Impact of Physical Exercise Alone or in Combination with Cognitive Remediation on Cognitive Functions in People with Schizophrenia: A Qualitative Critical Review

: Physical exercise and cognitive remediation represent the psychosocial interventions with the largest basis of evidence attesting their effectiveness in improving cognitive performance in people living with schizophrenia according to recent international guidance. The aims of this review are to provide an overview of the literature on physical exercise as a treatment for cognitive impairment in schizophrenia and of the studies that have combined physical exercise and cognitive remediation as an integrated rehabilitation intervention. Nine meta-analyses and systematic reviews on physical exercise alone and seven studies on interventions combining physical exercise and cognitive remediation are discussed. The efficacy of physical exercise in improving cognitive performance in people living with schizophrenia is well documented, but more research focused on identifying moderators of participants response and optimal modalities of delivery is required. Studies investigating the effectiveness of integrated interventions report that combining physical exercise and cognitive remediation provides superior benefits and quicker improvements compared to cognitive remediation alone, but most studies included small samples and did not explore long-term effects. While physical exercise and its combination with cognitive remediation appear to represent effective treatments for cognitive impairment in people living with schizophrenia, more evidence is currently needed to better understand how to implement these treatments in psychiatric rehabilitation practice

The Elephant in the Room: A Cross-Sectional Study on the Stressful Psychological Effects of the COVID-19 Pandemic in Mental Healthcare Workers

Despite extensive research on COVID-19’s impact on healthcare workers, few studies have targeted mental health workers (MHWs) and none have investigated previous traumatic events. We investigated psychological distress in MHWs after the first lockdown in Italy to understand which COVID-19, sociodemographic, and professional variables represented greater effects, and the role of previous trauma. The survey included sociodemographic and professional questions, COVID-19 variables, and the questionnaires Life Events Checklist for DSM-5 (LEC-5), Impact of Event Scale—Revised (IES-R), and Depression Anxiety Stress Scales 21 (DASS-21). On the 271 MHWs who completed the survey (73.1% female; mean age 45.37), we obtained significant effects for contagion fear, experience of patients’ death, increased workload, and worse team relationship during the first wave. Nurses were more affected and showed more post-traumatic stress symptoms, assessed by IES-R, and more depressive, anxiety, and stress symptoms, assessed by DASS-21. The strongest risk factors for distress were greater age, professional role, increased workload, worse team relationship, and separation from family members. Previous experience of severe human suffering and unwanted sexual experiences negatively impacted IES-R and DASS-21 scores. Being a psychiatrist or psychologist/psychotherapist and good team relationships were protective factors. Recent but also previous severe stressful events might represent relevant risk factors for distress, reducing resilience skills. Identifying vulnerable factors and professional categories may help in the development of dedicated measures to prevent emotional burden and support psychological health. Highlights: Psychological distress in mental health workers in the COVID-19 pandemic is more frequent in nurses, who experience more depression, anxiety, and post-traumatic stress symptoms. Previous and recent stressful events are risk factors for distress and should guide intervention strategies

Factors Associated With Response and Resistance to Cognitive Remediation in Schizophrenia: A Critical Review

Cognitive impairment is a central feature of schizophrenia and has shown to play a crucial role in the psychosocial function of the disorder. Over the past few years, several cognitive remediation (CR) interventions have been developed for schizophrenia, whose effectiveness has also been widely demonstrated by systematic reviews and meta-analysis studies. Despite these evidences, many questions remain open. In particular, the identification of CR response predictors in patients with schizophrenia is still a topic with equivocal findings and only a few studies have looked for the relationship between CR response or resistance and the biological, socio-demographic, clinical and cognitive features in schizophrenia. The current knowledge on positive or negative response predictors to CR treatment in schizophrenia include: age, duration of illness, premorbid adjustment, baseline cognitive performance, intrinsic motivation, hostility, disorganized symptoms, neurobiological reserve, genetic polymorphisms, the amounts of antipsychotics, the type of CR, etc. The aim of this review is to identify neurobiological, psychopathological, cognitive, and functional predictors of CR response or resistance in schizophrenia, taking into account both cognitive and functional outcome measures. The information obtained could be very useful in planning integrated and personalized interventions, also with a better use of the available resources

Treatment-Resistant Schizophrenia: Genetic and Neuroimaging Correlates

Schizophrenia is a severe neuropsychiatric disorder that affects approximately 0.5–1% of the population. Response to antipsychotic therapy is highly variable, and it is not currently possible to predict those patients who will or will not respond to antipsychotic medication. Furthermore, a high percentage of patients, approximately 30%, are classified as treatment-resistant (treatment-resistant schizophrenia; TRS). TRS is defined as a non-response to at least two trials of antipsychotic medication of adequate dose and duration. These patients are usually treated with clozapine, the only evidence-based pharmacotherapy for TRS. However, clozapine is associated with severe adverse events. For these reasons, there is an increasing interest to identify better targets for drug development of new compounds and to establish better biomarkers for existing medications. The ability of antipsychotics to improve psychotic symptoms is dependent on their antagonist and reverse agonist activities at different neuroreceptors, and some genetic association studies of TRS have focused on different pharmacodynamic factors. Some genetic studies have shown an association between antipsychotic response or TRS and neurodevelopment candidate genes, antipsychotic mechanisms of action (such as dopaminergic, serotonergic, GABAergic, and glutamatergic) or pharmacokinetic factors (i.e., differences in the cytochrome families). Moreover, there is a growing body of literature on the structural and functional neuroimaging research into TRS. Neuroimaging studies can help to uncover the underlying neurobiological reasons for such resistance and identify resistant patients earlier. Studies examining the neuropharmacological mechanisms of antipsychotics, including clozapine, can help to improve our knowledge of their action on the central nervous system, with further implications for the discovery of biomarkers and the development of new treatments. The identification of the underlying mechanisms of TRS is a major challenge for developing personalized medicine in the psychiatric field for schizophrenia treatment. The main goal of precision medicine is to use genetic and brain-imaging information to improve the safety, effectiveness, and health outcomes of patients via more efficiently targeted risk stratification, prevention, and tailored medication and treatment management approaches. The aim of this review is to summarize the state of art of pharmacogenetic, pharmacogenomic and neuroimaging studies in TRS

Autistic symptoms in unaffected first-degree relatives of people with schizophrenia: results from the Italian Network for Research on Psychoses multicenter study

Background. Autistic symptoms represent a frequent feature in schizophrenia spectrum disorders (SSD). However, the prevalence and the cognitive and functional correlates of autistic symptoms in unaffected first-degree relatives of people with SSD remain to be assessed.Methods. A total of 342 unaffected first-degree relatives related to 247 outpatients with schizophrenia were recruited as part of the multicenter study of the Italian Network for Research on Psychoses (NIRP). Autistic features were measured with the PANSS Autism Severity Scale. Three groups of participants, defined on the presence and severity of autistic symptoms, were compared on a wide array of cognitive and functional measures.Results. Of the total sample, 44.9% presented autistic symptoms; 22.8% showed moderate levels of autistic symptoms, which can be observed in the majority of people with SSD. Participants with higher levels of autistic symptoms showed worse performance on Working Memory (p = 0.014) and Social Cognition (p = 0.025) domains and in the Global Cognition composite score (p = 0.008), as well as worse on functional capacity (p = 0.001), global psychosocial functioning (p < 0.001), real-world interpersonal relationships (p < 0.001), participation in community activities (p = 0.017), and work skills (p = 0.006).Conclusions. A high prevalence of autistic symptoms was observed in first-degree relatives of people with SSD. Autistic symptoms severity showed a negative correlation with cognitive performance and functional outcomes also in this population and may represent a diagnostic and treatment target of considerable scientific and clinical interest in both patients and their first-degree relatives

The influence of autistic symptoms on social and non-social cognition and on real-life functioning in people with schizophrenia: Evidence from the Italian Network for Research on Psychoses multicenter study

BACKGROUND: Autism spectrum disorders (ASDs) and schizophrenia spectrum disorders (SSDs), although conceptualized as separate entities, may share some clinical and neurobiological features. ASD symptoms may have a relevant role in determining a more severe clinical presentation of schizophrenic disorder but their relationships with cognitive aspects and functional outcomes of the disease remain to be addressed in large samples of individuals. AIMS: To investigate the clinical, cognitive, and functional correlates of ASD symptoms in a large sample of people diagnosed with schizophrenia. METHODS: The severity of ASD symptoms was measured with the PANSS Autism Severity Scale (PAUSS) in 921 individuals recruited for the Italian Network for Research on Psychoses multicenter study. Based on the PAUSS scores, three groups of subjects were compared on a wide array of cognitive and functional measures. RESULTS: Subjects with more severe ASD symptoms showed a poorer performance in the processing speed (p\ua0=\ua00.010), attention (p\ua0=\ua00.011), verbal memory (p\ua0=\ua00.035), and social cognition (p\ua0=\ua00.001) domains, and an overall lower global cognitive composite score (p\ua0=\ua00.010). Subjects with more severe ASD symptoms also showed poorer functional capacity (p\ua0=\ua00.004), real-world interpersonal relationships (p\ua0<\ua00.001), and participation in community-living activities (p\ua0<\ua00.001). CONCLUSIONS: These findings strengthen the notion that ASD symptoms may have a relevant impact on different aspects of the disease, crucial to the life of people with schizophrenia. Prominent ASD symptoms may characterize a specific subpopulation of individuals with SSD

The mediating effect of mood spectrum on the relationship between autistic traits and catatonia spectrum

BackgroundIn the recent years, several studies have shown a correlation between autism spectrum disorder (ASD) and catatonia. It is also known that both conditions are found to be associated with mood disorders. This study aimed to investigate the relationship between autistic traits and catatonic symptoms, as well as the potential mediating role of mood disorder spectrum in the relationship between them.MethodsThe total sample of 514 subjects was composed by four diagnostic groups, composed by patients affected by catatonia (CTN), borderline personality disorder (BPD), major depressive disorder (MDD) and healthy controls (HC). Subjects were assessed with the SCID-5-RV, the Adult Autism Subthreshold Spectrum (AdAS Spectrum) and the Catatonia Spectrum (CS) and the Mood Spectrum Self-Report (MOODS-SR). Statistical analyses included Pearson’s coefficient calculation, multiple linear regression, and mediation analysis.Resultsall the correlations appear to be strongly positive and significant with the strongest coefficient emerging between AdAS Spectrum total score and CS total score (r = 0.762, p &lt; 0.001). The Mediation Analysis showed that AdAS Spectrum total score showed a significant indirect effect on CS total score through MOODS-SR total score (b = 0.168, 95% bootstrapped CI [0.127:0.207]).ConclusionThe present study highlights the presence of a mediating role of the mood disorder spectrum in the relationship between autistic traits and the catatonia spectrum

Insight in cognitive impairment assessed with the Cognitive Assessment Interview in a large sample of patients with schizophrenia

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

The interplay among psychopathology, personal resources, context-related factors and real-life functioning in schizophrenia: stability in relationships after 4 years and differences in network structure between recovered and non-recovered patients

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