In people suffering from schizophrenia, major areas of everyday life are impaired, including independent living, productive activities and social relationships. Enhanced understanding of factors that hinder real-life functioning is vital for treatments to translate into more positive outcomes. The goal of the present study was to identify predictors of real-life functioning in people with schizophrenia, and to assess their relative contribution. Based on previous literature and clinical experience, several factors were selected and grouped into three categories: illness-related variables, personal resources and context-related factors. Some of these variables were never investigated before in relationship with real-life functioning. In 921 patients with schizophrenia living in the community, we found that variables relevant to the disease, personal resources and social context explain 53.8% of real-life functioning variance in a structural equation model. Neurocognition exhibited the strongest, though indirect, association with real-life functioning. Positive symptoms and disorganization, as well as avolition, proved to have significant direct and indirect effects, while depression had no significant association and poor emotional expression was only indirectly and weakly related to real-life functioning. Availability of a disability pension and access to social and family incentives also showed a significant direct association with functioning. Social cognition, functional capacity, resilience, internalized stigma and engagement with mental health services served as mediators. The observed complex associations among investigated predictors, mediators and real-life functioning strongly suggest that integrated and personalized programs should be provided as standard treatment to people with schizophrenia.

Improving real‐life functioning is the main goal of the most advanced integrated treatment programs in people with schizophrenia. The Italian Network for Research on Psychoses previously explored, by using network analysis, the interplay among illness‐related variables, personal resources, context‐related factors and real‐life functioning in a large sample of patients with schizophrenia. The same research network has now completed a 4‐year follow‐up of the original sample. In the present study, we used network analysis to test whether the pattern of relationships among all variables investigated at baseline was similar at follow‐up. In addition, we compared the network structure of patients who were classified as recovered at follow‐up versus those who did not recover. Six hundred eighteen subjects recruited at baseline could be assessed in the follow‐up study. The network structure did not change significantly from baseline to follow‐up, and the overall strength of the connections among variables increased slightly, but not significantly. Functional capacity and everyday life skills had a high betweenness and closeness in the network at follow‐up, as they had at baseline, while psychopathological variables remained more peripheral. The network structure and connectivity of non‐recovered patients were similar to those observed in the whole sample, but very different from those in recovered subjects, in which we found few connections only. These data strongly suggest that tightly coupled symptoms/dysfunctions tend to maintain each other's activation, contributing to poor outcome in schizophrenia. Early and integrated treatment plans, targeting variables with high centrality, might prevent the emergence of self‐reinforcing networks of symptoms and dysfunctions in people with schizophrenia.

IMPORTANCEThe goal of schizophrenia treatment has shifted from symptom reduction and relapse prevention to functional recovery; however, recovery rates remain low. Prospective identification of variables associated with real-life functioning domains is essential for personalized and integrated treatment programs. OBJECTIVE To assess whether baseline illness-related variables, personal resources, and context-related factors are associated with work skills, interpersonal relationships, and everyday life skills at 4-year follow-up. DESIGN, SETTING, AND PARTICIPANTSThis multicenter prospective cohort study was conducted across 24 Italian university psychiatric clinics or mental health departments in which 921 patients enrolled in a cross-sectional study were contacted after 4 years for reassessment. Recruitment of community-dwelling, clinically stable persons with schizophrenia was conducted from March 2016 to December 2017, and data were analyzed from January to May 2020.MAIN OUTCOMES AND MEASURES Psychopathology, social and nonsocial cognition, functional capacity, personal resources, and context-related factors were assessed, with real-life functioning as the main outcome. Structural equation modeling, multiple regression analyses, and latent change score modeling were used to identify variables that were associated with real-life functioning domains at follow-up and with changes from baseline in these domains. RESULTSIn total, 618 participants (427 male [69.1%]; mean [SD] age, 45.1 [10.5] years) were included. Five baseline variables were directly associated with real-life functioning at follow-up: neurocognition with everyday life (β, 0.274; 95% CI, 0.207-0.341; P < .001) and work (β, 0.101; 95% CI, 0.005-0.196; P = .04) skills; avolition with interpersonal relationships (β, −0.126; 95% CI, −0.190 to −0.062; P < .001); positive symptoms with work skills (β, −0.059; 95% CI, −0.112 to −0.006; P = .03); and social cognition with work skills (β, 0.185; 95% CI, 0.088-0.283; P < .001) and interpersonal functioning (β, 0.194; 95% CI, 0.121-0.268; P < .001). Multiple regression analyses indicated that these variables accounted for the variability of functioning at follow-up after controlling for baseline functioning. In the latent change score model, higher neurocognitive abilities were associated with improvement of everyday life (β, 0.

Background. Greater levels of insight may be linked with depressive symptoms among patients with schizophrenia, however, it would be useful to characterize this association at symptom-level, in order to inform research on interventions. Methods. Data on depressive symptoms (Calgary Depression Scale for Schizophrenia) and insight (G12 item from the Positive and Negative Syndrome Scale) were obtained from 921 community-dwelling, clinically-stable individuals with a DSM-IV diagnosis of schizophrenia, recruited in a nationwide multicenter study. Network analysis was used to explore the most relevant connections between insight and depressive symptoms, including potential confounders in the model (neurocognitive and social-cognitive functioning, positive, negative and disorganization symptoms, extrapyramidal symptoms, hostility, internalized stigma, and perceived discrimination). Bayesian network analysis was used to estimate a directed acyclic graph (DAG) while investigating the most likely direction of the putative causal association between insight and depression. Results. After adjusting for confounders, better levels of insight were associated with greater self-depreciation, pathological guilt, morning depression and suicidal ideation. No difference in global network structure was detected for socioeconomic status, service engagement or illness severity. The DAG confirmed the presence of an association between greater insight and self-depreciation, suggesting the more probable causal direction was from insight to depressive symptoms. Conclusions. In schizophrenia, better levels of insight may cause self-depreciation and, possibly, other depressive symptoms. Person-centered and narrative psychotherapeutic approaches may be particularly fit to improve patient insight without dampening self-esteem.

Given the absence of high quality evidence and the inability to draw firm conclusions based on that evidence, the use of SAMe for the treatment of depression in adults should be investigated further. Future trials should be in the form of large randomised controlled clinical trials of high methodological quality, with particular attention given to randomisation, allocation concealment, blinding and the handling of missing data. Comparator antidepressants from all classes should be used. Adverse events should be detailed for each participant, bearing in mind that induction of mania is of particular interest.