levels, better cognitive abilities and unemployment and refugee status were associated to the presence of a current psychiatric disorder in the whole sample.ConclusionsOur findings showed a higher prevalence of depressive disorders and PTSD in the sample of refugees and asylum seekers with respect to the general population and highlighted the role of potential risk factors whose identification may guide the implementation of preventive strategies and early treatments in these people.

Academic psychiatry is essential for advancing mental health understanding and treatments. However, women encounter more obstacles hindering their progress in academia than men. This Editorial aims to highlight these obstacles and propose strategies to address them, advocating for a more supportive environment for women psychiatrists’ ongoing growth and development. The importance of supportive environments, fair access to opportunities and structural changes, including initiatives for mentorship, funding and flexible work arrangements, are crucial. Collaboration among governments, institutions and organisations is needed to enhance research infrastructure and promote gender equality. Encouraging and recognising women's contributions in research fosters inclusivity and innovation. Prioritising these efforts is vital for the existence, well-being and success of women in academic psychiatry.

A considerable proportion of patients with schizophrenia perform below population norms on standardized neuropsychological tests, and the performance of those performing within normal range is lower than predicted based on parental education. Cognitive impairment predates the onset of psychosis, is observed during symptom remission and in non-affected first-degree relatives of patients. At the present time, cognitive deficits are regarded as key features of schizophrenia, important determinants of poor psychosocial outcome and targets for both pharmacological and non-pharmacological treatment strategies. A group of eight key opinion leaders reviewed and discussed latest advances in scientific research and current good clinical practices on assessment, management, and treatment of CIAS. In the present paper they summarize the current evidence, identify main gaps between current knowledge and mental health services clinical practice, and provide practical recommendations to reduce the gap.

Despite the functional impact of cognitive deficit in people with psychosis, objective cognitive assessment is not typically part of routine clinical care. This is partly due to the length of traditional assessments and the need for a highly trained administrator. Brief, automated computerised assessments could help to address this issue. We present data from an evaluation of PsyCog, a computerised, non-verbal, mini battery of cognitive tests. Healthy Control (HC) (N = 135), Clinical High Risk (CHR) (N = 233), and First Episode Psychosis (FEP) (N = 301) participants from a multi-centre prospective study were assessed at baseline, 6 months, and 12 months. PsyCog was used to assess cognitive performance at baseline and at up to two follow-up timepoints. Mean total testing time was 35.95 min (SD = 2.87). Relative to HCs, effect sizes of performance impairments were medium to large in FEP patients (composite score G = 1.21, subtest range = 0.52–0.88) and small to medium in CHR patients (composite score G = 0.59, subtest range = 0.18–0.49). Site effects were minimal, and test-retest reliability of the PsyCog composite was good (ICC = 0.82–0.89), though some practice effects and differences in data completion between groups were found. The present implementation of PsyCog shows it to be a useful tool for assessing cognitive function in people with psychosis. Computerised cognitive assessments have the potential to facilitate the evaluation of cognition in psychosis in both research and in clinical care, though caution should still be taken in terms of implementation and study design.

BackgroundThe development of neuroimaging biomarkers in patients with schizophrenia (SCZ) requires a refined clinical characterization. A limitation of the neuroimaging literature is the partial uptake of progress in characterizing disease-related features, particularly negative symptoms (NS) and cognitive impairment (CI). In the present study, we assessed NS and CI using up-to-date instruments and investigated the associations of abnormalities in brain resting-state (rs)-activity with disease-related features.MethodsSixty-two community-dwelling SCZ subjects participated in the study. Multiple regression analyses were performed with the rs-activity of nine regions of interest as dependent variables and disease-related features as explanatory variables.ResultsAttention/vigilance deficits were negatively associated with dorsal anterior cingulate rs-activity and, together with depression, were positively associated with right dorsolateral prefrontal cortex rs-activity. These deficits and impairment of Reasoning/problem-solving, together with conceptual disorganization, were associated with right inferior parietal lobule and temporal parietal junction rs-activity. Independent of other features, the NS Expressive Deficit domain was associated with the left ventral caudate, while the Motivational Deficit was associated with the dorsal caudate rs-activity.ConclusionNeurocognitive deficits and the two negative symptom domains are associated with different neural markers. Replications of these findings could foster the identification of clinically actionable biomarkers of poor functional outcomes.

Abstract There is currently no quantifiable method to predict long-term clinical outcomes in patients presenting with a first episode of psychosis. A major barrier to developing useful markers for this is biological heterogeneity, where many different pathological mechanisms may underly the same set of symptoms in different individuals. Normative modelling has been used to quantify this heterogeneity in established psychotic disorders by identifying regions of the cortex which are thinner than expected based on a normative healthy population range. These brain atypicalities are measured at the individual level and therefore potentially useful in a clinical setting. However, it is still unclear whether alterations in individual brain structure can be detected at the time of the first psychotic episode, and whether they are associated with subsequent clinical outcomes. We applied normative modelling of cortical thickness to a sample of first-episode psychosis patients, with the aim of quantifying heterogeneity and to use any pattern of cortical atypicality to predict symptoms and response to antipsychotic medication at timepoints from baseline up to 95 weeks (median follow-ups = 4). T1-weighted brain magnetic resonance images from the GAP and OPTiMiSE samples were processed with Freesurfer V6.0.0 yielding 148 cortical thickness features. An existing normative model of cortical thickness (n = 37,126) was adapted to integrate data from each clinical site and account for effects of gender and site. Our test sample consisted of control participants (n = 149, mean age = 26, SD = 6.7) and patient data (n = 295, mean age = 26, SD = 6.7), this sample was used for estimating deviations from the normative model and subsequent statistical analysis. For each individual, the 148 cortical thickness features were mapped to centiles of the normative distribution and converted to z-scores reflecting the distance from the population mean. Individual cortical thickness metrics of +/– 2.6 standard deviations from the mean were considered extreme deviations from the norm. We found that no more than 6.4% of psychosis patients had extreme deviations in a single brain region (regional overlap) demonstrating a high degree of heterogeneity. Mann-Whitney U tests were run on z-scores for each region and significantly lower z-scores were observed in FEP patients in the frontal, temporal, parietal and occipital lobes. Finally, linear mixed-effects modelling showed that negative deviations in cortical thickness in parietal and temporal regions at baseline are related to more severe negative symptoms over the medium-term. This study shows that even at the early stage of symptom onset normative modelling provides a framework to identify individualised cortical markers which can be used for early personalised intervention and stratification.

Abstract Background Cognitive impairment (CI) is one of the most prevalent and burdensome consequences of COVID-19 infection, which can persist up to months or even years after remission of the infection. Current guidelines on post-COVID CI are based on available knowledge on treatments used for improving CI in other conditions. The current review aims to provide an updated overview of the existing evidence on the efficacy of treatments for post-COVID CI. Methods A systematic literature search was conducted for studies published up to December 2023 using three databases (PubMed–Scopus–ProQuest). Controlled and noncontrolled trials, cohort studies, case series, and reports testing interventions on subjects with CI following COVID-19 infection were included. Results After screening 7790 articles, 29 studies were included. Multidisciplinary approaches, particularly those combining cognitive remediation interventions, physical exercise, and dietary and sleep support, may improve CI and address the different needs of individuals with post-COVID-19 condition. Cognitive remediation interventions can provide a safe, cost-effective option and may be tailored to deficits in specific cognitive domains. Noninvasive brain stimulation techniques and hyperbaric oxygen therapy showed mixed and preliminary results. Evidence for other interventions, including pharmacological ones, remains sparse. Challenges in interpreting existing evidence include heterogeneity in study designs, assessment tools, and recruitment criteria; lack of long-term follow-up; and under-characterization of samples in relation to confounding factors. Conclusions Further research, grounded on shared definitions of the post-COVID condition and on the accurate assessment of COVID-related CI, in well-defined study samples and with longer follow-ups, is crucial to address this significant unmet need.

Background Stakeholders worldwide increasingly acknowledge the need to address coercive practices in mental healthcare. Options have been described and evaluated in several countries, as noted recently in major policy documents from the World Health Organization (WHO) and World Psychiatric Association (WPA). The WHO's QualityRights initiative promotes human rights and quality of care for persons with mental health conditions and psychosocial disabilities. A position statement from the WPA calls for implementation of alternatives to coercion in mental healthcare. Aims We describe the engagement of both the WHO and WPA in this work. We discuss their mutual aim to support countries in improving human rights and quality of care, as well as the differences between these two organisations in their stated goals related to coercion in mental healthcare: the WHO's approach to eliminate coercion and the WPA's goal to implement alternatives to coercion. Method We outline and critically analyse the common ground between the two organisations, which endorse a similar range of rights-based approaches to promoting non-coercive practices in service provision, including early intervention in prevention and care and other policy and practice changes. Results Advocacy and action based on an agreed need to find practical solutions and advances in this area have the power to build consensus and unify key actors. Conclusions We conclude that persons with lived experience, families, mental health professionals and policy makers are now coming together in several parts of the world to work toward the common goals of improving quality, promoting human rights and addressing coercion in mental health services.

Abstract Background Codes of ethics provide guidance to address ethical challenges encountered in clinical practice. The harmonization of global, regional, and national codes of ethics is important to avoid gaps and discrepancies. Methods We compare the European Psychiatric Association (EPA) and the World Psychiatric Association (WPA) Codes of Ethics, addressing main key points, similarities, and divergences. Results The WPA and EPA codes are inspired by similar fundamental values but do show a few differences. The two codes have a different structure. The WPA code includes 4 sections and lists 5 overarching principles as the basis of psychiatrists’ clinical practice; the EPA code is articulated in 8 sections, lists 4 ethical principles, and several fundamental values. The EPA code does not include a section on psychiatrists’ education and does not contain specific references to domestic violence and death penalty. Differences can be found in how the two codes address the principle of equity: the EPA code explicitly refers to the principle of universal health care, while the WPA code mentions the principle of equity as reflected in the promotion of distributive justice. Conclusions We recommend that both WPA and EPA periodically update their ethical codes to minimize differences, eliminate gaps, and help member societies to develop or revise national codes in line with the principles of the associations they belong to. Minimizing differences between national and international codes and fostering a continuous dialogue on ethical issues will provide guidance for psychiatrists and will raise awareness of the importance of ethics in our profession.

IntroductionIn this study we assessed the contribution of psychopathology, including the two domains of negative symptoms (motivational deficit and expressive deficit), processing speed as an index of neurocognition, and emotion recognition, as an index of social cognition, to poor functional outcomes in people with schizophrenia.MethodsThe Positive and Negative Syndrome Scale was used to evaluate positive symptoms and disorganization and the Brief Negative Symptom Scale to assess negative symptoms. The Symbol Coding and the Trail Making Test A and B were used to rate processing speed and the Facial Emotion Identification Test to assess emotion recognition. Functional outcome was assessed with the Personal and Social Performance Scale (PSP). Regression analyses were performed to identify predictors of functional outcome. Mediation analyses was used to investigate whether social cognition and negative symptom domains fully or partially mediated the impact of processing speed on functional outcome.ResultsOne hundred and fifty subjects from 8 different European centers were recruited. Our data showed that the expressive deficit predicted global functioning and together with motivational deficit fully mediated the effects of neurocognition on it. Motivational deficit was a predictor of personal and social functioning and fully mediated neurocognitive impairment effects on the same outcome. Both motivational deficit and neurocognitive impairment predicted socially useful activities, and the emotion recognition domain of social cognition partially mediated the impact of neurocognitive deficits on this outcome.ConclusionsOur results indicate that pathways to functional outcomes are specific for different domains of real-life functioning and that negative symptoms and social cognition mediate the impact of neurocognitive deficits on different domains of functioning. Our results suggest that both negative symptoms and social cognition should be targeted by psychosocial interventions to enhance the functional impact of neurocognitive remediation.

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.

Abstract Definition of an appropriate and personalized treatment plan focused on long-term outcomes is crucial in the management of schizophrenia. Following review of the literature, a panel of six leading psychiatrists discussed the importance of clear and shared long-term goals when initiating antipsychotic treatment in light of their clinical experience. The importance of establishing shared and progressive treatment objectives was stressed, which should be tailored based on the patient’s characteristics, goals, and preferences. Consensus emerged on the key role that therapeutic alliance and patient empowerment play throughout the course of treatment. Reduction in symptoms in the acute phase along with good efficacy and tolerability in the maintenance phase emerged as essential features of a therapy that can favor achievement of long-term outcomes. Long-acting injectable (LAI) antipsychotics enhance adherence to treatment compared to oral formulations and have been shown to be effective in the maintenance phase. Currently available LAIs are characterized by a delayed onset of action and require a loading dose or oral supplementation to achieve therapeutic concentrations. Risperidone ISM® is a novel LAI antipsychotic with fast and sustained release of antipsychotic, reaching therapeutic plasma levels within a few hours after administration without oral supplementation or loading doses. Risperidone ISM® has been shown to rapidly control symptoms in patients with an acute exacerbation of schizophrenia and to be effective and well tolerated as maintenance treatment irrespective of the severity of initial symptoms. It thus represents a valuable and novel therapeutic option in management of schizophrenia.

Background The structure of negative symptoms of schizophrenia is still a matter of controversy. Although a two-dimensional model (comprising the expressive deficit dimension and the motivation and pleasure dimension) has gained a large consensus, it has been questioned by recent investigations. Aims To investigate the latent structure of negative symptoms and its stability over time in people with schizophrenia using network analysis. Method Negative symptoms were assessed in 612 people with schizophrenia using the Brief Negative Symptom Scale (BNSS) at baseline and at 4-year follow-up. A network invariance analysis was conducted to investigate changes in the network structure and strength of connections between the two time points. Results The network analysis carried out at baseline and follow-up, supported by community detection analysis, indicated that the BNSS's items aggregate to form four or five distinct domains (avolition/asociality, anhedonia, blunted affect and alogia). The network invariance test indicated that the network structure remained unchanged over time (network invariance test score 0.13; P = 0.169), although its overall strength decreased (6.28 at baseline, 5.79 at follow-up; global strength invariance test score 0.48; P = 0.016). Conclusions The results lend support to a four- or five-factor model of negative symptoms and indicate overall stability over time. These data have implications for the study of pathophysiological mechanisms and the development of targeted treatments for negative symptoms.

Abstract Background The European Psychiatric Association (EPA) is an organization that speaks on behalf of its individual members and members of National Psychiatric Associations (NPAs). The aim of this study to identify and investigate current contents of ethical codes and practices in the countries belonging to EPA. Methods The study is an expert survey sent out to 44 representatives of 30 NPAs covering the following topics: the existence of national bodies dealing with ethical issues in psychiatry, the availability of documents relevant to ethical issues, the types of ethical issues addressed at the national level, and the current and envisaged ethical debates. Results Out of 44 experts invited to participate in the study, 31 NPAs from 30 countries responded (response rate 70.45%). In the majority of countries, the general mission statement serves as the main document covering ethical issues in psychiatry. Most frequently, internal documents were reported to address medical malpractice, workplace bullying, plagiarism, academic fraud, sexual abuse, and discrimination/racism. Furthermore, internal documents cover the ethical assessment of potentially controversial procedures, including psychosurgery, euthanasia, and pregnancy termination. The most important topics for debate at the level of NPAs/EPA were associated with violations of clinical practice standards and human rights. Conclusions NPAs are active in the field of professional ethics, defining ethical standards related to interactions among professionals and services provided by mental health care professionals. Future collaboration of NPAs, under the umbrella of the EPA, could allow to develop a database of local ethical documents that would be translated into English and accessible to all EPA members.

Abstract Background Despite efforts toward greater gender equality in clinical and academic psychiatry in recent years, more information is needed about the challenges in professional development within psychiatry, and how these may vary with gender. Methods A cross-sectional 27-item online survey was conducted with psychiatrists and psychiatric trainee members of the European Psychiatric Association. Results A total of 561 psychiatrists and psychiatric trainees from 35 European countries participated representing a response rate of 52.8% for women and 17.7% for men from a total sample of 1,580. The specific challenges that women face in their professional development fall into two categories. One comprised women’s negative attitudes concerning their abilities in self-promotion and networking. The other identified environmental barriers related to lack of opportunity and support and gender discrimination. Compared to men, women reported higher rates of gender discrimination in terms of professional advancement. Women were less likely to agree that their institutions had regular activities promoting inclusion, diversity, and training to address implicit gender bias. Working in high-income countries compared to middle-income countries relates to reporting institutional support for career progression. Conclusions These findings are an open call to hospital leaders, deans of medical schools, and department chairs to increase efforts to eradicate bias against women and create safer, inclusive, and respectful environments for all psychiatrists, a special call to women psychiatrists to be aware of inner tendencies to avoid self-promotion and networking and to think positively and confidently about themselves and their abilities.

Abstract Background Different electrophysiological (EEG) indices have been investigated as possible biomarkers of schizophrenia. However, these indices have a very limited use in clinical practice, as their associations with clinical and functional outcomes remain unclear. This study aimed to investigate the associations of multiple EEG markers with clinical variables and functional outcomes in subjects with schizophrenia (SCZs). Methods Resting-state EEGs (frequency bands and microstates) and auditory event-related potentials (MMN-P3a and N100-P3b) were recorded in 113 SCZs and 57 healthy controls (HCs) at baseline. Illness- and functioning-related variables were assessed both at baseline and at 4-year follow-up in 61 SCZs. We generated a machine-learning classifier for each EEG parameter (frequency bands, microstates, N100-P300 task, and MMN-P3a task) to identify potential markers discriminating SCZs from HCs, and a global classifier. Associations of the classifiers’ decision scores with illness- and functioning-related variables at baseline and follow-up were then investigated. Results The global classifier discriminated SCZs from HCs with an accuracy of 75.4% and its decision scores significantly correlated with negative symptoms, depression, neurocognition, and real-life functioning at 4-year follow-up. Conclusions These results suggest that a combination of multiple EEG alterations is associated with poor functional outcomes and its clinical and cognitive determinants in SCZs. These findings need replication, possibly looking at different illness stages in order to implement EEG as a possible tool for the prediction of poor functional outcome.

Abstract Background Deficits in social cognition (SC) are significantly related to community functioning in schizophrenia (SZ). Few studies investigated longitudinal changes in SC and its impact on recovery. In the present study, we aimed: (a) to estimate the magnitude and clinical significance of SC change in outpatients with stable SZ who were assessed at baseline and after 4 years, (b) to identify predictors of reliable and clinically significant change (RCSC), and (c) to determine whether changes in SC over 4 years predicted patient recovery at follow-up. Methods The reliable change index was used to estimate the proportion of true change in SC, not attributable to measurement error. Stepwise multiple logistic regression models were used to identify the predictors of RCSC in a SC domain (The Awareness of Social Inference Test [TASIT]) and the effect of change in TASIT on recovery at follow-up. Results In 548 participants, statistically significant improvements were found for the simple and paradoxical sarcasm of TASIT scale, and for the total score of section 2. The reliable change index was 9.8. A cut-off of 45 identified patients showing clinically significant change. Reliable change was achieved by 12.6% and RCSC by 8% of participants. Lower baseline TASIT sect. 2 score predicted reliable improvement on TASIT sect. 2. Improvement in TASIT sect. 2 scores predicted functional recovery, with a 10-point change predicting 40% increase in the probability of recovery. Conclusions The RCSC index provides a conservative way to assess the improvement in the ability to grasp sarcasm in SZ, and is associated with recovery.

To date, the role of family members in caring for relatives affected by schizophrenia has focused largely on the negative aspects of impact of the illness. The present study aimed to: (1) assess family functioning and burden of care in caregivers living in Northern, Central, and Southern Italy who looked after subjects affected by chronic schizophrenia; (2) evaluate the relationship between aspects of family functioning and burden of care, in particular personal growth (PG) of caregivers; and (3) identify variables capable of affecting PG of caregivers. A total of 136 caregivers (mean length of illness of family member more than 20 years) were recruited from 9 Italian research sites and evaluated in terms of “positive” family functioning–problem-solving, communication skills and personal goals Family Functioning Questionnaire (FFQ), burden of care, and PG Family Problems Questionnaire (FPQ). Caregivers reported an overall good family functioning with a relatively low objective and subjective burden of care. The latter was positively correlated with length of illness, with women showing a higher subjective burden than men. Reduced problem-solving skills and ability of each family member to pursue personal goals were both associated with reduced objective and subjective burden which, conversely, were both increased by inadequate support and scarce positive comments from relatives and friends. Approximately 50% of caregivers stated that “they had learned something positive from the situation,” highlighting a statistically higher proportion of caregivers in southern Italy than in northern and central Italy. Caregivers’ PG was associated with good family functioning, adequate professional support, and positive comments. PG also seemed to be positively influenced by support from relatives and friends (O.R. 14.306). The numerous challenges and positive aspects associated with caregiving should be duly acknowledged by mental health services and integrated into routine clinical assessment and intervention framework.

The integration of pharmacotherapy with psychosocial interventions has an important role to play in the improvement of functional outcome of subjects with schizophrenia (SCZ), in all stages of the disorder. It is essential for the adequate management of unmet therapeutic needs, such as negative symptoms and cognitive dysfunctions which account for most of the functional impairment of subjects with SCZ and do not respond to available antipsychotics. Enhancing the knowledge on factors involved in the effectiveness of integrated treatment plans is an important step forward for SCZ care. This review aims to identify factors that might influence the impact of integrated treatments on functional outcome. Most studies on the impact of psychosocial treatments on functional outcome of subjects with SCZ did not control for the effect of prescribed antipsychotics or concomitant medications. However, several factors relevant to ongoing pharmacological treatment might influence the outcome of integrated therapy, with an impact on the adherence to treatment (e.g., therapeutic alliance and polypharmacotherapy) or on illness-related factors addressed by the psychosocial interventions (e.g., cognitive dysfunctions or motivational deficits). Indirect evidence suggests that treatment integration should consider the possible detrimental effects of different antipsychotics or concomitant medications on cognitive functions, as well as on secondary negative symptoms. Cognitive dysfunctions can interfere with participation to an integrated treatment plan and can be worsened by extrapyramidal or metabolic side effects of antipsychotics, or concomitant treatment with anticholinergics or benzodiazepines. Secondary negative symptoms, due to positive symptoms, sedation, extrapyramidal side effects or untreated depression, might cause early drop-out and poor adherence to treatment. Researchers and clinicians should examine all the above-mentioned factors and implement appropriate and personalized integrated treatments to improve the outcome of SCZ.

Abstract A consensus has not yet been reached regarding the accuracy of people with schizophrenia in self-reporting their real-life functioning. In a large (n = 618) cohort of stable, community-dwelling schizophrenia patients we sought to: (1) examine the concordance of patients’ reports of their real-life functioning with the reports of their key caregiver; (2) identify which patient characteristics are associated to the differences between patients and informants. Patient-caregiver concordance of the ratings in three Specific Level of Functioning Scale (SLOF) domains (interpersonal relationships, everyday life skills, work skills) was evaluated with matched-pair t tests, the Lin’s concordance correlation, Somers’ D, and Bland–Altman plots with limits of agreement (LOA). Predictors of the patient-caregiver differences in SLOF ratings were assessed with a linear regression with multivariable fractional polynomials. Patients’ self-evaluation of functioning was higher than caregivers’ in all the evaluated domains of the SLOF and 17.6% of the patients exceeded the LOA, thus providing a self-evaluation discordant from their key caregivers. The strongest predictors of patient-caregiver discrepancies were caregivers’ ratings in each SLOF domain. In clinically stable outpatients with a moderate degree of functional impairment, self-evaluation with the SLOF scale can become a useful, informative and reliable clinical tool to design a tailored rehabilitation program.

Subjects affected by schizophrenia present significant deficits in various aspects of social cognition, such as emotion processing, social perception and theory of mind (ToM). These deficits have a greater impact than symptoms on occupational and social functioning. Therefore, social cognition represents an important therapeutic target in people with schizophrenia. Recent meta-analyses showed that social cognition training (SCT) is effective in improving social cognition in subjects with schizophrenia; however, real-life functioning is not always ameliorated. Integration of SCT with an intervention targeting metacognitive abilities might improve the integration of social cognitive skills to daily life functioning. Our research group has implemented a new individualized rehabilitation program: the Social Cognition Individualized Activities Lab, SoCIAL, which integrates SCT with a module for narrative enhancement, an intervention targeting metacognitive abilities. The present multi-center randomized controlled study will compare the efficacy of SoCIAL and treatment as usual (TAU) in subjects diagnosed with a schizophrenia-spectrum disorder. The primary outcome will be the improvement of social cognition and real-life functioning; while the secondary outcome will be the improvement of symptoms, functional capacity and neurocognition. The results of this study will add empirical evidence to the benefits and feasibility of SCT and narrative enhancement in people with schizophrenia-spectrum disorders.

BackgroundThe clinical high-risk for psychosis (CHR-P) paradigm was introduced to detect individuals at risk of developing psychosis and to establish preventive strategies. While current prediction of outcomes in the CHR-P state is based mostly on the clinical assessment of presenting features, several emerging biomarkers have been investigated in an attempt to stratify CHR-P individuals according to their individual trajectories and refine the diagnostic process. However, heterogeneity across subgroups is a key challenge that has limited the impact of the CHR-P prediction strategies, as the clinical validity of the current research is limited by a lack of external validation across sites and modalities. Despite these challenges, electroencephalography (EEG) biomarkers have been studied in this field and evidence suggests that EEG used in combination with clinical assessments may be a key measure for improving diagnostic and prognostic accuracy in the CHR-P state. The PSYSCAN EEG study is an international, multi-site, multimodal longitudinal project that aims to advance knowledge in this field.MethodsParticipants at 6 international sites take part in an EEG protocol including EEG recording, cognitive and clinical assessments. CHR-P participants will be followed up after 2 years and subcategorised depending on their illness progression regarding transition to psychosis. Differences will be sought between CHR-P individuals and healthy controls and between CHR-P individuals who transition and those who do not transition to psychosis using data driven computational analyses.DiscussionThis protocol addresses the challenges faced by previous studies of this kind to enable valid identification of predictive EEG biomarkers which will be combined with other biomarkers across sites to develop a prognostic tool in CHR-P. The PSYSCAN EEG study aims to pave the way for incorporating EEG biomarkers in the assessment of CHR-P individuals, to refine the diagnostic process and help to stratify CHR-P subjects according to risk of transition. This may improve our understanding of the CHR-P state and therefore aid the development of more personalized treatment strategies.

Abstract Background 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. 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 analyzed. The sample included 446 participants (age 40.0 ± 10.9 years, 70% males). The network was estimated with a Gaussian graphical model, using scores on individual items of the positive and negative syndrome scale (PANSS), the Calgary depression scale for schizophrenia, and the personal and social performance 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. The most central nodes (EI) were Delusions, Emotional Withdrawal, Depression, and Depressed Mood. Bridge nodes included Depression, Conceptual Disorganization, 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. 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.

Abstract Background Impairment in a wide range of cognitive abilities has been consistently reported in individuals with schizophrenia. Both neurocognitive and social cognitive deficits are thought to underlie severe functional disabilities associated with schizophrenia. Despite the key role in schizophrenia outcome, cognition is still poorly assessed in both research and clinical settings. Methods In this guidance paper, we provide a systematic review of the scientific literature and elaborate several recommendations for the assessment of cognitive functions in schizophrenia both in research settings and in real-world clinical practice. Results Expert consensus and systematic reviews provided guidance for the optimal assessment of cognitive functions in schizophrenia. Based on the reviewed evidence, we recommend a comprehensive and systematic assessment of neurocognitive and social cognitive domains in schizophrenia, in all phases of the disorder, as well as in subjects at risk to develop psychosis. This European Psychiatric Association guidance recommends not only the use of observer reports but also self-reports and interview-based cognitive assessment tools. The guidance also provides a systematic review of the state of the art of assessment in the first episode of psychosis patients and in individuals at risk for psychosis. Conclusion The comprehensive review of the evidence and the recommendations might contribute to advance the field, allowing a better cognitive assessment, and avoiding overlaps with other psychopathological dimensions. The dissemination of this guidance paper may promote the development of shared guidelines concerning the assessment of cognitive functions in schizophrenia, with the purpose to improve the quality of care and to obtain recovery.

Abstract Background Although cognitive impairment is a core symptom of schizophrenia related to poorer outcomes in different functional domains, it still remains a major therapeutic challenge. To date, no comprehensive treatment guidelines for cognitive impairment in schizophrenia are implemented. Methods The aim of the present guidance paper is to provide a comprehensive meta-review of the current available evidence-based treatments for cognitive impairment in schizophrenia. The guidance is structured into three sections: pharmacological treatment, psychosocial interventions, and somatic treatments. Results Based on the reviewed evidence, this European Psychiatric Association guidance recommends an appropriate pharmacological management as a fundamental starting point in the treatment of cognitive impairment in schizophrenia. In particular, second-generation antipsychotics are recommended for their favorable cognitive profile compared to first-generation antipsychotics, although no clear superiority of a single second-generation antipsychotic has currently been found. Anticholinergic and benzodiazepine burdens should be kept to a minimum, considering the negative impact on cognitive functioning. Among psychosocial interventions, cognitive remediation and physical exercise are recommended for the treatment of cognitive impairment in schizophrenia. Noninvasive brain stimulation techniques could be taken into account as add-on therapy. Conclusions Overall, there is definitive progress in the field, but further research is needed to develop specific treatments for cognitive impairment in schizophrenia. The dissemination of this guidance paper may promote the development of shared guidelines concerning the treatment of cognitive functions in schizophrenia, with the purpose to improve the quality of care and to achieve recovery in this population.

BackgroundNegative symptoms are usually evaluated with scales based on observer ratings and up to now self-assessments have been overlooked. The aim of this paper was to validate the Self-evaluation of Negative Symptoms (SNS) in a large European sample coming from 12 countries. We wanted to demonstrate: (1) good convergent and divergent validities; (2) relationships between SNS scores and patients' functional outcome; (3) the capacity of the SNS compared to the Brief Negative Symptom Scale (BNSS) to detect negative symptoms; and (4) a five-domain construct in relation to the 5 consensus domains (social withdrawal, anhedonia, alogia, avolition, blunted affect) as the best latent structure of SNS.MethodsTwo hundred forty-five subjects with a DSM-IV diagnosis of schizophrenia completed the SNS, the Positive and Negative Syndrome Scale (PANSS), the BNSS, the Calgary Depression Scale for Schizophrenia (CDSS), and the Personal and Social Performance (PSP) scale. Spearman's Rho correlations, confirmatory factor analysis investigating 4 models of the latent structure of SNS and stepwise multiple regression were performed.ResultsSignificant positive correlations were observed between the total score of the SNS and the total scores of the PANSS negative subscale (r = 0.37; P < 0.0001) and the BNSS (r = 0.43; p < 0.0001). SNS scores did not correlate with the level of insight, parkinsonism, or the total score of the PANSS positive subscale. A positive correlation was found between SNS and CDSS (r = 0.35; p < 0.0001). Among the 5 SNS subscores, only avolition subscores entered the regression equation explaining a lower functional outcome. The 1-factor and 2-factor models provided poor fit, while the 5-factor model and the hierarchical model provided the best fit, with a small advantage of the 5-factor model. The frequency of each negative dimension was systematically higher using the BNSS and the SNS vs. the PANSS and was higher for alogia and avolition using SNS vs. BNSS.ConclusionIn a large European multicentric sample, this study demonstrated that the SNS has: (1) good psychometric properties with good convergent and divergent validities; (2) a five-factor latent structure; (3) an association with patients' functional outcome; and (4) the capacity to identify subjects with negative symptoms that is close to the BNSS and superior to the PANSS negative subscale.

The aim of the present study was to examine the neurobiological correlates of the two negative symptom domains of schizophrenia, the Motivational Deficit domain (including avolition, anhedonia, and asociality) and the Expressive Deficit domain (including blunted affect and alogia), focusing on brain areas that are most commonly found to be associated with negative symptoms in previous literature. Resting-state (rs) fMRI data were analyzed in 62 subjects affected by schizophrenia (SZs) and 46 healthy controls (HCs). The SZs, compared to the HCs, showed higher rs brain activity in the right inferior parietal lobule and the right temporoparietal junction, and lower rs brain activity in the right dorsolateral prefrontal cortex, the bilateral anterior dorsal cingulate cortex, and the ventral and dorsal caudate. Furthermore, in the SZs, the rs brain activity in the left orbitofrontal cortex correlated with negative symptoms (r = −0.436, p = 0.006), in particular with the Motivational Deficit domain (r = −0.424, p = 0.002), even after controlling for confounding factors. The left ventral caudate correlated with negative symptoms (r = −0.407, p = 0.003), especially with the Expressive Deficit domain (r = −0.401, p = 0.003); however, these results seemed to be affected by confounding factors. In line with the literature, our results demonstrated that the two negative symptom domains might be underpinned by different neurobiological mechanisms.

The identification of factors associated with functional outcome of subjects with schizophrenia is a great challenge in current research oriented to the personalization of care. The Italian Network for Research on Psychoses (NIRP) is a network of 26 university psychiatric clinics and/or mental health departments aimed to carry out multicenter research projects to improve the standards of prevention, diagnosis, and treatments of schizophrenia. The network has promoted 2 main studies, a cross-sectional one and a longitudinal one and seven “add-on” studies. The cross-sectional study of the network included 921 subjects with schizophrenia, 379 unaffected first-degree relatives of these patients, and 780 healthy controls. Results from this study documented that social and non-social cognition, functional capacity, negative symptoms, resilience, and family or social incentives strongly influence a measure of global functioning. The follow-up study included 618 patients from the original sample and has produced evidence of the key role of cognition, functional capacity, the experiential domain of negative symptoms, and everyday life skills in predicting functional outcome. The longitudinal study demonstrated that social cognition and the experiential domain of negative symptoms had an impact on interpersonal functioning, while non-social cognition had an impact on everyday life skills. Both non-social cognition and social cognition predicted work skills. The research question concerning the relationships of cognitive impairment and negative symptoms has been investigated with an innovative approach, using a structural equation model (SEM) and a network analysis. Both analyses demonstrated that only the experiential domain of negative symptoms had a distinct direct effect on functioning. The network analysis showed that expressive deficit was connected to functional capacity, as were social and non-social cognitive variables, and to disorganization. These findings were confirmed by the follow-up study. The add-on studies showed distinct electrophysiological correlates of the two negative symptom domains and the partial overlap between disorganization and neurocognitive impairment. Moreover, they identified and characterized a specific subgroup of patients suffering from schizophrenia with autism spectrum symptoms. The NIRP studies have implications for personalized management of patients with schizophrenia and highlight the need for a careful assessment of several domains rarely evaluated in clinical settings.

Background: Negative symptoms represent a heterogeneous dimension with a strong impact on functioning of subjects with schizophrenia (SCZ). Five constructs are included in this dimension: anhedonia, asociality, avolition, blunted affect, and alogia. Factor analyses revealed that these symptoms cluster in two domains: experiential domain (avolition, asociality, and anhedonia) and the expressive deficit (alogia and blunted affect), that might be linked to different neurobiological alterations. Few studies investigated associations between N100, an electrophysiological index of early sensory processing, and negative symptoms, reporting controversial results. However, none of these studies investigated electrophysiological correlates of the two negative symptom domains.Objectives: The aim of our study was to evaluate, within the multicenter study of the Italian Network for Research on Psychoses, the relationships between N100 and negative symptom domains in SCZ.Methods: Auditory N100 was analyzed in 114 chronic stabilized SCZ and 63 healthy controls (HCs). Negative symptoms were assessed with the Brief Negative Symptom Scale (BNSS). Repeated measures ANOVA and correlation analyses were performed to evaluate differences between SCZ and HCs and association of N100 features with negative symptoms.Results: Our findings demonstrated a significant N100 amplitude reduction in SCZ compared with HCs. In SCZ, N100 amplitude for standard stimuli was associated with negative symptoms, in particular with the expressive deficit domain. Within the expressive deficit, blunted affect and alogia had the same pattern of correlation with N100.Conclusion: Our findings revealed an association between expressive deficit and N100, suggesting that these negative symptoms might be related to deficits in early auditory processing in SCZ.

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. In the present review, we summarize the literature on gender differences in schizophrenia relevant to clinical and social outcome as well as their determinants, focusing on clinical variables, while gender differences on biological factors which may have an impact on the outcome of the disorder were not included herewith. Consistent findings include, in male with respect to female patients, an earlier age of illness onset limited to early- and middle-onset schizophrenia, a worse premorbid functioning, a greater severity of negative symptoms, a lower severity of affective symptoms and a higher rate of comorbid alcohol/substance abuse. Discrepant findings have been reported on gender differences in positive symptoms and in social and non-social cognition, as well as in functional outcome and rates of recovery. In fact, despite the overall finding of a more severe clinical picture in males, this does not seem to translate into a worse outcome. From the recent literature emerges that, although some findings on gender differences in schizophrenia are consistent, there are still aspects of clinical and functional outcome which need clarification by means of further studies taking into account several methodological issues.

Cognitive dysfunctions represent a core feature of schizophrenia-spectrum disorders due to their presence throughout different illness stages and their impact on functioning. Abnormalities in electrophysiology (EEG) measures are highly related to these impairments, but the use of EEG indices in clinical practice is still limited. A systematic review of articles using Pubmed, Scopus and PsychINFO was undertaken in November 2021 to provide an overview of the relationships between EEG indices and cognitive impairment in schizophrenia-spectrum disorders. Out of 2433 screened records, 135 studies were included in a qualitative review. Although the results were heterogeneous, some significant correlations were identified. In particular, abnormalities in alpha, theta and gamma activity, as well as in MMN and P300, were associated with impairments in cognitive domains such as attention, working memory, visual and verbal learning and executive functioning during at-risk mental states, early and chronic stages of schizophrenia-spectrum disorders. The review suggests that machine learning approaches together with a careful selection of validated EEG and cognitive indices and characterization of clinical phenotypes might contribute to increase the use of EEG-based measures in clinical settings.

Abstract Background The European impact of the clinical high risk for psychosis (CHR-P) paradigm is constrained by the lack of critical mass (detection) to power prognostic and preventive interventions. Methods An ITAlian partnership for psychosis prevention (ITAPP) was created across CHR-P centers, which were surveyed to describe: (a) service, catchment area, and outreach; (b) service users; and (c) interventions and outcomes. Descriptive statistics and Kaplan–Meier failure function complemented the analyses. Results The ITAPP included five CHR-P clinical academic centers established from 2007 to 2018, serving about 13 million inhabitants, with a recruitment capacity of 277 CHR-P individuals (mean age: 18.7 years, SD: 4.8, range: 12–39 years; 53.1% females; 85.7% meeting attenuated psychotic symptoms; 85.8% without any substance abuse). All centers were multidisciplinary and included adolescents and young adults (transitional) primarily recruited through healthcare services. The comprehensive assessment of at-risk mental state was the most widely used instrument, while the duration of follow-up, type of outreach, and preventive interventions were heterogeneous. Across 205 CHR-P individuals with follow up (663.7 days ± 551.7), the cumulative risk of psychosis increased from 8.7% (95% CI 5.3–14.1) at 1 year to 15.9% (95% CI 10.6–23.3) at 2 years, 21.8% (95% CI 14.9–31.3) at 3 years, 34.8% (95% CI 24.5–47.9) at 4 years, and 51.9% (95% CI 36.3–69.6) at 5 years. Conclusions The ITAPP is one of the few CHR-P clinical research partnerships in Europe for fostering detection, prognosis, and preventive care, as well as for translating research innovations into practice.

AbstractBackgroundPatients with schizophrenia spectrum disorders (SSD) have worse physical health and reduced life expectancy compared to the general population. In 2009, the European Psychiatric Association, the European Society of Cardiology and the European Association for the Study of Diabetes published a position paper aimed to improve cardiovascular and diabetes care in patients with severe mental illnesses. However, the initiative did not produce the expected results. Experts in SSD or in cardiovascular and metabolic diseases convened to identify main issues relevant to management of cardiometabolic risk factors in schizophrenia patients and to seek consensus through the Delphi method.MethodsThe steering committee identified four topics: 1) cardiometabolic risk factors in schizophrenia patients; 2) cardiometabolic risk factors related to antipsychotic treatment; 3) differences in antipsychotic cardiometabolic profiles; 4) management of cardiometabolic risk. Twelve key statements were included in a Delphi questionnaire delivered to a panel of expert European psychiatrists.ResultsConsensus was reached for all statements with positive agreement higher than 85% in the first round. European psychiatrists agreed on: 1) high cardiometabolic risk in patients with SSD, 2) importance of correct risk management of cardiometabolic diseases, from lifestyle modification to treatment of risk factors, including the choice of antipsychotic drugs with a favourable cardiometabolic profile. The expert panel identified the psychiatrist as the central coordinating figure of management, possibly assisted by other specialists and general practitioners.ConclusionsThis study demonstrates high level of agreement among European psychiatrists regarding the importance of cardiovascular risk assessment and management in subjects with SSD.

Abstract Background Mental disorders in comorbidity with chronic skin diseases may worsen disease outcome and patients’ quality of life. We hypothesized the comorbidity of depression, anxiety syndromes, or symptoms as attributable to biological mechanisms that the combined diseases share. Methods We conducted a systematic review based on the Preferred Reporting Items for Systematic Review and Meta-Analysis statement searching into PubMed, PsycInfo, and Scopus databases. We examined the literature regarding the comorbidity of psoriasis (Ps), atopic dermatitis (AD), or hidradenitis suppurativa with depression and/or anxiety in adults ≥18 years and the hypothetical shared underlying biological mechanisms. Results Sixteen studies were analyzed, mostly regarding Ps and AD. Brain-derived neurotrophic factor/tropomyosin receptor kinase B signaling and nuclear factor kappa-light-chain-enhancer of activated B cells/p38 mitogen-activated protein kinase pathways arose as shared mechanisms in Ps animal models with depression- and/or anxiety-like behaviors. Activated microglia and neuroinflammatory responses emerged in AD depressive models. As to genetic studies, atopic-dermatitis patients with comorbid anxiety traits carried the short variant of serotonin transporter and a polymorphism of the human translocator protein gene. A GA genotype of catechol-O-methyltransferase gene was instead associated with Ps. Reduced natural killer cell activity, IL-4, serotonin serum levels, and increased plasma cortisol and IgE levels were hypothesized in comorbid depressive AD patients. In Ps patients with comorbid depression, high serum concentrations of IL-6 and IL-18, as well as IL-17A, were presumed to act as shared inflammatory mechanisms. Conclusions Further studies should investigate mental disorders and chronic skin diseases concurrently across patients’ life course and identify their temporal relation and biological correlates. Future research should also identify biological characteristics of individuals at high risk of the comorbid disorders and associated complications.

Social dysfunctions (SD) are frequently observed in subjects with schizophrenia. Some of these dysfunctions are also observed in other neuropsychiatric disorders such as autism spectrum disorders (ASD), major depression, bipolar disorder, or Alzheimer disease. Recently, a characterization of a specific type of SD in schizophrenia has been proposed, with the concept of dis-sociality, which form the core aspect of “Schizophrenic Autism” (SA). The present study aimed to explore the presence in people with schizophrenia of SA, independent of other autistic traits, which can be often found in schizophrenia and other neurodevelopmental disorders. We used a structured interview—the Autism Rating Scale (ARS), an instrument devised to detect and measure SA. Fifty-one outpatients affected by schizophrenia (26 remitted, SCZ-r) and 28 affected by bipolar disorder type 1, with psychotic features, in the euthymic phase (BD-e) were recruited. Before assessing the specificity for schizophrenia of SA, we tested the internal consistency, the convergent and divergent validity of the ARS in the schizophrenia sample. Specificity was assessed by examining potential differences in ARS scores between SCZ-r and BD-e subjects. ARS showed good internal consistency, as well as convergent and divergent validity. ARS items were more frequently of moderate severity in SCZ-r than in BD-e subjects. This scale can contribute to establish more precise phenomenal boundaries between schizophrenia and bipolar disorder, and opens up the possibility of identifying a different type of SD in schizophrenia, independent of autistic traits and negative symptoms, which might benefit from different treatments.

Negative symptoms (NS) represent a heterogeneous dimension of schizophrenia (SCZ), associated with a poor functional outcome. A dysregulated dopamine (DA) system, including a reduced D1 receptor activation in the prefrontal cortex, DA hypoactivity in the caudate and alterations in D3 receptor activity, seems to contribute to the pathogenesis of NS. However, failure to take into account the NS heterogeneity has slowed down progress in research on their neurobiological correlates and discoveries of new effective treatments. A better neurobiological characterization of NS is needed, and this requires objective quantification of their features that can be applied in translational models, such as animal models and human inducible pluripotent stem cells (iPSC). In this review we summarize the evidence for dopaminergic alterations relevant to NS in translational animal models focusing on dysfunctional motivation, a core aspect of NS. Among others, experiments on mutant rodents with an overexpression of DA D2 or D3 receptors and the dopamine deficient mice are discussed. In the second part we summarize the findings from recent studies using iPSC to model the pathogenesis of SCZ. By retaining the genetic background of risk genetic variants, iPSC offer the possibility to study the effect of de novo mutations or inherited polymorphisms from subgroups of patients and their response to drugs, adding an important tool for personalized psychiatry. Given the key role of DA in NS, we focus on findings of iPSC-derived DA neurons. Since implementation of iPSC-derived neurons to study the neurobiology of SCZ is a relatively recent acquisition, the available data are limited. We highlight some methodological aspects of relevance in the interpretation of in vitro testing results, including limitations and strengths, offering a critical viewpoint for the implementation of future pharmacological studies aimed to the discovery and characterization of novel treatments for NS.

Abstract Background Autism spectrum disorders (ASDs) and schizophrenia spectrum disorders (SSDs), although conceptualized as separate entities, may share some clinical and neurobiological features. ASD symptoms may have a relevant role in determining a more severe clinical presentation of schizophrenic disorder but their relationships with cognitive aspects and functional outcomes of the disease remain to be addressed in large samples of individuals. Aims To investigate the clinical, cognitive, and functional correlates of ASD symptoms in a large sample of people diagnosed with schizophrenia. Methods The severity of ASD symptoms was measured with the PANSS Autism Severity Scale (PAUSS) in 921 individuals recruited for the Italian Network for Research on Psychoses multicenter study. Based on the PAUSS scores, three groups of subjects were compared on a wide array of cognitive and functional measures. Results Subjects with more severe ASD symptoms showed a poorer performance in the processing speed (p = 0.010), attention (p = 0.011), verbal memory (p = 0.035), and social cognition (p = 0.001) domains, and an overall lower global cognitive composite score (p = 0.010). Subjects with more severe ASD symptoms also showed poorer functional capacity (p = 0.004), real-world interpersonal relationships (p

• Better insight seems associated with depressive symptoms in schizophrenia. • Network analyses were used to explore this association in a large sample. • Insight was associated with self-depreciation, guilt, and suicidal ideation. • Although cross-sectional, data suggest causal direction from insight to depression.

AbstractBackground:Patients with schizophrenia display experiential anomalies in their feelings and cognitions arising in the domain of their lived body. These abnormal bodily phenomena (ABP) are not part of diagnostic criteria for schizophrenia. One of the reasons is the difficulty to assess specific ABP for schizophrenia spectrum disorders. The present study aimed to explore the presence in patients with schizophrenia of specific ABP.Methods:We used a semistructured interview—the Abnormal Bodily Phenomena questionnaire (ABPq), an instrument devised to detect and measure ABP specific to patients with schizophrenia. Fifty-one outpatients affected by schizophrenia and 28 euthymic outpatients affected by bipolar disorder type I with psychotic features (BD-pf-e) were recruited. Before assessing the specificity for schizophrenia of the observed ABP, we tested the internal consistency and the convergent validity of the ABPq in patients with schizophrenia. Specificity was assessed by examining potential differences in ABPq among the patients with schizophrenia in remission (SCZ-r) and BD-pf-e.Results:The ABPq shows strong internal consistency and convergent validity. As to the specificity, ABP measured by ABPq were more frequent and severe in SCZ-r than in BD-pf-e. In particular, all ABPq dimensions, except “Coherence,” had at least mild severity in over 50% of SCZ-r, while dimensions with at least mild severity were observed in 5–10% of the BD-pf-e.Conclusions:These findings can contribute to establish more precise phenomenal boundaries between schizophrenia and bipolar disorder, to explore the borders between nonpsychotic and psychotic forms of ABP, between ABP and negative and disorganized symptoms, and to enlighten core aspects of schizophrenia.

AbstractBackground:The Bulgarian Ministry of Health invited the European Psychiatric Association (EPA) to evaluate Bulgarian mental health care service provision in 2018. Bulgarian mental health services face very significant challenges including a legacy of historic underfunding, internal conflicts, poor planning, and the emigration of very high numbers of younger skilled staff that had followed accession to the European Union. There were significant disputes between stakeholders regarding the way forward and had been at least two unsuccessful previous external agency interventions that had attempted to find solutions.Method:This EPA position paper describes in detail the EPA mission to Bulgaria including methodology, findings, recommendations, and finally the positive actions and changes that are now underway as a result of the EPA report and intervention aimed at contributing towards improving Bulgarian mental health services.Results:After meetings with multiple stakeholders in the Bulgarian mental health system and analysis of data on service delivery, workforce, funding and configuration the EPA Panel agreed a list of twenty recommendations for change.Conclusions:The EPA mission, with the collaboration of multiple stakeholders in Bulgaria, was successful in stimulating high level government action to improve mental health services. Despite longstanding differences, it was possible to involve the stakeholders in constructive dialogue. The importance of “speaking with one voice” was a key lesson learned.

AbstractBackground.Schizophrenia is a leading cause of disability. People living with schizophrenia (PLWS) present unemployment, social isolation, excess mortality and morbidity, and poor quality of life. Early recognition and appropriate treatment reduce the risk of chronicity and comorbidity. Personalization and integration of pharmacological and psychosocial interventions, as well as accurate identification and management of psychiatric and somatic comorbidities, can significantly improve mental and physical health of PLWS, promoting recovery.Methods.A three-step Delphi approach was used to explore consensus on the essential components of early recognition and intervention, personalization, and integration of care to improve schizophrenia outcome, and on barriers and challenges to close treatment gaps. The consensus involved 8 Italian experts of schizophrenia, 100 psychiatrists from academic and nonacademic settings, including representatives of Italian Society of Psychiatry, and 65 trainees in psychiatry.Results.A strong consensus (from mostly agree to totally agree) emerged on the importance of early diagnosis (97%), standardized assessments (91%), correct management of somatic and psychiatric comorbidities (99%), and personalization and integration of care (94%). Lack of time, human resources, and training were identified as the main barriers and challenges to the translation of knowledge into clinical practice.Conclusions.The results of this Delphi study demonstrated a strong consensus on main components of schizophrenia care, as well as on unmet needs to promote best practice and gaps between knowledge and clinical practice. The involvement of a large group of professionals and trainees in this in-depth consensus process might contribute to raise awareness and stimulate innovative strategies to improve the outcome of PLWS.

Background: The “Avolition-apathy” domain of the negative symptoms was found to include different symptoms by factor analytic studies on ratings derived by different scales. In particular, the relationship of anhedonia with this domain is controversial. Recently introduced negative symptom rating scales provide a better assessment of anhedonia, allowing the distinction of anticipatory and consummatory aspects, which might be related to different psychopathological dimensions. The study of associations with external validators, such as electrophysiological, brain imaging or cognitive indices, might shed further light on the status of anhedonia within the Avolition-apathy domain. Objectives: We used brain electrical microstates (MSs), which represent subsecond periods of quasi-stable scalp electrical field, associated with resting-state neural networks (and thus with global patterns of functional connectivity), to test whether the component symptoms of Avolition-apathy share the same correlates. Method: We analyzed multichannel resting EEGs in 142 individuals with schizophrenia (SCZ) and in 64 healthy controls (HC), recruited within the add-on EEG study of the Italian Network for Research on Psychoses. Relative time contribution, duration and occurrence of four MS classes (MS-A/-B/-C/−D) were calculated. Group differences on MS parameters (contribution and duration) and their associations with negative symptom domains (assessed using the Brief Negative Symptoms Scale) were investigated. Results: SCZ, in comparison to HC, showed increased contribution and duration of MS-C. The contribution of MS-A positively correlated with Avolition-apathy, but not with Expressive deficit. Within the Avolition-apathy domain, anticipatory anhedonia, avolition and asociality, but not consummatory anhedonia, showed the same correlations with MS-A contribution. Conclusion: Our findings support the existence of distinct electrophysiological correlates of Avolition-apathy with respect to Expressive deficit, and lend support to the hypothesis that only the anticipatory component of anhedonia shares the same pathophysiological underpinnings of the Avolition-apathy domain. Keywords: Schizophrenia, Avolition-apathy, Anhedonia, Resting-EEG, Brain electrical microstates

Neurocognitive deficits and negative symptoms (NS) have a pivotal role in subjects with schizophrenia (SCZ) due to their impact on patients’ functioning in everyday life and their influence on goal-directed behavior and decision-making. P3b is considered an optimal electrophysiological candidate biomarker of neurocognitive impairment for its association with the allocation of attentional resources to task-relevant stimuli, an important factor for efficient decision-making, as well as for motivation-related processes. Furthermore, associations between P3b deficits and NS have been reported. The current research aims to fill the lack of studies investigating, in the same subjects, the associations of P3b with multiple cognitive domains and the expressive and motivation-related domains of NS, evaluated with state-of-the-art instruments. One hundred and fourteen SCZ and 63 healthy controls (HCs) were included in the study. P3b amplitude was significantly reduced and P3b latency prolonged in SCZ as compared to HCs. In SCZ, a positive correlation was found between P3b latency and age and between P3b amplitude and the Attention-vigilance domain, while no significant correlations were found between P3b and the two NS domains. Our results indicate that the effortful allocation of attention to task-relevant stimuli, an important component of decision-making, is compromised in SCZ, independently of motivation deficits or other NS.

The present investigation explores the relationship between facial emotion recognition (FER) and symptom domains in three groups of schizophrenia spectrum patients (43 ultra-high-risk, 50 first episode and 44 multi-episode patients) in which the existence of FER impairment has already been demonstrated. Regression analysis showed that symptoms and FER impairment are related in multi-episode patients, regardless of the illness duration. We suggest that the link between symptoms and FER impairment is involved in the progression of the disease.