Durability of Effects of Cognitive Remediation on Cognition and Psychosocial Functioning in Schizophrenia: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

OBJECTIVE: Cognitive remediation provides substantial improvements in cognitive performance and real-world functioning for people living with schizophrenia, but the durability of these benefits needs to be reassessed and better defined. The aims of this study were to provide a comprehensive assessment of the durability of the benefits of cognitive remediation for cognition and functioning in people living with schizophrenia and evaluating potential moderators of effects. METHODS: A systematic search was conducted in PubMed, Scopus, and PsycINFO, and reference lists of included articles and Google Scholar were inspected. Eligible studies were randomized clinical trials of cognitive remediation in patients diagnosed with schizophrenia spectrum disorders in which follow-up assessments were included. Screening and data extraction were performed by at least two independent reviewers. Cohen's d was used to measure outcomes. Primary outcomes were changes in cognition and functioning from baseline to conclusion of follow-up. Moderators of the durability of effects were assessed. RESULTS: Of 2,840 identified reports, 281 full texts were assessed and 130 reports on 67 studies with 5,334 participants were included. Cognitive remediation produced statistically significant positive effects that persisted at the end of follow-up in global cognition (d=0.23) and in global functioning (d=0.26). Smaller study samples and single-center studies were associated with better cognitive outcomes; longer treatment and follow-up duration, techniques for transferring cognitive gains to the real world, integration with psychiatric rehabilitation, group format of delivery, and more female participants in the sample were associated with better functional outcomes. CONCLUSIONS: Cognitive remediation provides durable improvements in cognition and functioning in schizophrenia. This finding corroborates the notion that cognitive remediation should be implemented more widely in clinical and rehabilitation practice.

Evidence-based psychosocial interventions in schizophrenia: a critical review.

PURPOSE OF REVIEW: Schizophrenia Spectrum Disorders (SSD) are severe conditions that frequently produce significant impairment in cognitive performance, social skills and psychosocial functioning. As pharmacological treatment alone often provides only limited improvements on these outcomes, several psychosocial interventions are employed in psychiatric rehabilitation practice to improve of real-world outcomes of people living with SSD: the present review aims to provide a critical overview of these treatments, focusing on those that show consistent evidence of effectiveness. RECENT FINDINGS: Several recent systematic reviews and meta-analyses have investigated in detail the acceptability, the effectiveness on several specific outcomes and moderators of response of different psychosocial interventions, and several individual studies have provided novel insight on their implementation and combination in rehabilitation practice. SUMMARY: Cognitive remediation, metacognitive training, social skills training, psychoeducation, family interventions, cognitive behavioral therapy, physical exercise and lifestyle interventions, supported employment and some other interventions can be fully considered as evidence-based treatments in SSD. Psychosocial interventions could be of particular usefulness in the context of early intervention services. Future research should focus on developing newer interventions, on better understanding the barriers and the facilitators of their implementation in clinical practice, and exploring the opportunities provided by novel technologies.

What impact can brain stimulation interventions have on borderline personality disorder?

INTRODUCTION: Borderline personality disorder (BPD) is a severe mental disorder characterized by emotion dysregulation, impulsivity, neuropsychological impairment, and interpersonal instability, presenting with multiple psychiatric comorbidities, functional disability and reduced life expectancy due suicidal behaviors. AREAS COVERED: In this perspective, the authors explore the application of noninvasive brain stimulation (NIBS) (rTMS, tDCS, and MST) in BPD individuals by considering a symptom-based approach, focusing on general BPD psychopathology, impulsivity and neuropsychological impairments, suicidality and depressive/anxious symptoms, and emotion dysregulation. EXPERT OPINION: According to a symptoms-based approach, NIBS interventions (particularly rTMS and tDCS) are promising treatment options for BPD individuals improving core symptoms such as emotional and behavioral dysregulation, neuropsychological impairments and depressive symptoms. However, the heterogeneity of stimulation protocols and of assessment tools used to detect these changes limits the possibility to provide definitive recommendations according to a symptom-based approach. To implement such armamentarium in clinical practice, future NIIBS studies should further consider a lifespan perspective due to clinical variability over time, the role of psychiatric comorbidities affecting BPD individuals and the need to combine NIBS with specialized psychotherapeutic approaches for BPD patients and with functional neuroimaging studies.

Application of cognitive remediation in the world: new experiences from two schizophrenia rehabilitation centers in Togo and Benin.

PURPOSE: People with schizophrenia in Sub-Saharan Africa often live in very difficult conditions, suffer important social isolation and usually do not receive any kind of treatment. In this context, some non-governmental initiatives have come to light, providing accommodation, food, primary healthcare, medications and, in some cases, education and rehabilitation. The aims of this study were to assess feasibility, effects, and acceptability of a Cognitive Remediation Therapy (CRT) intervention in the particular context of psychiatric rehabilitation in Togo and Benin. METHODS: Patients diagnosed with schizophrenia accessing the "Saint Camille" association rehabilitation centers in Togo and Benin during the enrollment period were allocated consecutively with a 1:1 proportion to receive a manualized CRT intervention (46 one-hour sessions over 14 weeks) or continuing Treatment As Usual (TAU). The assessment included validated measures of cognitive performance and real-world functioning and was performed at baseline and at the conclusion of treatment. RESULTS: All subjects that were invited into the study agreed to participate and completed the intervention, for a total of 36 participants. CRT produced greater improvements than TAU in processing speed, working memory, verbal memory, cognitive flexibility, and executive functions measures, with moderate to large effect sizes, in particular in processing speed and working memory domains. CONCLUSIONS: CRT represents a feasible and effective psychosocial intervention that can be implemented even in contexts with very limited resources, and could represent an important instrument to promote the rehabilitation process of people living with schizophrenia in low-income countries.

Improving depressive symptoms in patients with schizophrenia using bilateral bipolar-nonbalanced prefrontal tDCS: Results from a double-blind sham-controlled trial.

BACKGROUND: Treating depressive symptoms in patients with schizophrenia is challenging. While transcranical Dicrect Current Stimulation (tDCS) improved other core symptoms of schizophrenia, conflicting results have been obtained on depressive symptoms. Thus, we aimed to expand current evidence on tDCS efficacy to improve depressive symptoms in patients with schizophrenia. METHODS: A double-blind RCT was performed with patients randomized to 2 mA active-tDCS or sham-tDCS (15 daily sessions) with a bilateral bipolar-nonbalanced prefrontal placement (anode: left Dorsolateral prefrontal cortex; cathode: right orbitofrontal region). Clinical outcomes included variations of Calgary Depression Scale for Schizophrenia total score (CDSS) and of Depression-hopelessness and Guilty idea of reference-pathological guilt factors. Analysis of covariance was performed evaluating between-group changes over time. The presence/absence of probable clinically significant depression was determined when CDSS > 6. RESULTS: As 50 outpatients were included (both groups, n = 25), significant improvements following active-tDCS were observed for CDSS total score (p = 0.001), Depression-hopelessness (p = 0.001) and Guilty idea of reference-pathological guilt (p = 0.03). Considering patients with CDSS>6 (n = 23), compared to sham, active-tDCS significantly improved CDSS total score (p < 0.001), Depression-hopelessness (p = 0.001) but Guilty idea of reference-pathological guilt only marginally improved (p = 0.051). Considering response rates of clinically significant depression, important reductions of CDSS score were observed (78 % of the sample scored ≤6; active-tDCS, n = 23; sham-tDCS, n = 16; p = 0.017). Early wakening item did not significantly change in any group. LIMITATIONS: The study lacks a follow-up period and evaluation of tDCS effects on psychosocial functioning. CONCLUSIONS: Bilateral bipolar-nonbalanced prefrontal tDCS is a successful protocol for the treatment of depressive symptoms in patients with schizophrenia.

The role of pharmacogenetics in the treatment of major depressive disorder: a critical review.

Pharmacological therapy represents one of the essential approaches to treatment of Major Depressive Disorder (MDD). However, currently available antidepressant medications show high rates of first-level treatment non-response, and several attempts are often required to find an effective molecule for a specific patient in clinical practice. In this context, pharmacogenetic analyses could represent a valuable tool to identify appropriate pharmacological treatment quickly and more effectively. However, the usefulness and the practical effectiveness of pharmacogenetic testing currently remains an object of scientific debate. The present narrative and critical review focuses on exploring the available evidence supporting the usefulness of pharmacogenetic testing for the treatment of MDD in clinical practice, highlighting both the points of strength and the limitations of the available studies and of currently used tests. Future research directions and suggestions to improve the quality of available evidence, as well as consideration on the potential use of pharmacogenetic tests in everyday clinical practice are also presented.

Psychological impact of Covid-19 pandemic in mental healthcare workers: a cross-sectional study in an Italian Department of Mental Health.

AIM: The Covid-19 pandemic is having a great impact on the lives of healthcare workers, but its psychological impact on Mental Healthcare Workers (MHWs) remains to be better explored. The aims of the present study were to assess the correlates and predictors of stress and adverse psychological effects in MHWs during the first waves of the Covid-19 pandemic. METHODS: A total of 124 MHWs (psychiatrist/psychiatry resident, nurse, psychologist/psychotherapist, psychiatric rehabilitation therapist/educator, other mental health professional) working in public facilities of the ASST Spedali Civili of Brescia, Italy, was assessed between June 28, 2020 and August 10, 2020 with an online questionnaire that included sociodemographic, professional and Covid-19 exposure information, the Impact of Event Scale - Revised and the Depression Anxiety Stress Scales 21. Multivariate linear regression models were designed to identify individual predictors of post-traumatic, depressive, anxiety and stress-symptoms. RESULTS: The professional role of nurse, having more years of professional experience and experiencing the death of a patient emerged as predictors of more severe post-traumatic symptoms. The professional role of nurse emerged as the only predictor of more severe depressive symptoms; the professional role of nurse and having more years of professional experience emerged as predictors of more severe anxiety symptoms; more years of professional experience, higher workloads, worse team relationships and experiencing the death of a loved one emerged as predictors of more severe stress symptoms. CONCLUSIONS: Alongside other stressful factors, the professional role of nurse and more years of professional experience emerged as predictors of adverse psychological events. Working as a MHW, particularly with high levels of contact with patients during the Covid-19 pandemic, may be considered strenuous work, requiring dedicated training and interventions to improve resilience. KEY WORDS: Anxiety, Covid-19, depression, mental healthcare workers, stress-related disorder, stressful life events.

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.

Life engagement in people living with schizophrenia: predictors and correlates of patient life engagement in a large sample of people living in the community.

BACKGROUND: Life engagement represents a holistic concept that encompasses outcomes reflecting life-fulfilment, well-being and participation in valued and meaningful activities, which is recently gaining attention and scientific interest. Despite its conceptual importance and its relevance, life engagement represents a largely unexplored domain in schizophrenia. The aims of the present study were to independently assess correlates and predictors of patient life engagement in a large and well-characterized sample of schizophrenia patients. METHODS: To assess the impact of different demographic, clinical, cognitive and functional parameters on life engagement in a large sample of patients with schizophrenia, data from the social cognition psychometric evaluation project were analyzed. RESULTS: Overall schizophrenia and depressive symptom severity, premorbid IQ, neurocognitive performance, social cognition performance both in the emotion processing and theory of mind domains, functional capacity, social skills performance and real-world functioning in different areas all emerged as correlates of patient life engagement. Greater symptom severity and greater impairment in real-world interpersonal relationships, social skills, functional capacity and work outcomes emerged as individual predictors of greater limitations in life engagement. CONCLUSIONS: Life engagement in people living with schizophrenia represents a holistic and complex construct, with several different clinical, cognitive and functional correlates. These features represent potential treatment targets to improve the clinical condition and also facilitate the process of recovery and the overall well-being of people living with schizophrenia.

Efficacy of Functional Remediation on Cognitive and Psychosocial Functioning in Patients with Bipolar Disorder: Study Protocol for a Randomized Controlled Study.

BACKGROUND: Neurocognitive impairment is a prominent characteristic of bipolar disorder (BD), linked with poor psychosocial functioning. This study's purpose is to evaluate the effectiveness of functional remediation (FR) in enhancing neurocognitive dysfunctions in a sample of remitted patients with diagnosis of BD in comparison to treatment as usual-TAU. To quantify the neurocognitive damage, the Brief Assessment of Cognition in Affective Disorders (BAC-A) will be used, and the overall psychosocial functioning will be measured with the Functioning Assessment Short Test-FAST. METHODS: The randomized, rater-blinded, controlled study will include two arms (1:1) encompassing 54 outpatients with diagnosis of BD-I and BD-II, as defined by the DSM-5 criteria. In the experimental phase, remitted patients aged 18-55 years will be involved. At the baseline, at the end of intervention and at the 6-month follow-up, patients will be evaluated using clinical scales (Young Mania Rating Scale (Y-MRS) and Hamilton Depression Rating Scale (HAM-D)). Neurocognitive measurements and psychosocial functioning will be valued, respectively, with BAC-A and FAST. DISCUSSION: The primary expected outcome is that following FR intervention, patients will exhibit improved cognitive abilities and psychosocial outcomes compared to the participants in the TAU group. It is now recognized that neurocognitive deficits are potential predictors of functional outcome in patients with BD. In recent years, there has been a growing interest in the implementation of interventions that, in addition to symptomatic remission, are also aimed at neurocognitive dysfunctions in order to achieve a recovery of psychosocial functioning.

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.

Socio-demographic and clinical characteristics of SARS-CoV-2-positive psychiatric in-patients: A case-control study in the psychiatric wards of a Great Metropolitan Hospital in Milan.

During the first Covid-19 outbreak, the Niguarda Hospital of Milan featured two Psychiatry wards, one for SARS-CoV-2 positive patient and one for patients requiring hospitalization and negative for SARS-CoV-2. The two groups of patients were compared and were similar in distribution of psychiatric diagnosis, duration of illness and previous hospitalizations. SARS-CoV-2 positive participants had a lower severity of symptoms both at admission and discharge, a lower frequency of psychotic symptoms and substance intoxication at admission. These findings suggest that patients admitted to the COVID ward were hospitalized not only for their mental health condition but also because of the infection.

Cognitive and clinical characteristics of offenders and non-offenders diagnosed with schizophrenia spectrum disorders: results of the Recoviwel observational study.

The association between schizophrenia spectrum disorders (SSD) and violent behavior is complex and requires further research. The cognitive correlates of violent behavior, in particular, remain to be further investigated. Aims of the present study were to comprehensively assess the cognitive and clinical profile of SSD violent offenders and evaluate individual predictors of violent behavior. Fifty inmates convicted for violent crimes in a forensic psychiatry setting and diagnosed with SSD were compared to fifty non-offender patients matched for age, gender, education, and diagnosis. Offender and non-offender participants were compared based on socio-demographic, clinical, and cognitive variables using non-parametric testing to select potential predictors of violent behavior. Multivariate logistic regressions were then performed to identify individual predictors of violent behavior. Offender participants showed more school failures, higher prevalence of substance use, higher Clinical Global Impression Severity Scale (CGI-S) and Positive and Negative Syndrome Scale Excited Component (PANSS-EC) scores, worse working memory and better attention performance, higher Historical Clinical and Risk Management scale 20 (HCR-20) and Hare Psychopathy Checklist (PCL-R) scores in all subdomains and factors. School failures, higher PANSS-EC scores, worse working memory and processing speed, better attention performance, higher scores in HCR-20 Management subscale and the PCL-R "Callous" factor emerged as predictors of violent behavior. Better attentional performance was correlated with higher PCL-R "Callous" factor scores, worse cognitive performance in several domains with higher PCL-R "Unstable" factor scores. In conclusion, the present study highlights the importance of carefully assessing SSD patients with violent behavior in all clinical, cognitive, and behavioral aspects.

Acceptability of cognitive remediation for schizophrenia: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Acceptability is an important factor for predicting intervention use and potential treatment outcomes in psychosocial interventions. Cognitive remediation (CR) improves cognition and functioning in people with a diagnosis of schizophrenia, but its acceptability, and the impact of participants and treatment characteristics, remain to be investigated. Few studies provide a direct measure of acceptability, but treatment drop-out rates are often available and represent a valid surrogate. METHOD: The systematic search conducted for the most comprehensive CR outcomes database for schizophrenia was updated in December 2020. Eligible studies were randomized clinical trials comparing CR with any other control condition in patients diagnosed with schizophrenia spectrum disorders and that also reported drop-out in treatment and control arms separately. Acceptability was measured as odd-ratios (OR) of drop-out. RESULTS: Of 2119 identified reports, 151 studies, reporting 169 comparisons between CR and control interventions with 10 477 participants were included in the analyses. The overall rate of drop-out was 16.58% for CR programs and 15.21% for control conditions. In the meta-analysis, no difference emerged between CR interventions and controls [OR 1.10, 95% confidence interval (CI) 0.96-1.25, p = 0.177]. Factors improving acceptability were: inpatient only recruitment, participants with fewer years of education and lower premorbid IQ, the presence of all CR core elements, and the presence of techniques to transfer cognitive gains into real-world functioning. CONCLUSIONS: CR for people diagnosed with schizophrenia is effective and has a good acceptability profile, similar to that of other evidence-based psychosocial interventions.

Current Evidence and Theories in Understanding the Relationship between Cognition and Depression in Childhood and Adolescence: A Narrative Review.

The present narrative review has covered the current evidence regarding the role of cognitive impairments during the early phase of major depressive disorder (MDD), attempting to describe the cognitive features in childhood, adolescence and in at-risk individuals. These issues were analyzed considering the trait, scar and state hypotheses of MDD by examining the cold and hot dimensions, the latter explained in relation to the current psychological theoretical models of MDD. This search was performed on several electronic databases up to August 2022. Although the present review is the first to have analyzed both cold and hot cognitive impairments considering the trait, scar and state hypotheses, we found that current evidence did not allow to exclusively confirm the validity of one specific hypothesis since several equivocal and discordant results have been proposed in childhood and adolescence samples. Further studies are needed to better characterize possible cognitive dysfunctions assessing more systematically the impairments of cold, hot and social cognition domains and their possible interaction in a developmental perspective. An increased knowledge on these topics will improve the definition of clinical endophenotypes of enhanced risk to progression to MDD and, to hypothesize preventive and therapeutic strategies to reduce negative influences on psychosocial functioning and well-being.

Primary and secondary negative symptoms severity and the use of psychiatric care resources in schizophrenia spectrum disorders: A 3-year follow-up longitudinal retrospective study.

Negative symptoms represent one of the core features of schizophrenia spectrum disorders (SSD), strongly correlated with low remission rates, poor real-world functioning, and worse quality of life. Despite the body of evidence attesting the role of negative symptoms in determining worse outcomes in SSD, few studies have directly investigated their impact on the use of psychiatric services and even fewer research have examined the differential impact between primary versus secondary negative symptoms. The present study aims to investigate whether SSD subjects with high levels of primary and of secondary negative symptoms at an index hospitalization show a different use of psychiatric services in the subsequent 3 years. A total of 429 subjects were included in the study. Results show that SSD patients with high levels of negative symptoms are characterized by an overall greater use of high-cost resources, with more admissions in the hospital acute care psychiatric ward and in high intensity residential inpatient services. Moreover, while primary negative symptoms appear to play a role in determining a greater use of psychiatric services, high levels of secondary negative symptoms are associated with an increased use of most psychiatric resources, especially of high-cost ones. In conclusion, negative symptoms have a relevant impact on the pattern of psychiatric resources utilization in SSD patients. While scientific research continues to look for effective treatments for primary negative symptoms, clinicians should pay particular attention to secondary negative symptoms, as these also have important consequences but may benefit from appropriate treatment.

Long-acting Injectable Antipsychotics during the COVID-19 pandemic in schizophrenia: An observational study in a real-world clinical setting.

The COVID-19 pandemic is having an important impact on the practice of mental health services and on schizophrenia patients, and heterogeneous and conflicting findings are being reported on the reduction of long-acting injectable (LAI) antipsychotics use. Aims of the study were to assess the total number of patients treated with LAI, the start of novel LAI and the discontinuation of LAI treatments, analyzing register data of the first year of the pandemic, 2020, compared to a pre-pandemic reference year, 2019. Data from two outpatient centers were retrieved, for a total of 236 participants in 2020: no significant differences were observed comparing 2020 and 2019 when considering the total number of patients on LAI treatment (p = 0.890) and the number of dropouts (p = 0.262); however, a significant reduction in the start of LAI was observed (p = 0.022). In 2020, second generation LAI were more prescribed than first generation LAI (p = 0.040) while no difference was observed in 2019 (p = 0.191). These findings attest the efficacy of measures adopted in mental health services to face the consequences of COVID-19 and shed further light on the impact of the pandemic on the clinical practice of mental health services and on the continuity of care of people with schizophrenia.