Advances in the understanding of the pathophysiology of schizophrenia and bipolar disorder through induced pluripotent stem cell models.

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.

Safety of electroconvulsive therapy (ECT) in pregnancy: a systematic review of case reports and case series.

Pregnancy and the immediate postpartum period are considered at high risk for women who have already received a previous psychiatric diagnosis and might represent a stressful event favoring the onset of new psychiatric disorders. The electroconvulsive therapy (ECT) is effective for the treatment of severe, treatment-resistant mental disorders, and it could represent a therapeutic choice for psychiatric conditions during pregnancy. The purpose of this systematic review is to evaluate the safety of ECT during pregnancy and to update the state of the art of its use. An extensive literature search on PubMed, APA PsycInfo, and Scopus databases for relevant articles published from inception to September 2023 has been performed. A final number of 45 articles (34 case reports and 11 case series, for a total of 130 pregnant women) were included in the present review. The limited evidence confirmed that ECT is effective in determining a partial remission of symptoms in women suffering from severe mental disorders, especially in the presence of suicidal ideation or psychosis, during all pregnancy epochs. However, ECT is not free from side effects, although the majority of possible complications were of low- or moderate-grade and not life-threatening for the women. Exposure to pharmacological treatment before or during the ECT or to the anesthetic during ECT might have contributed to the onset of these complications. ECT techniques evolved over years, increasing the degree of its safety, and according to our review it appears to be relatively safe and effective during pregnancy in the majority of cases.

Clinical and psychological factors associated with resilience in patients with schizophrenia: data from the Italian network for research on psychoses using machine learning.

BACKGROUND: Resilience is defined as the ability to modify thoughts to cope with stressful events. Patients with schizophrenia (SCZ) having higher resilience (HR) levels show less severe symptoms and better real-life functioning. However, the clinical factors contributing to determine resilience levels in patients remain unclear. Thus, based on psychological, historical, clinical and environmental variables, we built a supervised machine learning algorithm to classify patients with HR or lower resilience (LR). METHODS: SCZ from the Italian Network for Research on Psychoses (N = 598 in the Discovery sample, N = 298 in the Validation sample) underwent historical, clinical, psychological, environmental and resilience assessments. A Support Vector Machine algorithm (based on 85 variables extracted from the above-mentioned assessments) was built in the Discovery sample, and replicated in the Validation sample, to classify between HR and LR patients, within a nested, Leave-Site-Out Cross-Validation framework. We then investigated whether algorithm decision scores were associated with the cognitive and clinical characteristics of patients. RESULTS: The algorithm classified patients as HR or LR with a Balanced Accuracy of 74.5% (p < 0.0001) in the Discovery sample, and 80.2% in the Validation sample. Higher self-esteem, larger social network and use of adaptive coping strategies were the variables most frequently chosen by the algorithm to generate decisions. Correlations between algorithm decision scores, socio-cognitive abilities, and symptom severity were significant (pFDR < 0.05). CONCLUSIONS: We identified an accurate, meaningful and generalizable clinical-psychological signature associated with resilience in SCZ. This study delivers relevant information regarding psychological and clinical factors that non-pharmacological interventions could target in schizophrenia.

Die "Präzisionspsychiatrie" muss Teil der "personalisierten Psychiatrie" werden.

'Precision medicine' is defined as 'an emerging approach for treatment and prevention that takes into account each person's variability in genes, environment, and lifestyle'. Sometimes the term 'personalized medicine' is also used, either as a synonym or in a broader sense. In psychiatry, the term 'personalized' applies to different levels of health-care provision, such as the service organization and the choice of treatment plans based on the characterization of the individual patient. This approach is already feasible but, currently, it is often hampered by the shortage of human and financial resources. Recently, the terminology of 'precision medicine' has been extended to psychiatry: the term 'precision psychiatry' refers to the full exploitation of recent scientific and technological advances to achieve a close match between individual biosignature and prevention / treatment strategies. This article provides an overview of recent advances in neuroimaging, multi-omics and computational neuroscience, which have contributed to foster our understanding of the neurobiology of major mental disorders, and led to the implementation of a precision medicine-oriented approach in psychiatry.We argue that, while 'precision psychiatry' represents an important step to further advance the effectiveness of the 'personalized psychiatry', the distinction between the two terms is important to avoid dangerous neglect of the current potential of personalized care in psychiatry and to underscore the need for disseminating good existing practices aimed at organizing mental health services and providing care according to person's psychopathological characteristics, illness trajectory, needs, environment and preferences.In conclusion, 'precision psychiatry' will contribute to advance 'personalized psychiatry', but for the time being keeping the distinction between the two terms will contribute to fully exploit the current potential of personalized care.

Understanding the Pathophysiology of Mental Diseases and Early Diagnosis Thanks to Electrophysiological Tools: Some Insights and Empirical Facts.

Objective. Neurophysiological tools remain indispensable instruments in the assessment of psychiatric disorders. These techniques are widely available, inexpensive and well tolerated, providing access to the assessment of brain functional alterations. In the clinical psychiatric context, electrophysiological techniques are required to provide important information on brain function. While there is an immediate benefit in the clinical application of these techniques in the daily routine (emergency assessments, exclusion of organic brain alterations), these tools are also useful in monitoring the progress of psychiatric disorders or the effects of therapy. There is increasing evidence and convincing literature to confirm that electroencephalography and related techniques can contribute to the diagnostic workup, to the identification of subgroups of disease categories, to the assessment of long-term causes and to facilitate response predictions. Methods and Results. In this report we focus on 3 different novel developments of the use of neurophysiological techniques in 3 highly prevalent psychiatric disorders: (1) the value of EEG recordings and machine learning analyses (deep learning) in order to improve the diagnosis of dementia subtypes; (2) the use of mismatch negativity in the early diagnosis of schizophrenia; and (3) the monitoring of addiction and the prevention of relapse using cognitive event-related potentials. Empirical evidence was presented. Conclusion. Such information emphasized the important role of neurophysiological tools in the identification of useful biological markers leading to a more efficient care management. The potential of the implementation of machine learning approaches together with the conduction of large cross-sectional and longitudinal studies was also discussed.

On the Road to Individualizing Pharmacotherapy for Adolescents and Adults with Schizophrenia - Results from an Expert Consensus Following the Delphi Method.

Introduction: Schizophrenia is a severe mental illness that usually begins in late adolescence or early adulthood. Current pharmacological treatments, while acceptably effective for many patients, are rarely clinically tailored or individualized. The lack of sufficient etiopathological knowledge of the disease, together with overall comparable effect sizes for efficacy between available antipsychotics and the absence of clinically actionable biomarkers, has hindered the advance of individualized medicine in the treatment of schizophrenia. Nevertheless, some degree of stratification based on clinical markers could guide treatment choices and help clinicians move toward individualized psychiatry. To this end, a panel of experts met to formally discuss the current approach to individualized treatment in schizophrenia and to define how treatment individualization could help improve clinical outcomes. Methods: A task force of seven experts iteratively developed, evaluated, and refined questionnaire items, which were then evaluated using the Delphi method. Descriptive statistics were used to summarize and rank expert responses. Expert discussion, informed by the results of a scoping review on personalizing the pharmacologic treatment of adults and adolescents with schizophrenia, ultimately generated recommendations to guide individualized pharmacologic treatment in this population. Results: There was substantial agreement among the expert group members, resulting in the following recommendations: 1) individualization of treatment requires consideration of the patient's diagnosis, clinical presentation, comorbidities, previous treatment response, drug tolerability, adherence patterns, and social factors; 2) patient preferences should be considered in a shared decision-making approach; 3) identified barriers to personalized care that need to be overcome include the lack of actionable biomarkers and mechanistic similarities between available treatments, but digital tools should be increasingly used to enhance individualized treatment. Conclusion: Individualized care can help provide effective, tailored treatments based on an individual's clinical characteristics, disease trajectory, family and social environment, and goals and preferences.

Finding the Right Setting for the Right Treatment During the Acute Treatment of Individuals with Schizophrenia: A Narrative Review and Clinical Practice Guideline.

Background: Schizophrenia is most times a chronic and often debilitating illness associated with poor mental health outcomes. Early and effective treatment of schizophrenia in the most appropriate setting can make a significant difference in the long-term recovery. The aim of this narrative review was to provide suggestions and recommendations for effectively managing patients with schizophrenia during acute exacerbations and to enhance awareness and skills related to personalized medicine. Methods: A panel of academics and clinicians with experience in the field of psychosis met virtually on July 13th 2023 to narratively review and discuss the research evidence and their clinical experience about the most appropriate acute treatments for patients with schizophrenia. This manuscript represents a synthesis of the panel analysis and discussion. Results: First contact is very important for service users, as is finding the most adequate treatment setting. If patients present to the emergency department, which may be a traumatic setting for service users, a dedicated environment with adequate space and specialized mental health support, including personnel trained in de-escalation techniques, is recommended. A well-connected continuum of care is strongly recommended, possibly with seamless links between inpatient units, day hospital services, outpatient facilities and rehabilitation services. Ideally, this should be structured as part of a coordinated step-down service line. Treatment challenges include suboptimal response, side effects, and nonadherence, which is reduced by the use of long-acting injectable antipsychotics. Conclusion: Individual circumstances, including age, gender, and presence of hostility/aggression or self-harm, cognitive impairment and negative symptoms, comorbidities (depression, substance use disorders) or associated symptoms (anxiety, insomnia), should be considered when selecting the most appropriate treatment for the acute phase of schizophrenia. Efficacy and feasibility, as well as acceptability and tolerability of treatments, require joint consideration from the early stages of schizophrenia, thereby enhancing the possibility of improved short- and long-term outcomes.

The relationship between the resting state functional connectivity and social cognition in schizophrenia: Results from the Italian Network for Research on Psychoses.

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.

The Brief negative Symptom Scale (BNSS): a systematic review of measurement properties.

BACKGROUND: Negative symptoms of schizophrenia are linked with poor functioning and quality of life. Therefore, appropriate measurement tools to assess negative symptoms are needed. The NIMH-MATRICS Consensus defined five domains for negative symptoms, which The Brief Negative Symptom Scale (BNSS) covers. METHODS: We used the COSMIN guidelines for systematic reviews to evaluate the quality of psychometric data of the BNSS scale as a Clinician-Rated Outcome Measure (ClinROM). RESULTS: The search strategy resulted in the inclusion of 17 articles. When using the risk of bias checklist, there was a generally good quality in reporting of structural validity and hypothesis testing. Internal consistency, reliability and cross-cultural validity were of poorer quality. ClinROM development and content validity showed inadequate results. According to the updated criteria of good measurement properties, structural validity, internal consistency and interrater reliability showed good results, while hypothesis testing showed poorer results. Cross-cultural validity and test-retest reliability were indeterminate. The updated GRADE approach resulted in a moderate grade. CONCLUSIONS: We can potentially recommend the use of the BNSS as a concise tool to rate negative symptoms. Due to weaknesses in certain domains further validations are warranted.

Correlations between Negative Symptoms and Cognitive Deficits in Individuals at First Psychotic Episode or at High Risk of Psychosis: A Systematic Review.

The present review aims to identify correlations between negative symptoms (NS) and deficits in neurocognition and social cognition in subjects with first-episode psychosis (FEP) and at-high-risk populations (HR). A systematic search of the literature published between 1 January 2005 and 31 December 2022 was conducted on PubMed, Scopus, and PsycInfo. Out of the 4599 records identified, a total of 32 studies met our inclusion/exclusion criteria. Data on a total of 3086 FEP and 1732 HR were collected. The available evidence shows that NS correlate with executive functioning and theory of mind deficits in FEP subjects, and with deficits in the processing speed, attention and vigilance, and working memory in HR subjects. Visual learning and memory do not correlate with NS in either FEP or HR subjects. More inconsistent findings were retrieved in relation to other cognitive domains in both samples. The available evidence is limited by sample and methodological heterogeneity across studies and was rated as poor or average quality for the majority of included studies in both FEP and CHR populations. Further research based on shared definitions of first-episode psychosis and at-risk states, as well as on more recent conceptualizations of negative symptoms and cognitive impairment, is highly needed.

Resting-State Brain Activity Dysfunctions in Schizophrenia and Their Associations with Negative Symptom Domains: An fMRI Study.

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.

A multivariate approach to investigate the associations of electrophysiological indices with schizophrenia clinical and functional outcome.

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.

Social cognition and real-life functioning in patient samples with 22q11.2 deletion syndrome with or without psychosis, compared to a large sample of patients with schizophrenia only and healthy controls.

Patients with the 22q11.2 deletion syndrome (DS) show an increased risk of developing a psychotic illness lifetime. 22q11.2DS may represent a reliable model for studying the neurobiological underpinnings of schizophrenia. The study of social inference abilities in a genetic condition at high risk for psychosis, like 22q11.2DS, may shed light on the relationships between neurocognitive processes and patients' daily general functioning. The study sample consisted of 1736 participants, divided into four groups: 22q11.2DS patients with diagnosis of psychotic disorder (DEL SCZ, N = 20); 22q11.2DS subjects with no diagnosis of psychosis (DEL, N = 43); patients diagnosed with schizophrenia without 22q11.2DS (SCZ, N = 893); and healthy controls (HC, N = 780). Social cognition was assessed through The Awareness of Social Inference Test (TASIT) and general functioning through the Specific Levels of Functioning (SLoF) scale. We analysed data through regression analysis. The SCZ and DEL groups had similar levels of global functioning; they both had significantly lower SLoF Total scores than HC (p < .001); the DEL SCZ group showed significantly lower scores compared to the other groups (SCZ, p = .004; DEL, p = .003; HC, p < .001). A significant deficit in social cognition was observed in the three clinical groups. In the DEL SCZ and SCZ groups, TASIT scores significantly predicted global functioning (p < .05). Our findings of social cognition deficit in psychosis-prone patients point to the possible future adoption of rehabilitation programmes, like Social Skills Training and Cognitive Remediation, during premorbid stages of psychosis.

Does social cognition change? Evidence after 4 years from the Italian Network for Research on Psychoses.

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.

Sex and gender differences in clinical and functional indices in subjects with schizophrenia and healthy controls: Data from the baseline and 4-year follow-up studies of the Italian Network for Research on Psychoses.

Gender differences in clinical and psychosocial aspects of schizophrenia have been widely reported. Findings have not always been consistent, and some of them need further research. In a large sample of community dwelling persons with schizophrenia, we investigated gender differences in clinical, cognitive and functional indices, as well as their changes over a 4-year follow-up and their impact on real-life functioning. Gender differences in personal resources, cognitive and functional indices were explored also in a sample of healthy controls. Men with respect to women had an earlier age of illness onset, a worse premorbid adjustment in the academic domain, more severe avolition, expressive deficit and positive symptoms, lower prevalence of comorbidity for affective disorders, less frequent use of two coping strategies ('religion' and 'use of emotional support') and more frequent positive history of substance and alcohol abuse. In addition, men were more impaired in verbal learning, while women in reasoning/problem solving. Some patterns of gender differences observed in healthy controls were not confirmed in patients. Men's disadvantages in the clinical picture did not translate into a worse outcome. This finding may be related to the complex interplay of several factors acting as predictors or mediators of outcome.

Updated perspectives on the clinical significance of negative symptoms in patients with schizophrenia.

INTRODUCTION: Negative symptoms in schizophrenia are associated with poor response to available treatments, poor quality of life, and functional outcome. Therefore, they represent a substantial burden for people with schizophrenia, their families, and health-care systems. AREAS COVERED: In this manuscript, we will provide an update on the conceptualization, assessment, and treatment of this complex psychopathological dimension of schizophrenia. EXPERT OPINION: Despite the progress in the conceptualization of negative symptoms and in the development of state-of-the-art assessment instruments made in the last decades, these symptoms are still poorly recognized, and not always assessed in line with current conceptualization. Every effort should be made to disseminate the current knowledge on negative symptoms, on their assessment instruments and available treatments whose efficacy is supported by research evidence. Longitudinal studies should be promoted to evaluate the natural course of negative symptoms, improve our ability to identify the different sources of secondary negative symptoms, provide effective interventions, and target primary and persistent negative symptoms with innovative treatment strategies. Further research is needed to identify pathophysiological mechanisms of primary negative symptoms and foster the development of new treatments.

Switching Antipsychotic Medications in People with Schizophrenia: A 4-Year Naturalistic Study.

Although generally effective in ameliorating the core manifestations of schizophrenia, antipsychotics (APs) may lead to only suboptimal responses or may be associated with a variety of treatment-related adverse events which require additional treatment strategies. Under such clinical circumstances, switching APs represents a rational treatment option. The present study aimed to identify the variables that predict AP switch and to quantify the frequency of this phenomenon in people with schizophrenia in real-life. A secondary analysis was conducted on the data collected at baseline and at a 4-year follow-up from a large sample of community-dwelling Italian people with schizophrenia. Demographic and clinical variables as well as information about AP treatment were recorded at two time points. Over the 4-year period, 34.9% of the 571 participants switched the AP; in particular, 8.4% of participants switched from first-generation APs (FGAs) to second-generation APs or vice versa, while 8.2% of them switched to clozapine. Logistic regression models showed that combination of APs at baseline was negatively associated with AP switch, while treatment with FGAs and the presence of extrapyramidal symptoms at baseline were associated with AP class switch. Although the aim of the present study was not to assess predictors of clinical relapse in people with schizophrenia, we might speculate that switching APs represents a surrogate indicator of treatment failure in some patients and could lead into relapse, which is a costly aspect of schizophrenia management in both economic and human terms. The sooner such a negative outcome can be predicted and managed, the sooner the treatment can be optimized to avoid it.

Unveiling the Associations between EEG Indices and Cognitive Deficits in Schizophrenia-Spectrum Disorders: A Systematic Review.

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.

Searching for bridges between psychopathology and real-world functioning in first-episode psychosis: A network analysis from the OPTiMiSE trial.

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.

European Psychiatric Association guidance on treatment of cognitive impairment in schizophrenia.

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.