Improving Quality of Life in Bipolar Disorders with an Immersive Virtual Reality Remediation Training Randomized Controlled Trial (RCT).

Background: Health-related quality of life (H-QoL) is a critical measure in bipolar disorder (BD). Recent trials using virtual reality (VR) have shown potential in improving H-QoL. However, VR's effect on the H-QoL of people with BD needs to be further explored. Methods: This study involved a secondary analysis of a feasibility randomized controlled trial, focusing on "quality of life". Participants (aged 18-75) diagnosed with bipolar disorder were randomized into two groups. The experimental group used the CEREBRUM VR app, while the control group received the usual care. Quality of life was assessed using the Short-Form Health Survey (SF-12). Results: A total of 39 individuals in the experimental group and 25 in the control group represent the final samples. The results showed a greater improvement in the SF-12 total score in the experimental group (8.7%) compared to the control group (F = 66.851 p < 0.0001), specifically in the dimension of physical activity limitation, emotional impact, concentration, pain, calmness, energy levels, discouragement, and social activities. Conclusions: This study demonstrated an improvement in QoL for individuals with BD following a VR intervention. As a feasibility study, this secondary outcome needs to be confirmed by further phase III studies. If confirmed, VR could offer valuable rehabilitation tools and insights into the pathogenesis and treatment of BD.

Symptomatic remission and recovery in major psychosis: Is there a role for BDNF? A secondary analysis of the LABSP cohort data.

Remission, relapse prevention, and clinical recovery are crucial areas of interest in schizophrenia (SCZ) research. Although SCZ is a chronic disorder with poor overall outcomes, years of research demonstrated that recovery is possible. There are considerable data linking brain-derived neurotrophic factor (BDNF) to SCZ, however, evidence on the role of BDNF in remission in SCZ is scarce. This secondary analysis of the Longitudinal Assessment of BDNF in Sardinian patients (LABSP) data aimed to investigate the relationship between serum BDNF levels and symptomatic remission, simultaneous clinical and functional remission, and recovery in patients with SCZ. A total of 105 patients with SCZ or schizoaffective disorder were recruited for a longitudinal assessment of BDNF levels over 24 months. Longitudinal data were analyzed using mixed-effects linear regression models. The study found significant associations between use of long acting injectables (χ2 = 7.075, df = 1, p = 0.008), baseline serum BDNF levels (U = 701, z = -2.543, p = 0.011), and "childhood" (U = 475, z = -2.124, p = 0.034) and "general" (U = 55, z = -2.014, p = 0.044) subscales of the Premorbid Adjustment Scale (PAS) with patients maintaining remission and recovery. The diagnosis of SCZ was significantly associated with lower BDNF levels for patients with simultaneous clinical and functional remission (Z = 2.035, p = 0.0419) and recovery (Z = 2.009, p = 0.0445) compared to those without. There were no significant associations between remission in the entire sample and longitudinal serum BDNF levels or genetic variants within the BDNF gene. These findings provide further insight into the complex relationship between BDNF and SCZ.

Converging Evidence Points to BDNF as Biomarker of Depressive Symptoms in Schizophrenia-Spectrum Disorders.

Brain-derived neurotrophic factor (BDNF) is a key modulator of neuroplasticity and has an important role in determining the susceptibility to severe psychiatric disorder with a significant neurodevelopmental component such as major psychoses. Indeed, a potential association between BDNF serum levels and schizophrenia (SCZ) and schizoaffective disorder (SAD) has been tested in diverse studies and a considerable amount of them found reduced BDNF levels in these disorders. Here, we aimed at testing the association of BDNF serum levels with several demographic, clinical, and psychometric measures in 105 patients with SCZ and SAD, assessing the moderating effect of genetic variants within the BDNF gene. We also verified whether peripheral BDNF levels differed between patients with SCZ and SAD. Our findings revealed that BDNF serum levels are significantly lower in patients affected by SCZ and SAD presenting more severe depressive symptomatology. This finding awaits replication in future independent studies and points to BDNF as a possible prognostic indicator in major psychoses.

Exploring the association between brain-derived neurotrophic factor levels and longitudinal psychopathological and cognitive changes in Sardinian psychotic patients.

BACKGROUND AND HYPOTHESIS: Schizophrenia spectrum disorders are among the most debilitating mental disorders and has complex pathophysiological underpinnings. There is growing evidence that brain-derived neurotrophic factor (BDNF) can play a role in its pathogenesis. The present study investigated the longitudinal variation of serum BDNF levels in a 24-month observational prospective cohort study of Sardinian psychotic patients and its relationship with psychopathological and cognitive changes. Furthermore, we examined whether genetic variation within the BDNF gene could moderate these relationships. STUDY DESIGN: Every 6 months, 105 patients were assessed for their BDNF serum levels, as well as for a series of psychopathological, cognitive, and social measures. We performed a targeted analysis of four tag single nucleotide polymorphisms within the BDNF gene that were selected and analyzed using polymerase chain reaction. Longitudinal data were analyzed using mixed-effects linear regression models. STUDY RESULTS: We observed a declining longitudinal trajectory of BDNF levels in psychotic patients in general, and in relation to the severity of depressive and negative symptoms. BDNF serum levels also declined in patients scoring lower in cognitive measures such as attention and speed of information processing and verbal fluency. The rs7934165 polymorphism moderated the significant association between verbal fluency and BDNF levels. CONCLUSIONS: These findings in patients from real-world settings suggest a plausible role of peripheral BDNF levels as a marker of illness burden in schizophrenia spectrum disorders.

Blood-brain barrier dysfunction in bipolar disorder: Molecular mechanisms and clinical implications.

Bipolar disorder (BD) is a severe psychiatric disorder affecting approximately 1-3% of the population and characterized by a chronic and recurrent course of debilitating symptoms. An increasing focus has been directed to discover and explain the function of Blood-Brain Barrier (BBB) integrity and its association with a number of psychiatric disorders; however, there has been limited research in the role of BBB integrity in BD. Multiple pathways may play crucial roles in modulating BBB integrity in BD, such as inflammation, insulin resistance, and alterations of neuronal plasticity. In turn, BBB impairment is hypothesized to have a significant clinical impact in BD patients. Based on the high prevalence of medical and psychiatric comorbidities in BD and a growing body of evidence linking inflammatory and neuroinflammatory mechanisms to the disorder, recent studies have suggested that BBB dysfunction may play a key role in BD's pathophysiology. In this comprehensive narrative review, we aim to discuss studies investigating biological markers of BBB in patients with BD, mechanisms that modulate BBB integrity, their clinical implications on patients, and key targets for future development of novel therapies.

Mixed Depression: A Mini-Review to Guide Clinical Practice and Future Research Developments.

The debate on mixed states (MS) has been intense for decades. However, several points remain controversial from a nosographic, diagnostic, and therapeutic point of view. The different perspectives that have emerged over the years have turned into a large, but heterogeneous, literature body. The present review aims to summarize the evidence on MS, with a particular focus on mixed depression (MxD), in order to provide a guide for clinicians and encourage the development of future research on the topic. First, we review the history of MS, focusing on their different interpretations and categorizations over the centuries. In this section, we also report alternative models to traditional nosography. Second, we describe the main clinical features of MxD and list the most reliable assessment tools. Finally, we summarize the recommendations provided by the main international guidelines for the treatment of MxD. Our review highlights that the different conceptualizations of MS and MxD, the variability of clinical pictures, and the heterogeneous response to pharmacological treatment make MxD a real challenge for clinicians. Further studies are needed to better characterize the phenotypes of patients with MxD to help clinicians in the management of this delicate condition.

Sustained symptomatic remission in schizophrenia: Course and predictors from a two-year prospective study.

BACKGROUND: Although remission is a priority target in psychosis, reported rates show a marked variation across studies and instability over time. Such variability, partly due to methodology, emphasizes the need to define the optimal assessment procedure, as well as to identify reliable predictors. This study aims to: 1. longitudinally compare remission status according to different criteria; 2. identify predictors of duration and stability. METHODS: 112 patients with schizophrenia or schizoaffective disorder underwent comprehensive clinical evaluations, with 24-month follow-up. Remission was assessed using three criteria: Remission in Schizophrenia Working Group (RSWG) vs Positive and Negative Syndrome Scale (PANSS) positive and negative scales (PANSS-PN) vs total score (PANSS-T). Kaplan-Meier survival analysis was used for longitudinal comparison, regression models to identify predictors of duration and stability. RESULTS: At enrolment 50% of patients were in remission according to RSWG, while only 23.2% reached the other criteria. PANSS-T cumulative remission rates showed the greatest stability. Stable remission according to RSWG criteria was predicted by negative symptoms, while no significant predictors emerged for PANSS-T. Remission duration was predicted by negative, positive and cognitive symptoms and treatment dosage for RSWG criteria, while for PANSS-T the predictors were cognitive symptoms and duration of illness. CONCLUSION: Results are in line with previous literature on remission rates and further support the role of basal clinical predictors. In addition, this study shows that more stringent criteria are more stable over time, suggesting their predictive value and the relevance of their use to optimize evaluations also in clinical settings.

Renaming schizophrenia? A survey among psychiatrists, mental health service users and family members in Italy.

This survey explores how psychiatrists, service users and family members in Italy perceive the term schizophrenia and if they consider a name change a useful option in order to overcome the stigma attached to it. Opinions on the term schizophrenia were collected by a self-rated questionnaire used in previous international surveys. Questionnaires were delivered members of the Italian Psychiatric Association. Survey of mental health users was conducted among members of the main users' association of the Veneto region; survey of family members was conducted among one of the most representative Italian family association. Overall, 350 psychiatrists, 71 mental health users and 110 family members filled in the questionnaires. Considering the whole sample, 41.5% found the term inappropriate, 67.6% stigmatizing and 72.3% advocated a name change. Among psychiatrists 57% reported that schizophrenia was inappropriate, 70% considered the term stigmatizing and 71% was in favor of a name change. Similarly, 56% of service users and 71% of family members found schizophrenia a stigmatizing term and, respectively, 75% and 77% advocated a name change. Conflicting results were found on possible alterative terms: psychiatrists proposed a wide range of possible options, most of which referred to the term 'psychosis' (53%), whereas users and family members preferred terms referring to the broad category of 'mental health suffering'. Overall, most of respondents in the three stakeholders' groups agree that schizophrenia should be renamed to reduce the stigma attached to it; the main challenge, however, is the lack of consensus on the best alternative term to use.

Psychiatry during the Covid-19 pandemic: a survey on mental health departments in Italy.

BACKGROUND: To date, very few nationwide studies addressing the way in which mental health services are addressing the current pandemics have been published. The present paper reports data obtained from a survey relating to the Italian mental health system conducted during the first phase of the Covid-19 epidemic. METHODS: Two online questionnaires regarding Community Mental Health Centres (CMHC) and General Hospital Psychiatric Wards (GHPW), respectively, were sent to the Heads of all Italian Mental Health Departments (MHDs). Statistical analysis was carried out by means of Chi Square test with Yates correction or the Fisher Exact test, as needed. RESULTS: Seventy-one (52.9%) of the 134 MHDs and 107 (32.6%) of the 318 GHPWs returned completed questionnaires. Less than 20% of CMHCs were closed and approx. 25% had introduced restricted access hours. A substantial change in the standard mode of operation in CMHCs was reported with only urgent psychiatric interventions, compulsory treatments and consultations for imprisoned people continuing unchanged. All other activities had been reduced to some extent. Remote contacts with users had been set up in about 75% of cases. Cases of COVID positivity were reported for both staff members (approx. 50% of CHMCs) and service users (52% of CHMCs). 20% of CMHCs reported cases of increased aggressiveness or violence among community patients, although only 8.6% relating to severe cases. Significant problems emerged with regard to the availability of personal protective equipment (PPE) for staff members. A reduced number of GHPWs (- 12%), beds (approx.-30%) and admissions were registered (87% of GHPWs). An increase in compulsory admissions and the rate of violence towards self or others among inpatients was reported by 8% of GHPWs. Patient swabs were carried out in 50% of GHPWs. 60% of GHPWs registered the admission to general COVID-19 Units of symptomatic COVID+ non-severe psychiatric patients whilst COVID+ severe psychiatric patients who were non-collaborative were admitted to specifically set up "COVID-19" GHPWs or to isolated areas of the wards purposely adapted for the scope. CONCLUSIONS: The pandemic has led to a drastic reduction in levels of care, which may produce a severe impact on the mental health of the population in relation to the consequences of the expected economic crisis and of the second ongoing wave of the pandemic.

Vaping effects on asthma: results from a web survey and clinical investigation.

It is well known that tobacco smoking worsens asthma. Conversely, few data are currently available in the literature on the effects of vaping in asthmatic patients. This work aims to investigate the effects of vaping on asthmatic patients and in asthmatic patients that switched from tobacco smoking to electronic cigarette (e-cig), in particular focusing on quality of life, asthma control, and pulmonary function. We designed a two-group study. One group encompassed vapers with asthma selected through a web survey with questions on quality of life and symptoms worsening; the other group encompassed vapers that switched from tobacco smoking to e-cig, and that volunteered to undergo clinical visits at our outpatient clinic. 2787 people responded to the web survey, including 631 asthmatics. In the second group, 55 volunteers, including 15 asthmatics, were enrolled after a visit. The visit included physical examination and pulmonary function tests (PFT). Internationally validated questionnaires were administered to all subjects: Asthma Control Test (ACT), Asthma Control Questionnaire (ACQ), 36-Item Short Form Survey (SF-36) and Asthma Quality of Life Questionnaire (AQLQ). The 382 asthmatic vapers-only in the web survey were mainly males (86.9%), 31-65 years old. 90% of them declared that vaping did not worsen asthma symptoms and would recommend asthmatic smokers to switch to vaping (98.4%). There was worsening of asthma symptoms due to the actual asthma therapy used by the participants, while no relationship was found with other aspects analysed. In the second group, the analysis of variance in the questionnaires administered to the 10 asthmatics showed a significant improvement in ACQ, ACT and SF-36 for asthmatics that switched from tobacco to vaping, while PFT remained stable throughout the three visits. Almost all of the asthmatics who previously smoked would recommend switching to e-cig, and vaping did not worsen their asthma symptoms. Furthermore, switching from tobacco smoking to e-cigs showed a significant improvement in asthma control and quality of life, not showing, in the period studied, to affect pulmonary function tests.

Longitudinal assessment of brain-derived neurotrophic factor in Sardinian psychotic patients (LABSP): a protocol for a prospective observational study.

INTRODUCTION: Brain-derived neurotrophic factor (BDNF) plays a crucial role in neurodevelopment, synaptic plasticity and neuronal function and survival. Serum and plasma BDNF levels are moderately, but consistently, decreased in patients with schizophrenia (SCZ) compared with healthy controls. There is a lack of knowledge, however, on the temporal manifestation of this decline. Clinical, illness course and treatment factors might influence the variation of BDNF serum levels in patients with psychosis. In this context, we propose a longitudinal study of a cohort of SCZ and schizophrenic and schizoaffective disorder (SAD) Sardinian patients with the aim of disentangling the relationship between peripheral BDNF serum levels and changes of psychopathology, cognition and drug treatments. METHODS AND ANALYSIS: Longitudinal assessment of BDNF in Sardinian psychotic patients (LABSP) is a 24-month observational prospective cohort study. Patients with SAD will be recruited at the Psychiatry Research Unit of the Department of Medical Science and Public Health, University of Cagliari and University of Cagliari Health Agency, Cagliari, Italy. We will collect BDNF serum levels as well as sociodemographic, psychopathological and neurocognitive measures. Structured, semistructured and self-rating assessment tools, such as the Positive and Negative Syndrome Scale for psychopathological measures and the Brief Assessment of Cognition in Schizophrenia for cognitive function, will be used. ETHICS AND DISSEMINATION: This study protocol was approved by the University of Cagliari Health Agency Ethics Committee (NP2016/5491). The study will be conducted in accordance with the principles of good clinical practice, in the Declaration of Helsinki in compliance with the regulations. Participation will be voluntary and written informed consent will be obtained for each participant upon entry into the study. We plan to disseminate the results of our study through conference presentations and publication in international peer-reviewed journals. Access to raw data will be available in anonymised form upon request to the corresponding author.

Violence and mental disorders. A retrospective study of people in charge of a community mental health center.

BACKGROUND: Numerous studies conducted in inpatient settings have highlighted how mental disorders are associated with an increased risk of violence, particularly during acute phases. However, to date a more limited number of studies have been performed to assess the risk of violence in outpatients, particularly in Italy. The present study aims to evaluate the prevalence of violent events in a sample of patients in charge of a community mental health center in Italy. METHODS: Based on data obtained from standardized clinical records, a retrospective study was undertaken to investigate acts of violence (physical aggression only) in a total of 678 patients (Males=308, 45.4%) in charge of a university mental health center; patients were mainly affected by anxiety disorders (30.7%), depressive disorder (17.2%), bipolar disorder (18.3%) and schizophrenia or other psychotic disorders (25.0%). RESULTS: 27.6% of the sample had committed at least one act of violence during their lifetime, 10.5% over the previous year. 56.7% of those who committed violence acts had acted violently twice or more during their lifetime. A significant association of lifetime violence was found with gender (male), younger age, low education, unemployment, living with parents. With regard to diagnosis, a significant association was found with schizophrenia and other psychotic disorders, personality disorders, mental retardation, and comorbidity between two or more psychiatric disorders. Violence was moreover associated with early age at onset and at first psychiatric treatment, longer duration of the disorder, previous hospital admissions, previous violent events. CONCLUSION: Violent behavior is relatively common among outpatients.

Assessment of functioning in patients with schizophrenia and schizoaffective disorder with the Mini-ICF-APP: a validation study in Italy.

BACKGROUND: The aim of the study was to evaluate validity of the Italian Mini-ICF-APP (Mini-ICF Rating for Limitations of Activities and Participation in Psychological Disorders) in schizophrenia and related disorders. METHODS: 74 outpatients affected by schizophrenia or schizoaffective disorders attending a University-based community mental health centre were recruited to the study. All participants underwent comprehensive evaluation using standardized instruments to assess clinical, neurocognitive and functional status. Concurrent validity of Mini-ICF-APP was evaluated and compared to severity scores obtained using the Clinical Global Impression-Schizophrenia scale (CGI-SCH), Positive and Negative Syndrome scale (PANSS), Mini Mental State Examination test (MMSE), Brief Assessment of Cognition in Schizophrenia scale (BACS) and Personal and Social Performance scale (PSP). Construct validity was evaluated by comparing scores obtained at Mini-ICF-APP by remitted versus non-remitted patients, and by recovered versus unrecovered patients. Discriminant validity was evaluated comparing scores on Mini-ICF-APP and Subjective Well-being (SWN) scale. RESULTS: the total score and 12 out of the 13 Mini-ICF-APP items correlated significantly with total score at PSP; Mini-ICF-App total score was moreover significantly correlated with total scores at CGI-SCH, PANSS, MMSE, as well as with several BACS items. Total scores obtained at Mini-ICF-APP were significantly higher among remitted and recovered patients. No relevant correlations were found between scores of Mini-ICF-APP and SWN scales. RESULTS: The total score and 12 out of the 13 Mini-ICF-APP items correlated significantly with total score at PSP; Mini-ICF-App total score was moreover significantly correlated with total scores at CGI-SCH, PANSS, MMSE, as well as with several BACS items. Total scores obtained at Mini-ICF-APP were significantly higher among remitted and recovered patients. No relevant correlations were found between scores of Mini-ICF-APP and SWN scales. CONCLUSION: the Italian version of Mini-ICF-APP is a valid instrument for use in evaluating functioning in chronic patients with schizophrenia and related disorders.

Clinical Global Impression-severity score as a reliable measure for routine evaluation of remission in schizophrenia and schizoaffective disorders.

AIMS: This study aimed to compare the performance of Positive and Negative Syndrome Scale (PANSS) symptom severity criteria established by the Remission in Schizophrenia Working Group (RSWG) with criteria based on Clinical Global Impression (CGI) severity score. The 6-month duration criterion was not taken into consideration. METHODS: A convenience sample of 112 chronic psychotic outpatients was examined. Symptomatic remission was evaluated according to RSWG severity criterion and to a severity criterion indicated by the overall score obtained at CGI-Schizophrenia (CGI-SCH) rating scale (≤3) (CGI-S). RESULTS: Clinical remission rates of 50% and 49.1%, respectively, were given by RSWG and CGI-S, with a significant level of agreement between the two criteria in identifying remitted and non-remitted cases. Mean scores at CGI-SCH and PANSS scales were significantly higher among remitters, independent of the remission criteria adopted. Measures of cognitive functioning were largely independent of clinical remission evaluated according to both RSWG and CGI-S. When applying RSWG and CGI-S criteria, the rates of overall good functioning yielded by Personal and Social Performance scale (PSP) were 32.1% and 32.7%, respectively, while the mean scores at PSP scale differed significantly between remitted and non-remitted patients, independent of criteria adopted. The proportion of patients judged to be in a state of well-being on Social Well-Being Under Neuroleptics-Short Version scale (SWN-K) were, respectively, 66.1% and 74.5% among remitters according to RSWG and CGI-S; the mean scores at the SWN scale were significantly higher only among remitters according to CGI-S criteria. CONCLUSIONS: CGI severity criteria may represent a valid and user-friendly alternative for use in identifying patients in remission, particularly in routine clinical practice.