Clinical and psychological factors associated with resilience in patients with schizophrenia: data from the Italian network for research on psychoses using machine learning.

BACKGROUND: Resilience is defined as the ability to modify thoughts to cope with stressful events. Patients with schizophrenia (SCZ) having higher resilience (HR) levels show less severe symptoms and better real-life functioning. However, the clinical factors contributing to determine resilience levels in patients remain unclear. Thus, based on psychological, historical, clinical and environmental variables, we built a supervised machine learning algorithm to classify patients with HR or lower resilience (LR). METHODS: SCZ from the Italian Network for Research on Psychoses (N = 598 in the Discovery sample, N = 298 in the Validation sample) underwent historical, clinical, psychological, environmental and resilience assessments. A Support Vector Machine algorithm (based on 85 variables extracted from the above-mentioned assessments) was built in the Discovery sample, and replicated in the Validation sample, to classify between HR and LR patients, within a nested, Leave-Site-Out Cross-Validation framework. We then investigated whether algorithm decision scores were associated with the cognitive and clinical characteristics of patients. RESULTS: The algorithm classified patients as HR or LR with a Balanced Accuracy of 74.5% (p < 0.0001) in the Discovery sample, and 80.2% in the Validation sample. Higher self-esteem, larger social network and use of adaptive coping strategies were the variables most frequently chosen by the algorithm to generate decisions. Correlations between algorithm decision scores, socio-cognitive abilities, and symptom severity were significant (pFDR < 0.05). CONCLUSIONS: We identified an accurate, meaningful and generalizable clinical-psychological signature associated with resilience in SCZ. This study delivers relevant information regarding psychological and clinical factors that non-pharmacological interventions could target in schizophrenia.

Two-Injection Start Regimen of Long-Acting Aripiprazole in 133 Patients With Schizophrenia.

PURPOSE/BACKGROUND: Based on a population-pharmacokinetic model, the European Medicines Agency has recently approved a simplified starting strategy of aripiprazole once a month (AOM), injectable and long-acting antipsychotic, with two 400 mg injections and a single oral 20 mg dose of aripiprazole, administered on the same day, instead of 1 injection and 14 daily administrations of concurrent oral aripiprazole. However, to our knowledge, no previous study has reported the safety and tolerability of this regimen in real-world patients. METHODS/PROCEDURES: We retrospectively reviewed medical records of 133 patients who received the newly approved 2-injection start regimen as part of their standard care in 10 Italian clinical centers. FINDINGS/RESULTS: Adverse effects were mild or moderate, with no clinically evident difference from the adverse effects observed in previous trials where AOM was started with a single injection followed by 14 days of orally administered aripiprazole. None of the patients who started AOM after the 2-injection start regimen experienced severe adverse effects or severe adverse effects. IMPLICATIONS/CONCLUSIONS: The coadministration of 2 injections of 400 mg aripiprazole and 20 mg oral aripiprazole was not associated with safety concerns beyond those reported after a single injection followed by 14 days of orally administered aripiprazole. Our results should be interpreted with caution, due to the limited sample size and to the retrospective design of the study.

Catatonia-like behavior and immune activation: a crosstalk between psychopathology and pathology in schizophrenia.

BACKGROUND: In Kalhbaum's first characterization of catatonia, the emotional symptoms, such as decreased or restricted expression of feelings and emotions, which is described as blunted affect, are related to the motor symptoms. In later years, the affective domain was excluded from the concept of catatonia and was not included among the diagnostic criteria in the various Diagnostic Statistical Manual (DSM) versions. In recent times, some authors have proposed the proposition of reevaluating the notion of catatonia through the reintroduction of the affective domain. The objective of this study was to examine the correlation between catatonic-like behavior (CLB), such as emotional withdrawal, blunted affect, and psychomotor slowing, and inflammatory markers, namely the neutrophil/lymphocytes ratio (NLR) and lymphocytes/monocytes ratio (LMR), in individuals diagnosed with schizophrenia. METHOD: A sample of 25 patients with schizophrenia (10 females, 15 males) was recruited, and the Brief Psychiatric Rating Scale (BPRS) was used to assess the severity of emotional withdrawal, blunted affect, and psychomotor slowing. FINDINGS: The correlation analysis (Spearman ρ) revealed a robust direct association between blunted affect and psychomotor slowing (ρ = 0.79, P = 0.001), and a significant direct correlation between CLB (emotional withdrawal, ρ = 0.51, P = 0.05; blunted affect ρ = 0.58, P = 0.05; motor retardation, ρ = 0.56, P = 0.05) and LMR (ρ = 0.53, P = 0.05). In addition, patients with a duration of illness (DOI) older than five years had a higher presence of CLB and a higher LMR than patients with a more recent diagnosis of the disease. Likely, patients with positive symptoms and in the prodromal and active stages of the disease have a different immune profile than patients in the residual stage and with a predominance of negative symptoms. CONCLUSIONS: Psychomotor slowing and blunted affect are two significantly related features, representing the two-faced Janus of immobility. Furthermore, aggregating them in CLB is more predominant the longer the duration of schizophrenia and is associated with different a specific pattern of immune activation.

A Systematic Review on the Effect of Nutraceuticals on Antidepressant-Induced Sexual Dysfunctions: From Basic Principles to Clinical Applications.

Sexual dysfunctions are common side effects reported by patients during antidepressant treatment. When they occur, patients often discontinue psychopharmacological therapy, with a negative impact on the underlying psychiatric disease. Recently, great attention has been paid to the use of nutraceuticals in the management of psychiatric disorders, although a systematic review on their effects as a treatment option for antidepressant-induced sexual dysfunctions (AISD) is lacking. Here, we conducted a systematic search in the following databases: MEDLINE (through PubMed), EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, and Web of Science. We searched eligible studies among parallel or crossover randomized controlled trials (RCTs) in adult populations. After this process, a total of 10 articles that evaluated the effect of six different nutraceuticals versus placebo were included: Maca Root, S-adenosyl-L-methionine (SAMe), Rosa Damascena, Ginkgo Biloba, Saffron, and Yohimbine. Overall, a high dose of Maca Root and the use of SAMe or Saffron may improve AISD. Additionally, the administration of Rosa Damascena seemed to be more effective in men than in women, whereas no evidence of effects emerged for Gingko Biloba and Yohimbine. Given the mixed results still available, future RCTs should consider larger samples and confounding factors, such as depressive status and individual vulnerability.

Which mixed depression model? A comparison between DSM-5-defined mixed features and Koukopoulos' criteria.

BACKGROUND: The criteria of the Diagnostic and Statistical Manual of Mental Disorders 5th edition "with mixed features specifier" (DSM-5 MFS) are considered controversial since they include only typical manic symptoms. By contrast, Koukopoulos developed an alternative model of mixed depression (MxD) focusing primarily on the excitatory component. OBJECTIVE: To compare DSM-5 MFS and Koukopoulos' MxD (KMxD) in terms of prevalence, associated clinical variables, and discriminative capacity for bipolar depression in patients with major depressive episode (MDE). METHODS: A total of 300 patients with MDE-155 with major depressive disorder and 145 with bipolar disorder (BD)-were recruited. The discriminative capacity of DSM-5 MFS and KMxD criteria for BD was estimated using the area under the curves of receiver operating characteristic (ROC_AUC). The clinical variables associated with these two diagnostic constructs were assessed by performing a logistic regression. RESULTS: A total of 44 and 165 patients met the DSM-5 MFS and KMxD criteria, respectively. The ROC_AUCs and their confidence intervals for BD according to DSM-5 MFS and KMxD were 77.0% (72.0%-82.1%) and 71.9% (66.2%-77.7%), respectively. The optimal thresholds (combining sensitivity and specificity measures) for BD diagnosis were ≥1 (77%/68%) for DSM-5 MFS and ≥3 symptoms (78%/66%) for KMxD. However, considering the DSM-5 MFS cut-off (≥3 symptoms), the specificity (97%) increased at the expense of sensitivity (26%). CONCLUSIONS: KMxD and DSM-5-MFS showed an overlapping discriminative capacity for bipolar depression. The current diagnostic threshold of DSM-5 MFS did not prove to be very inclusive, if compared with the greater diagnostic sensitivity of KMxD, which also yielded better association with clinical variables related to mixedness.

The effect of cocoa-rich products on depression, anxiety, and mood: A systematic review and meta-analysis.

In the popular imaginary, cocoa-derived products, like chocolate, represent a panacea for mood and affectivity. However, whether this is a myth or a fact has yet to be clarified. A systematic review and meta-analysis were conducted according to the PRISMA guidelines to investigate the effect of cocoa-derived food on depressive and anxiety symptoms, positive and negative affect. We searched Web of KnowledgeTM and PsycINFO up to April 3, 2020. After screening 761 records, we selected nine studies. Two trials evaluated the long-term effects of cocoa consumption (>1 week), two studies the short-term effects (3 days), while five studies were conducted in acute (single administration). Random-effects meta-analyses found an overall significant effect of cocoa-rich products on depressive (Hedge's g = -0.42, 95% CI -0.67 to -0.17) and anxiety symptoms (Hedge's g = -0.49, 95% CI -0.78 to -0.19). Moreover, both positive (Hedge's g = 0.41, 95% CI 0.06 to 0.77) and negative affect (Hedge's g = -0.47, 95% CI -0.91 to -0.03) significantly improved. In all meta-analyses, the effect size was medium, while heterogeneity was low. Our findings suggest that the consumption of cocoa-rich products may improve affect and mood in the short term. However, given the short duration of trials, our results cannot be generalized to long-term intake of cocoa-derived food. Cautious interpretation is also needed due to the low number of participants and studies included in the meta-analyses.

Missed diagnoses and misdiagnoses of adults with autism spectrum disorder.

Autism spectrum disorder (ASD) is a group of life-long neurodevelopmental disorders affecting 1.5% of the general population. The present study aimed to evaluate the psychiatric history of a group of adults who received the first diagnosis of ASD in two Italian university centers. Diagnoses of ASD were confirmed by a team of psychiatrists with wide expertise in the field, after the administration of standardized tools (i.e., ADOS-2, ADI-R). The sample comprised 161 participants, of which 114 (79.5%) were males. The median age of diagnosis was 23 years (range 18-55), with a median IQ of 100 (range 30-145). The first evaluation by a mental health professional was performed at a median age of 13 years, with a gap of 11 years between the first evaluation and the diagnosis of ASD. 33.5% of participants had never received a psychiatric diagnosis, while the rest of the sample had received one or more diagnoses different from ASD. The most common past diagnoses were intellectual disability, psychoses, personality disorders, and depression. Sex differences were detected in the age of diagnosis and ADOS-2 scores. Our results provide important information for both child and adult psychiatrists. Given the prevalence of autism and the high rates of co-occurrent psychiatric conditions, it is important for clinicians to consider ASD in the differential diagnostic process.

Factors Associated with Medication Adherence to Long-Acting Injectable Antipsychotics: Results from the STAR Network Depot Study.

INTRODUCTION: Long-acting injectable (LAI) antipsychotics are prescribed to people with severe psychiatric disorders who show poor adherence to oral medication. The present paper examined factors potentially associated with medication adherence to LAI treatment. METHODS: The STAR (Servizi Territoriali Associati per la Ricerca) Network Depot Study was a multicenter, observational, prospective study that enrolled 461 subjects initiating a LAI from 32 Italian centers. After 6 and 12 months of treatment, we evaluated differences between participants with high (≥5 points) and low (<5 points) medication adherence using Kemp's 7-point scale in sociodemographic, clinical, psychopathological, and drug-related variables. Factors that differed significantly between the two groups were entered for multivariate logistic regression. RESULTS: Six months after enrollment, participants with high medication adherence were younger, living with other people, had lower Brief Psychiatric Rating Scale (BPRS) total scores, lower adverse events, and a more positive attitude toward medication than participants with low adherence. Multivariate regression confirmed lower BPRS resistance and activation scores, absence of adverse events, and positive attitude toward medication as factors significantly associated with good adherence. After 12 months, all BPRS subscales were significantly lower in the high adherence group, which also showed a more positive attitude toward medication. BPRS resistance and attitude toward medication were confirmed as factors associated with medication adherence. DISCUSSION: Our findings suggest that adherence to LAI is principally related to attitude toward medication and traits of suspiciousness/hostility. Quality of patient-clinician relationship and tailored psychoeducational strategies may positively affect adherence in people undergoing psychopharmacological treatment, including LAI.

Antipsychotic polypharmacy reduction versus polypharmacy continuation for people with schizophrenia.

BACKGROUND: In clinical practice, different antipsychotics can be combined in the treatment of people with schizophrenia (polypharmacy). This strategy can aim at increasing efficacy, but might also increase the adverse effects due to drug-drug interactions. Reducing polypharmacy by withdrawing one or more antipsychotics may reduce this problem, but must be done carefully, in order to maintain efficacy. OBJECTIVES: To examine the effects and safety of reducing antipsychotic polypharmacy compared to maintaining people with schizophrenia on the same number of antipsychotics. SEARCH METHODS: On 10 February 2021, we searched the Cochrane Schizophrenia Group's Study-Based Register of Trials, which is based on CENTRAL, CINAHL, ClinicalTrials.Gov, Embase, ISRCTN, MEDLINE, PsycINFO, PubMed and WHO ICTRP. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared reduction in the number of antipsychotics to continuation of the current number of antipsychotics. We included adults with schizophrenia or related disorders who were receiving more than one antipsychotic and were stabilised on their current treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently screened all the identified references for inclusion, and all the full papers. We contacted study authors if we needed any further information. Two review authors independently extracted the data, assessed the risk of bias using RoB 2 and the certainty of the evidence using the GRADE approach. The primary outcomes were: quality of life assessed as number of participants with clinically important change in quality of life; service use assessed as number of participants readmitted to hospital and adverse effects assessed with number of participants leaving the study early due to adverse effects. MAIN RESULTS: We included five RCTs with 319 participants. Study duration ranged from three months to one year. All studies compared polypharmacy continuation with two antipsychotics to polypharmacy reduction to one antipsychotic.  We assessed the risk of bias of results as being of some concern or at high risk of bias. A lower number of participants left the study early due to any reason in the polypharmacy continuation group (risk ratio (RR) 0.44, 95% confidence interval (CI) 0.29 to 0.68; I2 = 0%; 5 RCTs, n = 319; low-certainty evidence), and a lower number of participants left the study early due to inefficacy (RR 0.21, 95% CI 0.07 to 0.65; I2 = 0%; 3 RCTs, n = 201).  Polypharmacy continuation resulted in more severe negative symptoms (MD 3.30, 95% CI 1.51 to 5.09; 1 RCT, n = 35). There was no clear difference between polypharmacy reduction and polypharmacy continuation on readmission to hospital, leaving the study early due to adverse effects, functioning, global state, general mental state and positive symptoms, number of participants with at least one adverse effect, weight gain and other specific adverse effects, mortality and cognition. We assessed the certainty of the evidence as very low or low across measured outcomes. No studies reported quality of life, days in hospital, relapse, depressive symptoms, behaviour and satisfaction with care. Due to lack of data, it was not possible to perform some planned sensitivity analyses, including one controlling for increasing the dose of the remaining antipsychotic. As a result, we do not know if the observed results might be influenced by adjustment of dose of remaining antipsychotic compound. AUTHORS' CONCLUSIONS: This review summarises the latest evidence on polypharmacy continuation compared with polypharmacy reduction. Our results show that polypharmacy continuation might be associated with a lower number of participants leaving the study early, especially due to  inefficacy. However, the evidence is of low and very low certainty and the data analyses based on few study only, so that it is not possible to draw strong conclusions based on the results of the present review. Further high-quality RCTs are needed to investigate this important topic.

Antipsychotic dose reduction compared to dose continuation for people with schizophrenia.

BACKGROUND: Antipsychotic drugs are the mainstay treatment for schizophrenia, yet they are associated with diverse and potentially dose-related side effects which can reduce quality of life. For this reason, the lowest possible doses of antipsychotics are generally recommended, but higher doses are often used in clinical practice. It is still unclear if and how antipsychotic doses could be reduced safely in order to minimise the adverse-effect burden without increasing the risk of relapse. OBJECTIVES: To assess the efficacy and safety of reducing antipsychotic dose compared to continuing the current dose for people with schizophrenia. SEARCH METHODS: We conducted a systematic search on 10 February 2021 at the Cochrane Schizophrenia Group's Study-Based Register of Trials, which is based on CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, PubMed, ClinicalTrials.gov, ISRCTN, and WHO ICTRP. We also inspected the reference lists of included studies and previous reviews. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing any dose reduction against continuation in people with schizophrenia or related disorders who were stabilised on their current antipsychotic treatment.  DATA COLLECTION AND ANALYSIS: At least two review authors independently screened relevant records for inclusion, extracted data from eligible studies, and assessed the risk of bias using RoB 2. We contacted study authors for missing data and additional information. Our primary outcomes were clinically important change in quality of life,  rehospitalisations and dropouts due to adverse effects; key secondary outcomes were clinically important change in functioning, relapse, dropouts for any reason, and at least one adverse effect. We also examined scales measuring symptoms, quality of life, and functioning as well as a comprehensive list of specific adverse effects. We pooled outcomes at the endpoint preferably closest to one year. We evaluated the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 25 RCTs, of which 22 studies provided data with 2635 participants (average age 38.4 years old). The median study sample size was 60 participants (ranging from 18 to 466 participants) and length was 37 weeks (ranging from 12 weeks to 2 years). There were variations in the dose reduction strategies in terms of speed of reduction (i.e. gradual in about half of the studies (within 2 to 16 weeks) and abrupt in the other half), and in terms of degree of reduction (i.e. median planned reduction of 66% of the dose up to complete withdrawal in three studies). We assessed risk of bias across outcomes predominantly as some concerns or high risk.  No study reported data on the number of participants with a clinically important change in quality of life or functioning, and only eight studies reported continuous data on scales measuring quality of life or functioning. There was no difference between dose reduction and continuation on scales measuring quality of life (standardised mean difference (SMD) -0.01, 95% confidence interval (CI) -0.17 to 0.15, 6 RCTs, n = 719, I2 = 0%, moderate certainty evidence) and scales measuring functioning (SMD 0.03, 95% CI -0.10 to 0.17, 6 RCTs, n = 966, I2 = 0%, high certainty evidence). Dose reduction in comparison to continuation may increase the risk of rehospitalisation based on data from eight studies with estimable effect sizes; however, the 95% CI does not exclude the possibility of no difference (risk ratio (RR) 1.53, 95% CI 0.84 to 2.81, 8 RCTs, n = 1413, I2 = 59% (moderate heterogeneity), very low certainty evidence). Similarly, dose reduction increased the risk of relapse based on data from 20 studies (RR 2.16, 95% CI 1.52 to 3.06, 20 RCTs, n = 2481, I2 = 70% (substantial heterogeneity), low certainty evidence).   More participants in the dose reduction group in comparison to the continuation group left the study early due to adverse effects (RR 2.20, 95% CI 1.39 to 3.49, 6 RCTs with estimable effect sizes, n = 1079, I2 = 0%, moderate certainty evidence) and for any reason (RR 1.38, 95% CI 1.05 to 1.81, 12 RCTs, n = 1551, I2 = 48% (moderate heterogeneity), moderate certainty evidence). Lastly, there was no difference between the dose reduction and continuation groups in the number of participants with at least one adverse effect based on data from four studies with estimable effect sizes (RR 1.03, 95% CI 0.94 to 1.12, 5 RCTs, n = 998 (4 RCTs, n = 980 with estimable effect sizes), I2 = 0%, moderate certainty evidence).  AUTHORS' CONCLUSIONS: This review synthesised the latest evidence on the reduction of antipsychotic doses for stable individuals with schizophrenia. There was no difference between dose reduction and continuation groups in quality of life, functioning, and number of participants with at least one adverse effect. However, there was a higher risk for relapse and dropouts, and potentially for rehospitalisations, with dose reduction. Of note, the majority of the trials focused on relapse prevention rather potential beneficial outcomes on quality of life, functioning, and adverse effects, and in some studies there was rapid and substantial reduction of doses. Further well-designed RCTs are therefore needed to provide more definitive answers.

Prevalence and Factors Associated With PTSD-Like Symptoms Linked to the COVID-19 Pandemic Among Patients With Major Depressive Disorders Seeking Emergency Care.

ABSTRACT: The aim of this study was to evaluate the psychological impact and coping strategies experienced by depressed inpatients during the second wave of the COVID-19 pandemic in Italy. We recruited 75 depressed inpatients. Logistic regression was used to determine predictors of PTSD-like symptoms measured with Impact of Event Scale-Revised. Predicting variables were age, sex, the Coping Orientation to Problems Experienced subscales scores, the Anxiety Status Inventory total score, and the Patient Health Questionnaire-9 total score. The prevalence of PTSD-like stress symptoms was 41.33%. Age, social and avoidance coping strategies, and anxiety levels were significant predictors of PTSD-like symptoms. Our findings suggest that the COVID-19 pandemic in depressed inpatients is associated with PTSD-like stress symptoms, anxiety, and maladaptive coping.

Polygenic risk scores for predicting outcomes and treatment response in psychiatry: hope or hype?

Over the last years, the decreased costs and enhanced accessibility to large genome-wide association studies datasets have laid the foundations for the development of polygenic risk scores (PRSs). A PRS is calculated on the weighted sum of single nucleotide polymorphisms and measures the individual genetic predisposition to develop a certain phenotype. An increasing number of studies have attempted to utilize the PRSs for risk stratification and prognostic evaluation. The present narrative review aims to discuss the potential clinical utility of PRSs in predicting outcomes and treatment response in psychiatry. After summarizing the evidence on major mental disorders, we have discussed the advantages and limitations of currently available PRSs. Although PRSs represent stable trait features with a normal distribution in the general population and can be relatively easily calculated in terms of time and costs, their real-world applicability is reduced by several limitations, such as low predictive power and lack of population diversity. Even with the rapid expansion of the psychiatric genetic knowledge base, pure genetic prediction in clinical psychiatry appears to be out of reach in the near future. Therefore, combining genomic and exposomic vulnerabilities for mental disorders with a detailed clinical characterization is needed to personalize care.

Treatment persistence with aripiprazole once monthly: a 4-year follow-up.

OBJECTIVES: Treatment persistence refers to the act of continuing a treatment as prescribed and reflects the patient's or doctor's judgment about efficacy, tolerability, and acceptability. In patients with schizophrenia, antipsychotic persistence is often poor, because of issues such as lack or loss of efficacy, side effects, and poor adherence, which is often related to the degree to which patients find the medication and overall intervention to be helpful, tolerable, fair, reasonable, appropriate, and consistent with expectations of treatment. Despite the poor antipsychotic persistence that has been reported to date in patients with schizophrenia, we previously observed a relatively high (86%) 6 months persistence with aripiprazole once-monthly (AOM) in a group of patients with schizophrenia, treated in the real world Italian clinical practice. The present study explores the longer term persistence with AOM, over a mean follow-up period of 48 months. METHODS: This was a multicenter, retrospective, non-interventional follow-up study, aimed at evaluating the longer term persistence with AOM in a group of patients with schizophrenia who had already shown persistence over a period of at least 6 months. The study included 161 individuals who had participated in our previous study, where 86% of participating individuals had shown persistence with AOM for at least 6 months. Non-persistence was defined as discontinuing the medication for any reason. Baseline demographic and clinical characteristics of patients who continued AOM were then compared to those of patients who discontinued the medication. RESULTS: Study subjects were predominantly male (64.4%) and their mean age was 39.7 (SD: 12.24). Treatment persistence with AOM was 69.6% and 112 out of 161 patients were still receiving AOM treatment at the last follow-up visit. The mean duration of AOM treatment until the last recorded observation was 55.87 months (median 56.17, SD6.23) for the 112 persistent patients and 32.23 (median 28.68.SD 15.09) months for the 49 non-persistent individuals. The mean observation period for all patients (persistent and non-persistent) was 48.78 months (median 52.54, SD 14.64). For non-persistent subjects, the observation period ended with the discontinuation of AOM. Subjects treated with AOM at 400 mg presented a 69.6% lower risk of all-cause treatment discontinuation when compared with patients treated with 300 mg (HR: 0.314; 95% confidence interval [CI] 0.162-0.608; P = 0.001). The main reasons for discontinuation were lack of efficacy (30.6%), patient/caregiver choice (18.4%), physician's choice (16.3%), non-adherence (12.2%) and inconvenience (6.1%). Only 3 patients (6.1%) discontinued AOM for tolerability issues. CONCLUSIONS: In subjects with schizophrenia, who had already shown a 6 months persistence with AOM, a high number of patients (69.6%) continued to be persistent over a 4-year follow-up period. This may reflect a favourable profile of efficacy, tolerability, and acceptability. Larger and prospective studies are warranted to confirm our observations.

Psychological well-being and family distress of Italian caregivers during the COVID-19 outbreak.

The present study aimed to investigate the personal well-being and family distress of Italian caregivers during the lockdown. Five hundred sixty-five family caregivers and 638 age- and sex-matched noncaregivers completed a web-based survey. The following scales were administered to all participants: General Health Questionnaire-12 items (GHQ-12), Insomnia Severity Index (ISI), Brief Resilient Coping Scale (BRCS), and Family Distress Index (FDI). Caregivers were also asked to provide information about their family members with disabilities. Individual and family distress, as well as insomnia, were significantly higher in caregivers than controls. Contrariwise, caregivers reported lower resilience levels. Multiple linear regression showed that distress was higher in caregivers living in Central and Southern Italy. Individual well-being was negatively predicted by low independence measured by the activities of daily living (ADL). Family distress was higher in households of psychiatric patients. Finally, low resilience levels appeared as the strongest predictors of both individual and family distress. The lockdown caused severe distress among caregivers and families of people with disabilities. Support networks for people with disabilities and their families are fundamental to prevent severe consequences from a psychological, social, and economical point of view.

Autism spectrum in patients with schizophrenia: correlations with real-life functioning, resilience, and coping styles.

BACKGROUND: Previous researches highlighted among patients with schizophrenia spectrum disorders (SSD) a significant presence of autistic traits, which seem to influence clinical and functional outcomes. The aim of this study was to further deepen the investigation, evaluating how patients with SSD with or without autistic traits may differ with respect to levels of functioning, self-esteem, resilience, and coping profiles. METHODS: As part of the add-on autism spectrum study of the Italian Network for Research on Psychoses, 164 outpatients with schizophrenia (SCZ) were recruited at eight Italian University psychiatric clinics. Subjects were grouped depending on the presence of significant autistic traits according to the Adult Autism Subthreshold Spectrum (AdAS Spectrum) instrument ("AT group" vs "No AT group"). Other instruments employed were: Autism Spectrum Quotient (AQ), Specific Levels of Functioning (SLOF), Self-Esteem Rating scale (SERS), Resilience Scale for Adults (RSA), and brief-COPE. RESULTS: The "AT group" reported significantly higher scores than the "No AT group" on SLOF activities of community living but significantly lower scores on work skills subscale. The same group scored significantly lower also on SERS total score and RSA perception of the self subscale. Higher scores were reported on COPE self-blame, use of emotional support and humor domains in the AT group. Several correlations were found between specific dimensions of the instruments. CONCLUSION: Our findings suggest the presence of specific patterns of functioning, resilience, and coping abilities among SSD patients with autistic traits.

The safety of agomelatine in standard medical practice in depressed patients: A 26-week international multicentre cohort study.

OBJECTIVE: The present observational cohort study documented the safety of agomelatine in current medical practice in out-patients suffering from major depressive disorder. METHOD: The 6-month evolution of agomelatine-treated patients was assessed with a focus on safety (emergent adverse events, liver acceptability), severity of depression using the Clinical Global Impression Severity (CGI-S) score, and functioning measured by the Sheehan Disability Scale (SDS). RESULTS: A total of 8453 depressed patients from 761 centres in 6 countries were analysed (female: 67.7%; mean age: 49.1 ± 14.8 years). Adverse events reported were in accordance with the known safety profile of agomelatine. Cutaneous events were reported in 1.7% of the patients and increased hepatic transaminases values were reported in 0.9 % of the patients. The incidence of events related to suicide/self-injury was 1.0%. Two completed suicides, not related to the study drug, were reported. CGI-S total scores and SDS sub-scores improved and numbers of days lost or underproductive decreased over the treatment period. CONCLUSIONS: In standard medical practice, agomelatine treatment was associated with a low incidence of side effects. No unexpected events were reported. A decrease in the severity of the depressive episode and improved functioning were observed. TRIAL REGISTRATION NAME: Observational cohort study to evaluate the safety of agomelatine in standard medical practice in depressed patients. A prospective, observational (non-interventional), international, multicentre cohort study. TRIAL REGISTRATION NUMBER: ISRCTN53570733.

Lifetime prevalence of suicidal ideation and suicidal behaviors in gender non-conforming youths: a meta-analysis.

Gender identity represents a topic of growing interest in mental health research. People with non-conforming gender identity are prone to suffer from stigmatization and bullying and often present psychiatric issues, which may in turn lead to a high prevalence of suicidal ideation and behaviors. The present meta-analysis aimed to estimate the prevalence of suicidal ideation and suicidal behaviors in gender non-conforming children, adolescents and young adults. A systematic search was performed in Web of Science and PsycINFO from inception to December 2018. We selected cross-sectional and cohort studies including youths (up to 25 years) with a diagnosis confirmed by a clinician according to international classifications, or after a direct interview with a peer. A random-effects meta-analysis was computed for the following outcomes: non-suicidal self-injury (NSSI), suicidal ideation and suicide attempts. Overall, we found a mean prevalence of NSSI of 28.2% (9 studies, 3057 participants, 95% CI 14.8-47.1). A similar prevalence (28%) was found for suicidal ideation (6 studies, 2249 participants, 95% CI 15-46.3), while the prevalence of suicide attempts was 14.8% (5 studies, 1039 participants, 95% CI 7.8-26.3). Subgroup analyses revealed no significant differences according to biological sex. Given the prevalence of suicidal behaviors in gender non-conforming youths, it appears desirable to implement therapeutic and support strategies for this population. Moreover, educational interventions directed to parents, teachers, mental health professionals and general community should be promoted to struggle against stigma and social isolation, factors that may contribute to increasing the risk of suicidal behaviors.

A new approach for seasonal pattern: is it related to bipolarity dimension? Findings from an Italian multicenter study.

OBJECTIVE: The aims of this study were to assess the impact of seasonal pattern on several clinical dimensions in inpatients with a current major depressive episode and to evaluate clinical differences between unipolar and bipolar depression according to seasonal pattern. METHODS: Study participants were 300 patients affected by major depressive disorder (MDD) or bipolar disorder (BD) currently experiencing a major depressive episode (MDE) and were recruited at three University Medical Centres in Italy. All study subjects completed several evaluation scales for depressive and hypomanic symptoms, quality of life and functioning, impulsiveness, and seasonal pattern. RESULTS: Several differences between BD with and without seasonal pattern, MDD with and without seasonal pattern but in particular between BD and MDD with seasonal pattern were found. Patients with MDE with seasonal pattern had more frequently received a longitudinal diagnosis of BD. CONCLUSIONS: A large number of patients with BD and seasonal pattern, but also a considerable number of patients with MDD and seasonal pattern, endorsed manic items during a current MDE. Seasonal pattern should be associated with a concept of bipolarity in mood disorders and not only related to bipolar disorder. A correct identification of seasonal patterns may lead to the implementation of personalised pharmacological treatment approaches.KEY POINTSHigh prevalence of mixed features in mood disorders with seasonal pattern, supporting the need for a dimensional approach to major depressive disorder and bipolar disorder.Significant percentage of patients with a primary diagnosis of major depressive disorder had seasonal pattern.Significant percentage of patients with a primary diagnosis of major depressive disorder reported (hypo)manic symptomatology.

Mood spectrum symptoms during a major depressive episode: Differences between 145 patients with bipolar disorder and 155 patients with major depressive disorder. Arguments for a dimensional approach.

BACKGROUND: Several studies have challenged the traditional unipolar-bipolar dichotomy in favor of a more dimensional approach. OBJECTIVE: To evaluate the differences in mood spectrum between patients with bipolar disorder (BD) and major depressive disorder (MDD) during a major depressive episode (MDE). METHOD: Study participants were 145 patients with BD and 155 patients with MDD recruited at three University Medical Centers in Italy. All study subjects met Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria for MDE and completed the Mood Spectrum-Self-Report-Last Month questionnaire. RESULTS: Patients with BD endorsed more items in the mood manic/hypomanic and energy depressive subdomains of the MOODS-SR questionnaire. Significant differences were also found for specific depressive and manic items, which were more frequently endorsed by patients with BD. A large number of patients with BD, but also a considerable number of patients with MDD, endorsed manic items during a depressive episode. CONCLUSIONS: There are differences between BD and MDD in terms of the number and type of mood spectrum items that are endorsed during a MDE, which may help to identify patients with BD when a retrospective assessment of a history of mania or hypomania is not possible or not reliable. A high number of patients with BD and a considerable number of patients with MDD endorsed several items in the manic section of the mood, energy, and cognition domains, this confirming the centrality of mixed features in patients with mood disorders and the need for a unitary, dimensional, descriptive and dynamic approach to MDD and BD, such as the recently proposed ACE (Activity, Cognition, Energy) model.

Curcumin for depression: a meta-analysis.

Curcumin is the principal curcuminoid found in turmeric (Curcuma longa), a spice frequently used in Asian countries. Given its anti-inflammatory and antioxidant properties, it has been hypothesized that curcumin might be effective in treating symptoms of a variety of neuropsychiatric disorders, such as depression. We conducted a systematic review following the PRISMA guidelines. In August 2019, we screened 930 articles, of which 9 were eligible for the meta-analysis. In 7 articles, participants were affected by major depressive disorder (MDD), while in other two they suffered from depression secondary to a medical condition. We found an overall significant effect of curcumin on depressive (10 studies, 531 participants, Hedge's g = -0.75, 95% CI -1.11 to -0.39, p < 0.001) and anxiety symptoms (5 studies, 284 participants, Hedge's g = -2.62, 95% CI -4.06 to -1.17, p < 0.001), with large effect size. Curcumin was generally well-tolerated by patients. Our findings suggest that curcumin, if added to standard care, might improve depressive and anxiety symptoms in people with depression. However, given the small sample size, our results should be cautiously interpreted. Further trials should be implemented, particularly in Western countries, where curcumin does not represent a usual component of dietary regimens.