Schizophrenia, bipolar depression and major depressive disorders collectively affect over 10 million people across the European Union and are associated with annual healthcare and societal costs of more than 600 billion euros. When diagnosed, patients are usually prescribed psychotropic medication. A substantial proportion of patients insufficiently responds to first- and second-line treatments, which is termed as treatment resistance. While third-line treatments are relatively effective in TR conditions, it remains unclear whether providing these treatments in an earlier phase provides benefits. INTENSIFY consists of three international, multicenter, controlled, randomized, open-label trials, with a treatment duration of 6 weeks. After failure of a first-line treatment in the current episode, 1254 participants will be recruited by at least 16 sites and randomized to either a third-line treatment (early intensified pharmacological treatment) or treatment as usual (standard second-line treatment). Adult participants (age ≥ 18yrs) with a diagnosis of schizophrenia, schizoaffective disorder or schizophreniform disorder, major depressive disorder, or bipolar depression are eligible after a treatment failure in the current episode due to lack of efficacy. The primary objective is to compare change in symptom severity after 6 weeks. The secondary objective is to compare the two treatment arms on changes of severity symptoms, cognitive function, quality of life, functional measures, digital mental health markers, side effects and concomitant medication. ANCOVA analyses will be performed. Should the current study show clinical evidence that the use of third-line treatment is efficacious and safe earlier to treat severe mental illness, the results could impact treatment guidelines in due course. In addition, the study will contribute to the identification of clinical, digital and blood-based markers that are associated with treatment response to early and intensified treatments. The trials are registered in www.clinicaltrials.gov under numbers NCT05603104 (merged study protocol; study center in Israel) and under the numbers for the split protocols NCT05958875 (SZ), NCT05973786 (BD) and NCT05973851 (MDD) for the EU and UK sites. The study is registered in the Australian and New Zealand Clinical Trials Registry under Registration number ACTRN12625000327482 (SZ), ACTRN12625000328471 (BD) and ACTRN12625000329460 (MDD). Registered on April 17, 2025.

Introduction Negative symptoms are a core feature of schizophrenia and severely impact functioning and quality of life. The five symptom domains (anhedonia, asociality, avolition, blunted affect, and alogia) have emerged as the preferred structure of negative symptoms; however, it is unclear whether these dimensions demonstrate measurement bias across sociodemographic variables. We used regularized moderated nonlinear factor analysis (MNLFA) to evaluate potential sociodemographic bias in the measurement of negative symptoms among individuals with schizophrenia. Methods The study included two samples of people with schizophrenia (total n = 1175). Negative symptoms were assessed with the Brief Negative Symptom Scale. Regularized MNLFA was conducted to assess whether the five-factors of negative symptoms showed measurement bias at the item and latent levels as a function of age, education level, and sex. Results At the item level, the asociality behavior item showed differential item functioning, such that older participants were more likely to endorse more severe deficits on this item after accounting for their latent level of asociality. In addition, those with higher education levels were more likely to endorse more severe deficits on the avolition internal experience item after accounting for their latent level of avolition. Measurement bias was also present across all five of the latent negative symptom variables. Conclusion As negative symptoms increasingly serve as treatment targets and surrogate outcomes, ensuring unbiased measurement is essential for advancing clinical precision. The presence of measurement bias underscores the need for careful consideration of age, education, and sex when interpreting symptom scores in both research and clinical settings.

Abstract Persistent negative symptoms (PNS), defined as negative symptoms of at least moderate severity that endure over time and are not attributable to other psychopathological dimensions such as depression or parkinsonism, have been associated with poor functional outcomes in schizophrenia, in both chronic stages and in the early phases of the disorder. This post-hoc analysis of a large cohort of schizophrenia spectrum disorder patients within their first 7 years of illness, enrolled in the European Long-acting Antipsychotics in Schizophrenia Trial (EULAST), aimed to: 1) confirm prior findings about the prevalence and clinical impact of unconfounded persistent negative symptoms (PNS) on dropout rates and psychosocial functioning after 12 and 18 months of treatment; and 2) explore the prevalence of enduring negative symptoms (E-NS), defined as persistent negative symptoms either confounded or unconfounded by depression or parkinsonism, and their influence on functional outcome. At week 0, 60.6% of patients exhibited at least one negative symptom of moderate severity. Among them, 42.8% met criteria for unconfounded negative symptoms. After 1 year, the frequency of PNS and E-NS was 7.9% and 15%, respectively, with a prospective consistency around 32%. PNS subjects had similar levels of functioning at week 0 (d = −0.179, p = 0.194), but worse functioning after 12 (d = −0.697, p = 0.028) and 18 (d = -0.676, p = 0.024) months of treatment, as compared to those with negative symptoms of similar severity at baseline that did not persist (non-persistent negative symptoms, N-PNS). No difference among groups was observed in drop-out rates. The comparison between the E-NS and N-PNS groups revealed the same functional outcome differences observed in the PNS versus N-PNS comparison. Our findings confirm that long-term persistence of negative symptoms, both primary and secondary, contributes to poor functional outcome. Future research should focus on identifying predictors of symptom persistence to guide the development of targeted interventions aimed at improving long-term functional outcomes in this patient population.

IntroductionEvent-related potentials (ERPs), recorded through electroencephalography (EEG) during sensory and cognitive tasks, have been consistently employed to investigate electrophysiological correlates of psychiatric disorders. However, traditional peak component analysis of ERPs is limited by the a priori selection of time windows and electrodes. Microstate analysis, a data-driven approach based on identifying periods of quasi-stable scalp topographies, has been applied to ERP data, offering a valuable tool for understanding the temporal dynamics of large-scale neural networks. This review aims to provide a comprehensive summary of studies examining event-related microstates in individuals with psychiatric disorders.MethodsA systematic review of English-language articles indexed in PubMed, Scopus, and Web of Science (WoS) was conducted on May 1, 2024. Studies were included only if they applied microstate analysis to ERP data and analyzed data from at least one group of patients with psychiatric disorders in comparison to healthy controls.ResultsOf the 1,115 records screened, 17 studies were included in the final qualitative synthesis. The majority of these studies (n=8) included patients with schizophrenia, using various tasks focusing mainly on visuospatial processing (n=6) and face processing (n=6). Regarding the microstate methodology, the primary clustering approach employed was the k-means clustering algorithm (n=8), while the cross-validation criterion (n=10) was the most commonly used measure of fit. Sixteen of the 17 studies reported at least one significant difference in microstate features between patients and healthy controls, mainly in the temporal and topographic characteristics of microstates and the sequence of their occurrence.ConclusionsThis review highlights the value of event-related potential microstates analysis in identifying spatiotemporal alterations in brain dynamics associated with psychiatric disorders. However, the limited number of studies and the heterogeneity of experimental paradigms constrain the generalizability of the findings.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42024529185.

INTRODUCTION:Negative symptoms, such as apathy and diminished motivation, are critical for prognosis and treatment outcomes in neurological and psychiatric disorders. However, constructs and assessment scales differ significantly across neuropsychiatric disorders. This study examines the psychometric properties of two scales used to assess apathy - the apathy-motivation index (AMI) and the diagnostic criteria for apathy (DCA) - compared to schizophrenia-specific tools, namely the brief negative symptoms scale (BNSS) and the positive and negative syndrome scale (PANSS). METHODS:We conducted a cross-sectional, multicenter study with 151 individuals with schizophrenia across six European sites. Participants were assessed using the AMI, DCA, BNSS, PANSS, and other clinical and functional scales. BNSS motivation and pleasure factor (BNSS_MAP) assessed motivation, and personal and social performance (PSP) assessed functioning. Convergent validity across these tools was examined through bivariate correlations (Pearson r) and exploratory factor analysis for the AMI. Cut-off points for apathy used receiver operating characteristic (ROC) analysis, with DCA as the reference. RESULTS:We found low convergence between BNSS_MAP and AMI (r=.31, p<.001) and moderate convergence between BNSS_MAP and DCA (r=.48, p<.001). PSP correlated with BNSS_MAP, PANSS_negative and DCA (r=-.615, r=-.446 and r=-.430, respectively, all p<0.001), but not with AMI (r=-.108; p=.218). ROC analysis yielded cut-off points of 28.5 (BNSS total), 16.5 (BNSS_MAP), 14.5 (PANSS_negative), and 33.5 (AMI total) for detecting clinical apathy. CONCLUSION:Current apathy and motivation scales show limited overlap, reflecting the complexity of measuring transdiagnostic constructs. Combining clinician- and patient-rated measures may provide a more comprehensive understanding of apathy in schizophrenia and other neuropsychiatric conditions.

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.

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.

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.

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.

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.

BACKGROUND:The 22q11.2 deletion syndrome (22q11.2DS) entails intellectual disabilities and higher risk of psychotic disorders. Neurocognitive deficits predict real-life functioning of schizophrenic patients. We investigated real-life functioning in 22q11.2DS, aiming at defining how neurocognitive profile and psychopathological variables impact on psychotic patients' social functioning. METHODS:We recruited 63 patients with schizophrenia (SCZ, N = 63), 44 with 22q11.2DS (DEL, N = 44) and 19 with 22q11.2DS and psychosis (DEL-SCZ, N = 19), all matched for age, sex and neurocognitive profile; we administered the Positive and Negative Syndrome Scale (PANSS), the Brief Negative Symptom Scale (BNSS), the Specific Levels of Functioning (SLoF) scale and the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB). We implemented descriptive analyses, MANCOVA and linear regression statistics. RESULTS:The DEL-SCZ and the SCZ groups showed similar levels in Interpersonal Relationships (p = 0.093) and Social Acceptability subscales (p = 0.283). The DEL group scored higher on the Interpersonal Relationships subscale compared with the SCZ group (p = 0.001). The groups scored similarly on the other SLoF subscales. Both BNSS total score (beta = -0.343; p = 0.004) and BNSS asociality (beta = -0.487; p = 0.038) significantly predicted the Interpersonal Relationships variable in the groups with psychosis (SCZ and DEL-SCZ). DISCUSSION AND CONCLUSIONS:Individuals with 22q11.2DS display a similar real-life functioning to patients with chronic schizophrenia. Social functioning impairments are typical of psychosis regardless of the genetic condition and highly predicted by negative symptoms like asociality. The 22q11.2DS represents a reliable biological model to study vulnerability to psychosis and its consequences on patients' real-life and social functioning.

BACKGROUND:Although obsessive-compulsive disorder (OCD) is highly prevalent in schizophrenia, its relationship with patients' real-life functioning is still controversial.METHODS:The present study aims at investigating the prevalence of OCD in a large cohort of non-preselected schizophrenia patients living in the community and verifying the relationship of OCD, as well as of other psychopathological symptoms, with real-life functioning along a continuum of OCD severity and after controlling for demographic variables.RESULTS:A sample of 327 outpatients with schizophrenia was enrolled in the study and collapsed into three subgroups according to OCD severity (subclinical, mild-moderate, severe). A series of structural equation modeling (SEM) was performed to analyze in each subgroup the association of obsessive-compulsive symptoms with real-life functioning, assessed through the Specific Levels of Functioning Scale and the UCSD Performance-Based Skills Assessment. Moreover, latent profile analysis (LPA) was performed to infer latent subpopulations. In the subclinical OCD group, obsessive-compulsive symptoms (OCS) were not associated with functioning, whereas in the mild-moderate OCD group, they showed a positive relationship, particularly in the domains of work and everyday life skills. The paucity of patients with severe OCD did not allow performing SEM analysis in this group. Finally, LPA confirmed a subgroup with mild-moderate OCS and more preserved levels of functioning.CONCLUSIONS:These findings hint at a positive association between mild-moderate OCD and real-life functioning in individuals with schizophrenia and encourage a careful assessment of OCD in personalized programs to sustain daily life activities.

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.

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.

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.

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.

Background: Mental disorders that are comorbid with chronic infectious diseases may worsen clinical outcomes and patients’ quality of life. We hypothesized that depression and/or anxiety syndromes or symptoms comorbid with human immunodeficiency virus (HIV) or hepatitis B virus (HBV) infection might stem from shared biological mechanisms. Methods: We conducted a systematic review applying the PRISMA statement by searching into the PubMed, APA PsycInfo, and Scopus databases. We examined the literature on HIV/HBV infection comorbid with depression and/or anxiety in adults ≥18 years. Results: Thirty-one studies on HIV and three on HBV were analyzed. The Tat protein contributed to HIV-associated mood disorders due to the protein’s ability to cause neurodegeneration and induce hypothalamic–pituitary–adrenal (HPA) axis dysregulation in response to natural stressors. The decreased brain-derived neurotrophic factor (BDNF) levels also emerged as a mechanism involved in HIV neuropathogenesis and the associated mood symptoms. Neuroinflammation was implicated in depression and/or anxiety onset in patients with HIV/HBV infections. Microglial activation and release of cytokines, in particular, appeared as potential pathogenetic mechanisms. Furthermore, an altered balance between quinolinic acid and kynurenic acid production emerged in HIV patients with comorbid depression, indicating a glutamatergic dysfunction. Inflammatory cytokine production and the downregulation of cellular immune responses contributed to persisting inflammation, delayed healing, and functional decline in patients with chronic hepatitis B (CHB) infection. A shift in type 1–type 2 cytokine balance might be implicated in HBV-related immune pathogenesis, and depression and anxiety might be considered immunomodulatory factors. Cytokines also caused HPA axis hyperactivity, frequently observed in HIV/HBV patients with comorbid depression/anxiety. Conclusions: The present systematic review showed, for the first time, that HIV/HBV and depression and/or anxiety might have several biological mechanisms as common denominators. The longitudinal course of the highlighted biological mechanisms should be explored to establish the causative interrelationship among the involved mechanisms. In addition, future research should investigate the possibility that a patient’s clinical outcome might improve using pharmacological treatments acting on the biological mechanisms we described as common denominators of chronic inflammatory infective diseases and depression/anxiety.

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.

BackgroundThe 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.MethodsClinical 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.ResultsThe 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.ConclusionsOur 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.

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.