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Background: Negative symptoms of schizophrenia are correlated with reduction of normal function and lower quality of life. They were newly defined by the NIMH-MATRICS Consensus in 2005, dividing the rating tools to assess them into first-generation scales, developed before the Consensus, and second-generation scales, based on the recently introduced definitions., Methods: The COnsensus-based Standards for the selection of health Measurement Instrument (COSMIN) guidelines for systematic reviews were used to evaluate the quality of psychometric data of the first-generation scales that cover the 5 negative symptom domains of the NIMHS Consensus: the Scale for the Assessment of Negative Symptoms (SANS), the High Royds Evaluation of Negativity Scale (HEN), and the Negative Symptom Assessment-16 (NSA-16)., Results: The search strategy resulted in the inclusion of a total of 13 articles, 7 for the SANS, 4 for the NSA-16, and 2 for the HEN. For the SANS and the NSA-16, the overall results of the scales' measurement properties are mostly insufficient or indeterminate. The quality of evidence for the HEN is poor, due to a small number of validation studies/included patients., Conclusions: After applying the COSMIN guidelines, we do not recommend the usage of these first-generation scales to rate negative symptoms. At the minimum they require further validation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

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 < 65) and good outcome (GAF current ≥ 65). Pooled non-linear support vector machine (SVM) classifiers trained on the separate cohorts identified patients with a poor outcome with cross-validated balanced accuracies (BAC) of 65-66%, but BAC dropped substantially when the models were applied to patients from a different FES cohort (BAC = 50-56%). A leave-site-out analysis on the merged sample yielded better performance (BAC = 72%), highlighting the effect of combining data from different study designs to overcome calibration issues and improve model transportability. In conclusion, our results indicate that validation of prediction models in an independent sample is essential in assessing the true value of the model. Future external validation studies, as well as attempts to harmonize data collection across studies, are recommended., (© 2024. The Author(s).)

Psychiatry shares most ethical issues with other branches of medicine, but also faces special challenges. The Code of Ethics of the World Psychiatric Association offers guidance, but many mental health care professionals are unaware of it and the principles it supports. Furthermore, following codes of ethics is not always sufficient to address ethical dilemmas arising from possible clashes among their principles, and from continuing changes in knowledge, culture, attitudes, and socio-economic context. In this paper, we identify topics that pose difficult ethical challenges in contemporary psychiatry; that may have a significant impact on clinical practice, education and research activities; and that may require revision of the profession's codes of ethics. These include: the relationships between human rights and mental health care, research and training; human rights and mental health legislation; digital psychiatry; early intervention in psychiatry; end-of-life decisions by people with mental health conditions; conflicts of interests in clinical practice, training and research; and the role of people with lived experience and family/informal supporters in shaping the agenda of mental health care, policy, research and training. For each topic, we highlight the ethical concerns, suggest strategies to address them, call attention to the risks that these strategies entail, and highlight the gaps to be narrowed by further research. We conclude that, in order to effectively address current ethical challenges in psychiatry, we need to rethink policies, services, training, attitudes, research methods and codes of ethics, with the concurrent input of a range of stakeholders, open minded discussions, new models of care, and an adequate organizational capacity to roll-out the implementation across routine clinical care contexts, training and research., (© 2024 World Psychiatric Association.)

Schizophrenia is a severe psychiatric disorder, associated with a reduction in life expectancy of 15-20 years. Available treatments are at least partially effective in most affected individuals, and personal resources such as resilience (successful adaptation despite adversity) and coping abilities (strategies used to deal with stressful or threatening situations), are important determinants of disease outcomes and long-term sustained recovery. Published findings support the existence of a genetic background underlying resilience and coping, with variable heritability estimates. However, genome-wide analyses concerning the genetic determinants of these personal resources, especially in the context of schizophrenia, are lacking. Here, we performed a genome-wide association study coupled with accessory analyses to investigate potential genetic determinants of resilience, coping and self-esteem in 490 schizophrenia patients. Results revealed a complex genetic background partly overlapping with that of neuroticism, worry and schizophrenia itself and support the importance of social aspects in shapingthese psychological constructs. Hippocampal neurogenesis and lipid metabolism appear to be potentially relevant biological underpinnings, and specific miRNAs such as miR-124 and miR-137 may warrant further studies as potential biomarkers. In conclusion, this study represents an important first step in the identification of genetic and biological correlates shaping resilience, coping resources and self-esteem in schizophrenia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

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., (© 2024. The Author(s).)

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.

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., Competing Interests: SB received advisory board, lecture, or consulting fees, outside the present work, from: Angelini, Janssen Pharmaceuticals, Lundbeck, Otsuka. RC received advisory board fees from Boehringer and was a speaker for Rovi. SG reports consulting fees from Gedeon Richter; honoraria from Angelini, Boehringer Ingelheim, Gedeon Richter, Janssen, Lundbeck, Otsuka, Recordati, Rovi; and participation on data safety monitoring boards with Angelini, Boehringer Ingelheim, Janssen, and Rovi. AM received advisory board or consultant fees from the following drug companies: Angelini, Rovi and Boehringer Ingelheim outside the submitted work. MR has received compensation as speaker/consultant from Angelini, Lundbeck, Otzuka, Sumitomo Pharma, and Sunovion, and he has received research grants from Sumitomo Pharma. PR has received honoraria as consultant for lectures from Angelini, Janssen, Lundbeck, and Otsuka. Furthermore, she is in the advisory board of Angelini. AV received advisory board, lecture, or consulting fees, outside the present work, from: Angelini, Innova Pharma-Recordati, Janssen Pharmaceuticals, Lundbeck, Otsuka, and Pfizer. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Vita, Barlati, Cavallaro, Mucci, Riva, Rocca, Rossi and Galderisi.)

The Cognitive Assessment Interview (CAI) is an interview-based scale measuring cognitive impairment and its impact on functioning in subjects with schizophrenia (SCZ). The present study aimed at assessing, in a large sample of SCZ (n = 601), the agreement between patients and their informants on CAI ratings, to explore patients' insight in their cognitive deficits and its relationships with clinical and functional indices. Agreement between patient- and informant-based ratings was assessed by the Gwet's agreement coefficient. Predictors of insight in cognitive deficits were explored by stepwise multiple regression analyses. Patients reported lower severity of cognitive impairment vs. informants. A substantial to almost perfect agreement was observed between patients' and informants' ratings. Lower insight in cognitive deficits was associated to greater severity of neurocognitive impairment and positive symptoms, lower severity of depressive symptoms, and older age. Worse real-life functioning was associated to lower insight in cognitive deficit, worse neurocognitive performance, and worse functional capacity. Our findings indicate that the CAI is a valid co-primary measure with the interview to patients providing a reliable assessment of their cognitive deficits. In the absence of informants with good knowledge of the subject, the interview to the patient may represent a valid alternative., (© 2023. The Author(s).)

The Cognitive Assessment Interview (CAI) is an interview-based scale measuring cognitive impairment and its impact on functioning in subjects with schizophrenia (SCZ). It is approved as a coprimary measure of performance-based instruments, such as the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB). Recent research highlights negative symptoms, social cognition, and functional capacity as mediators of cognitive impairment's impact on functioning. This study compared mediation analysis outcomes using CAI or MCCB scores, providing insights into the utility of interview-based tools in research and clinical practice. The study included 618 individuals diagnosed with schizophrenia, recruited from 24 Italian psychiatric clinics. Neurocognitive assessments utilized both CAI and MCCB. Mediation analyses explored negative symptoms, social cognition, and functional capacity as mediators of the impact of neurocognition on real-life functioning domains. The study's results extend the validation of the CAI as a coprimary measure that provides valid information on the impact of cognitive impairment on real-life functioning and its possible mediators, complementing the information obtained using the MCCB. Interview-based cognitive assessment might be essential for understanding schizophrenia complexity and its impact on various cognitive and functional domains for clinicians, patients, and caregivers., (© The Author(s) 2024. Published by Oxford University Press on behalf of the University of Maryland's school of medicine, Maryland Psychiatric Research Center.)

Background: The 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., Methods: Sixty-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., Results: Attention/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., Conclusion: Neurocognitive 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Giuliani, Pezzella, Giordano, Fazio, Mucci, Perrottelli, Blasi, Amore, Rocca, Rossi, Bertolino, Galderisi and Maj.)

Deficits in N-methyl-d-aspartate receptor (NMDAR) signaling are implicated in the pathogenesis of schizophrenia. Luvadaxistat (TAK-831/NBI-1065844) is an investigational d-amino acid oxidase (DAAO) inhibitor that increases d-serine levels at NMDAR coagonist sites. INTERACT is a phase 2 randomized, placebo-controlled study that evaluated the efficacy and safety of three doses of luvadaxistat, covering a range of DAAO occupancy and d-serine levels, in patients with schizophrenia with persistent negative symptoms. The study included a 14-day, single-blinded placebo run-in period and a 12-week, double-blinded treatment period. The primary efficacy endpoint was the 12-week change from baseline in Positive and Negative Syndrome Scale-Negative Symptom Factor Score (PANSS NSFS). Secondary efficacy endpoints included the 12-week changes from baseline in Brief Assessment of Cognition in Schizophrenia (BACS) score and Schizophrenia Cognition Rating Scale (SCoRS) score. Safety endpoints included adverse event assessments. The full analysis set included all randomized patients (N = 256 [placebo, n = 87; luvadaxistat 50 mg, n = 58; 125 mg, n = 56; 500 mg, n = 55]); 228 patients completed the study. No significant improvements in PANSS NSFS were observed at any dose versus placebo at week 12. Improvements were observed with luvadaxistat 50 mg versus placebo in cognitive endpoints: BACS composite score (nominal one-sided p = 0.031) and SCoRS interviewer total score (nominal one-sided p = 0.011). Luvadaxistat did not significantly improve negative symptoms of schizophrenia. However, luvadaxistat 50 mg met the prespecified secondary endpoints for cognitive performance (BACS) and function (SCoRS), warranting further investigation in patients with cognitive impairment associated with schizophrenia. Luvadaxistat was well-tolerated in INTERACT, with no new safety signals observed. ClinicalTrials.gov: NCT03382639., Competing Interests: Declaration of competing interest VM, EH, MA, and CD are employees of Takeda Pharmaceutical Company Limited, and own stock or stock options. ND, RE, and ER are former employees of Takeda Pharmaceutical Company Limited. TG and JS are employees of Neurocrine Biosciences, Inc. ED is an employee of Neurocrine Biosciences, Inc., and a former employee of Takeda Pharmaceutical Company Limited. SG received compensation for serving as a consultant or speaker, or she or the institutions she works for have received research support from the companies or organizations indicated: Angelini, Gedeon Richter-Recordati, Innova Pharma-Recordati Group, Janssen Cilag, Janssen Pharmaceutica NV, Lundbeck Italia, Rovi and Recordati Pharmaceuticals., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Hypothesis: Negative symptoms are very important for the overall loss of functioning observed in patients with schizophrenia. There is a need for valid tools to assess these symptoms., Study Design: We used the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) systematic review guideline to evaluate the quality of the clinical assessment interview for negative symptoms (CAINS) as a clinician-rated outcome measurement (ClinROM)., Study Results: The search strategy resulted in the retrieval of 13 articles, 11 of which were included in this evaluation. In terms of risk of bias, most articles reported on measures of internal consistency and construct validity, which were overall of good quality. Structural validity, reliability, measurement error, and cross-cultural validity were reported with less than optimum quality. There was a risk of bias in ClinROM development. According to the updated criteria of good measurement properties, structural validity, internal consistency, and reliability showed good results. In contrast, hypothesis testing was somewhat poorer. Results for cross-cultural validity were indeterminate. According to the updated GRADE approach from the COSMIN group the scale received a moderate grade., Conclusions: The COSMIN standard allows a judgment of the CAINS as an instrument with the potential to be recommended for use, but which requires further research to assess its quality, in particular in the domains of content validity, internal consistency, and cross-cultural validity., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

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.

Deficits in social cognition (SC) interfere with recovery in schizophrenia (SZ) and may be related to resting state brain connectivity. This study aimed at assessing the alterations in the relationship between resting state functional connectivity and the social-cognitive abilities of patients with SZ compared to healthy subjects. We divided the brain into 246 regions of interest (ROI) following the Human Healthy Volunteers Brainnetome Atlas. For each participant, we calculated the resting-state functional connectivity (rsFC) in terms of degree centrality (DC), which evaluates the total strength of the most powerful coactivations of every ROI with all other ROIs during rest. The rs-DC of the ROIs was correlated with five measures of SC assessing emotion processing and mentalizing in 45 healthy volunteers (HVs) chosen as a normative sample. Then, controlling for symptoms severity, we verified whether these significant associations were altered, i.e., absent or of opposite sign, in 55 patients with SZ. We found five significant differences between SZ patients and HVs: in the patients' group, the correlations between emotion recognition tasks and rsFC of the right entorhinal cortex (R-EC), left superior parietal lobule (L-SPL), right caudal hippocampus (R-c-Hipp), and the right caudal (R-c) and left rostral (L-r) middle temporal gyri (MTG) were lost. An altered resting state functional connectivity of the L-SPL, R-EC, R-c-Hipp, and bilateral MTG in patients with SZ may be associated with impaired emotion recognition. If confirmed, these results may enhance the development of non-invasive brain stimulation interventions targeting those cerebral regions to reduce SC deficit in SZ., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Approximately 8 % of patients with schizophrenia are diagnosed before age 18, and 18 % experience their first symptoms before age 18. This narrative review explores the management of patients with early-onset schizophrenia (EOS) and childhood-onset schizophrenia (COS) from diagnosis to their transition to adult care settings. Early diagnosis of schizophrenia in children and adolescents is essential for improving outcomes, but delays are common due to overlapping of symptoms with developmental phenomena and other psychiatric conditions, including substance use, and lack of clinicians' awareness. Once diagnosed, antipsychotic treatment is key, with specific second-generation agents generally being preferred due to better tolerability and their broader efficacy evidence-base in youth. Dosing should be carefully individualized, considering age-related differences in drug metabolism and side effect liability. Clinicians must be vigilant in detecting early non-response and consider switching or dose escalation when appropriate. Since early age of illness onset is a consistent risk factor for treatment-resistant schizophrenia (TRS), clinicians need to be competent in diagnosing TRS and using clozapine. Since COS and EOS are associated with cognitive deficits and impaired functioning, psychosocial interventions should be considered to improve overall functioning and quality of life. Good long-term outcomes depend on continuous treatment engagement, and successful transitioning from pediatric to adult care requires careful planning, early preparation, and collaboration between pediatric and adult clinicians. Targeting functional outcomes and quality of life in addition to symptom remission can improve overall patient well-being. Comprehensive evaluations, age-specific assessments, and targeted interventions are needed to address the unique challenges of EOS and COS., Competing Interests: Declaration of competing interest CU Correll has been a consultant and/or advisor to or has received honoraria from: AbbVie, Acadia, Alkermes, Allergan, Angelini, Aristo, Biogen, Boehringer-Ingelheim, Cardio Diagnostics, Cerevel, CNX Therapeutics, Compass Pathways, Darnitsa, Denovo, Gedeon Richter, Hikma, Holmusk, IntraCellular Therapies, Jamjoom Pharma, Janssen/J&J, Karuna, LB Pharma, Lundbeck, MedAvante-ProPhase, MedInCell, Merck, Mindpax, Mitsubishi Tanabe Pharma, Mylan, Neurocrine, Neurelis, Newron, Noven, Novo Nordisk, Otsuka, Pharmabrain, PPD Biotech, Recordati, Relmada, Reviva, Rovi, Sage, Seqirus, SK Life Science, Sunovion, Sun Pharma, Supernus, Takeda, Teva, Tolmar, and Viatris. He provided expert testimony for Janssen and Otsuka. He served on a Data Safety Monitoring Board for Compass Pathways, Denovo, Lundbeck, Relmada, Reviva, Rovi, Supernus, and Teva. He has received grant support from Janssen and Takeda. He received royalties from UpToDate and is also a stock option holder of Cardio Diagnostics, Kuleon Biosciences, LB Pharma, Mindpax, and Quantic. C. Arango has been a consultant to or has received honoraria or grants from Acadia, Angelini, Biogen, Boehringer, Gedeon Richter, Janssen Cilag, Lundbeck, Medscape, Menarini, Minerva, Otsuka, Pfizer, Roche, Sage, Servier, Shire, Schering Plough, Sumitomo Dainippon Pharma, Sunovion and Takeda. B Fagerlund declares travel expenses and writing assistance for the submitted work, funded by Angelini. S Galderisi has received personal fees from Angelini Pharma, Boehringer Ingelheim, Gedeon Richter-Recordati, Janssen, Lundbeck, Otsuka, Recordati Pharmaceuticals, Rovi Pharma, Sunovion Pharmaceuticals, outside the submitted work. MJ Kas has received (non-related) research funding from Novartis. In the last 3 years, he has received fees for lectures from Angelini and Boehringer Ingelheim. S Leucht has been an advisor and/or lecturer and/or has developed educational material for Alkermes, Angelini, Apsen, Eisai, Gedeon Richter, Janssen, Karuna, Kynexis, Lundbeck, Medichem, Medscape, Merck Sharpp and Dome, Mitshubishi, Neurotorium, NovoNordisk, Otsuka, Recordati, Roche, Rovi, Sanofi Aventis, TEVA., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: We examined the course of illness over a 12-month period in a large, international multi-center cohort of people with a first-episode schizophrenia spectrum disorder (FES) in a naturalistic, prospective study (PSYSCAN)., Method: Patients with a first episode of schizophrenia, schizoaffective disorder (depressive type) or schizophreniform disorder were recruited at 16 institutions in Europe, Israel and Australia. Participants (N = 304) received clinical treatment as usual throughout the study., Results: The mean age of the cohort was 24.3 years (SD = 5.6), and 67 % were male. At baseline, participants presented with a range of intensities of psychotic symptoms, 80 % were taking antipsychotic medication, 68 % were receiving psychological treatment, with 46.5 % in symptomatic remission. The mean duration of untreated psychosis was 6.2 months (SD = 17.0). After one year, 67 % were in symptomatic remission and 61 % were in functional remission, but 31 % had been readmitted to hospital at some time after baseline. In the cohort as a whole, depressive symptoms remained stable over the follow-up period. In patients with a current depressive episode at baseline, depressive symptoms slightly improved. Alcohol, tobacco and cannabis were the most commonly used substances, with daily users of cannabis ranging between 9 and 11 % throughout the follow-up period., Conclusions: This study provides valuable insight into the early course of a broad range of clinical and functional aspects of illness in FES patients in routine clinical practice., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Arango has been a consultant to or has received honoraria or grants from Acadia, Angelini, Biogen, Boehringer, Gedeon Richter, Janssen Cilag, Lundbeck, Medscape, Menarini, Minerva, Otsuka, Pfizer, Roche, Sage, Servier, Shire, Schering Plough, Sumitomo Dainippon Pharma, Sunovion and Takeda. Dr. Glenthøj has been the leader of a Lundbeck Foundation Centre of Excellence for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS) (January 2009 – December 2021), which was partially financed by an independent grant from the Lundbeck Foundation based on international review and partially financed by the Mental Health Services in the Capital Region of Denmark, the University of Copenhagen, and other foundations. All grants are the property of the Mental Health Services in the Capital Region of Denmark and administrated by them. She has no other conflicts to disclose. Dr. Sachs has been a consultant to or has received honoraria from Angelini, Janssen Cilag, Lundbeck, Mylan, Recordati. The other authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

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., Competing Interests: The following conflicts of interest are declared: Robert A. McCutcheon has received speaker/consultancy fees from Karuna, Janssen, Boehringer Ingelheim, and Otsuka, and co-directs a company that designs digital resources to support treatment of mental illness. Gemma Modinos has received consultancy fees from Boehringer Ingelheim for work unrelated to this study. Silvana Galderisi received advisory board/consultant fees, or honoraria/expenses from the following drug companies: Angelini, Boehringer Ingelheim, Gedeon Richter-Recordati, Innova Pharma-Recordati Group, Janssen, Lundbeck, Otsuka, Recordati Pharmaceuticals, Rovi Pharma and Sunovion Pharmaceuticals outside the submitted work., (© 2024 Published by Elsevier Inc.)

The pathophysiology of schizophrenia and bipolar disorder involves a complex interaction between genetic and environmental factors that begins in the early stages of neurodevelopment. Recent advancements in the field of induced pluripotent stem cells (iPSCs) offer a promising tool for understanding the neurobiological alterations involved in these disorders and, potentially, for developing new treatment options. In this review, we summarize the results of iPSC-based research on schizophrenia and bipolar disorder, showing disturbances in neurodevelopmental processes, imbalance in glutamatergic-GABAergic transmission and neuromorphological alterations. The limitations of the reviewed literature are also highlighted, particularly the methodological heterogeneity of the studies, the limited number of studies developing iPSC models of both diseases simultaneously, and the lack of in-depth clinical characterization of the included samples. Further studies are needed to advance knowledge on the common and disease-specific pathophysiological features of schizophrenia and bipolar disorder and to promote the development of new treatment options., Competing Interests: Competing interests:: Silvana Galderisi reports consulting fees from Gedeon Richter; honoraria from Angelini, Boehringer Ingelheim, Gedeon Richter, Janssen, Lundbeck, Otsuka, Recordati, Rovi, and Sunovion; and participation on data safety monitoring boards with Angelini, Boehringer Ingelheim, Janssen, and Rovi. Giulia Maria Giordano reports consulting fees from Angelini. Armida Mucci reports consulting fees from Pierre Fabre, Rovi, and Boehringer Ingelheim; patents with Pierre Fabre; and participation on data safety monitoring boards with Angelini and Boehringer Ingelheim. No other competing interests were declared., (© 2024 CMA Impact Inc. or its licensors.)

Cognitive impairment (CI) is regarded as a remarkable burden in COVID-19 survivors. Its prevalence and profile, and relationships with the disease clinical and laboratory indices, remain unclear. The present study investigated, in a large sample of patients recovered from COVID-19, the frequency of CI with both a face-to-face screening tool and comprehensive test battery (MCCB). The study also evaluated the profile of CI and its relationships with COVID-19 clinical and laboratory indices and with psychopathological features. Out of 1344 subjects assessed for eligibility, 736 completed the screening phase 11 months after the COVID-19 infection; 402 participated in the baseline phase and completed an in depth cognitive, clinical and laboratory assessment about one month later. More than one third of the screened subjects presented a CI (COG+); it was associated to age, education, male gender, COVID-19 severity, and presence of anosmia, dyspnea at rest and exertional dyspnea during the acute phase. COG+ subjects showed a higher severity of depression, anxiety and post-traumatic distress, and worse global functioning, than subjects without CI. The MCCB showed that 45% of the subjects had a CI involving attention, working memory, verbal learning, visual learning, and reasoning and problem solving. Finally, neurocognitive functioning was inversely correlated with LDH blood levels, a potential biomarker of disease severity. According to our findings, cognitive functioning should be routinely and periodically assessed in COVID-19 patients, especially in older subjects, who experienced more severe COVID-19 symptoms. In case of persisting dysfunctions cognitive training programs should be considered as treatment strategies., Competing Interests: Declaration of Competing Interest Prof. Silvana Galderisi, in the last three years, received advisory board/consultant fees, or honoraria/expenses from the following drug companies: Angelini, Boehringer Ingelheim, Gedeon Richter-Recordati, Janssen, Lundbeck, Otsuka, Recordati Pharmaceuticals, Rovi Pharma, Sunovion Pharmaceuticals. Prof. Antonio Vita, in the last three years, received advisory board/consultant fees and support for clinical studies or trials, conferences, and congress presentations from the following drug companies: Alkermes, Angelini, Boehringer Ingelheim, Janssen- Cilag, Lundbeck, Otsuka, Roche, Rovi Pharma. Prof. Armida Mucci, in the last three years, received advisory board/consultant fees from the following drug companies: Angelini, Boehringer Ingelheim, Pierre Fabre and Rovi Pharma. Prof. Stefano Barlati, in the last three years, received advisory board/consultant fees and support for clinical studies or trials, conferences, and congress presentations from the following drug companies: Angelini, Lundbeck, and Otsuka. All other authors have no conflicts of interest to declare., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: In 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., Methods: The 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., Results: One 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., Conclusions: Our 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., Competing Interests: GG has been a consultant for Angelini. AM has been a consultant and/or advisor to or has received honoraria from Angelini, Gedeon. Richter Bulgaria, Janssen Pharmaceuticals, Lundbeck, Otsuka Pharmaceutical, Pfizer, Pierre Fabre, Rovi. Pharma and Boehringer Ingelheim. AE received consulting fees and/or honoraria for speeches within the last 3 years from Angelini, AOP Orphan, Germania, Janssen, Krka, Lundbeck, Mylan, Neuraxpharm, Recordati, and Sandoz. BG has been the leader of a Lundbeck Foundation Centre of Excellence for Clinical Intervention and Neuropsychiatric Schizophrenia Research CINS January 2009 – December 2021, which was partially financed by an independent grant from the Lundbeck Foundation based on international review and partially financed by the Mental Health Services in the Capital Region of Denmark, the University of Copenhagen, and other foundations. All grants are the property of the Mental Health Services in the Capital Region of Denmark and administrated by them. She has no other conflicts to disclose. AH has been a consultant for Recordati and Boehringer Ingelheim and Newron Pharmaceuticals and participated in educational conferences for Janssen and Lundbeck. JH received consulting fees and/or honoraria for speeches within the last 3 years from Angelini, Lundbeck, Janssen and Servier. SG has been a consultant and/or advisor to or has received honoraria from Angelini, Boehringer Ingelheim, Gedeon Richter-Recordati, Innova Pharma-Recordati Group, Janssen, Lundbeck, Otsuka, Recordati Pharmaceuticals, Rovi Pharma and Sunovion Pharmaceuticals. GS is president of the Austrian Society of Neuropsychopharmacology and Biological Psychiatry, which is partially financed by the support from pharmaceutical companies. GS received consulting fees and/or honoraria for speeches within the last 3 years from Janssen, Lundbeck, Mylan, Recordati, and Schwabe. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer CM declared a past co-authorship with the authors AM and SG to the handling editor. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Giordano, Pezzella, Mucci, Austin, Erfurth, Glenthøj, Hofer, Hubenak, Libiger, Melle, Nielsen, Rybakowski, Wojciak, Galderisi and Sachs.)

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.

Dis-sociality (DS) reflects the impairment of social experience in people with schizophrenia; it encompasses both negative features (disorder of attunement, inability to grasp the meaning of social contexts, the vanishing of social shared knowledge) and positive features (a peculiar set of values, ruminations not oriented to reality), reflecting the existential arrangement of people with schizophrenia. DS is grounded on the notion of schizophrenic autism as depicted by continental psychopathology. A rating scale has been developed, providing an experiential phenotype. Here we present the Autism Rating Scale for Schizophrenia - Revised English version (ARSS-Rev), developed on the Italian version of the scale. The scale is provided by a structured interview to facilitate the assessment of the phenomena investigated here. ARSS-Rev is composed of 16 distinctive items grouped into 6 categories: hypo-attunement, invasiveness, emotional flooding, algorithmic conception of sociality, antithetical attitude toward sociality, and idionomia. For each item and category, an accurate description is provided. Different intensities of phenomena are assessed through a Likert scale by rating each item according to its quantitative features (frequency, intensity, impairment, and need for coping). The ARSS-Rev has been able to discriminate patients with remitted schizophrenia from euthymic patients with psychotic bipolar disorder. This instrument may be useful in clinical/research settings to demarcate the boundaries of schizophrenia spectrum disorders from affective psychoses., (© 2023 S. Karger AG, Basel.)