Facts and myths about use of esketamine for treatment-resistant depression: a narrative clinical review.

Introduction and aims: Treatment-resistant depression (TRD) occurs when at least two different antidepressants, taken at the right dosage, for adequate period of time and with continuity, fail to give positive clinical effects. Esketamine, the S-enantiomer of ketamine, was recently approved for TRD treatment from U.S. Food and Drug Administration and European Medicine Agency. Despite proved clinical efficacy, many misconceptions by clinicians and patients accompany this medication. We aimed to review the most common "false myths" regarding TRD and esketemine, counterarguing with evidence-based facts. Methods: The keywords "esketamine", "treatment resistance depression", "depression", "myth", "mythology", "pharmacological treatment", and "misunderstanding" were entered in the main databases and combined through Boolean operators. Results: Misconceptions regarding the TRD prevalence, clinical features and predictors have been found. With respect of esketamine, criteria to start treatment, dissociative symptoms, potential addiction and aspects of administration and monitoring, were found to be affected by false beliefs by clinicians and patients. Discussion and conclusion: TRD represents a challenging condition, requiring precise diagnosis in order to achieve patient's full recovery. Esketamine has been proved as an effective medication to treat TRD, although it requires precautions. Evidence can inform clinical practice, in order to offer this innovative treatment to all patients with TRD.

Combination of Two Long-Acting Antipsychotics in Schizophrenia Spectrum Disorders: A Systematic Review.

BACKGROUND: Up to 34% of patients with schizophrenia are resistant to several treatment trials. Lack of continuous and adequate treatment is associated with relapse, rehospitalization, a lower effect of antipsychotic therapy, and higher risk of side effects. Long-acting injectables antipsychotics (LAI APs) enhance compliance and improve clinical outcomes and quality of life in patients with schizophrenia, and thus it may be advisable to administer two LAI APs at the same time in cases of treatment-resistant schizophrenia. The purpose of this review is to summarize the available literature regarding the combined use of two LAI APs in patients with schizophrenia or other psychotic spectrum disorders. METHODS: An extensive literature search for relevant articles regarding any combination of two long-acting injectable antipsychotics has been performed from inception up to 9 February 2024, on PubMed, Scopus and APA PsycInfo, according to the PRISMA statement. Only studies reporting combination of two LAI APs and its clinical outcome in patients with schizophrenia and related disorders were selected. RESULTS: After the selection process, nine case reports, four case series and two observational retrospective studies were included in the final analysis. All patients treated with dual LAI APs reported a good response, and no new or unexpected adverse effects due to the combination of two LAIs were reported. Different drug combinations were used, and the most frequent association resulted in aripiprazole monohydrate + paliperidone palmitate once monthly (32 times). CONCLUSIONS: Our review highlights that the treatment regimen with two concurrent LAI APs is already widely used in clinical practice and is recognized as providing a promising, effective, and relatively safe therapeutic strategy for treating the schizophrenia spectrum disorders.

The clinical utility and relevance in clinical practice of DSM-5 specifiers for major depressive disorder: A Delphi expert consensus study.

Major depressive disorder (MDD) is a heterogeneous syndrome, associated with different levels of severity and impairment on the personal functioning for each patient. Classification systems in psychiatry, including ICD-11 and DSM-5, are used by clinicians in order to simplify the complexity of clinical manifestations. In particular, the DSM-5 introduced specifiers, subtypes, severity ratings, and cross-cutting symptom assessments allowing clinicians to better describe the specific clinical features of each patient. However, the use of DSM-5 specifiers for major depressive disorder in ordinary clinical practice is quite heterogeneous. The present study, using a Delphi method, aims to evaluate the consensus of a representative group of expert psychiatrists on a series of statements regarding the clinical utility and relevance of DSM-5 specifiers for major depressive disorder in ordinary clinical practice. Experts reached an almost perfect agreement on statements related to the use and clinical utility of DSM-5 specifiers in ordinary clinical practice. In particular, a complete consensus was found regarding the clinical utility for ordinary clinical practice of using DSM-5 specifiers. The use of specifiers is considered a first step toward a "dimensional" approach to the diagnosis of mental disorders.

Are visual analogue scales valid instruments to measure psychological pain in psychiatric patients?

OBJECTIVE: The Psychological-Physical-Pain Visual Analogue Scale (PPP-VAS) was thought to probably help in identifying patients at risk of suicide. However, no data on its validity to measure psychological pain was available. Our main aim was to investigate the convergent validity of the PPP-VAS using two well-validated scales of psychological pain, the Orbach and Mikulincer Mental Pain scale (OMMP) and the Holden et al. Psychache Scale. METHODS: This multicentre study recruited a total of 1618 adult psychiatric inpatients and outpatients in Italy. Psychological pain was evaluated using the OMMP, Holden et al., and PPP-VAS scales. Psychiatric status, suicidal status, physical pain, depression, and hopelessness were also assessed. RESULTS: A structural equation model (SEM) using the items of psychological pain from the PPP-VAS showed that items loaded significantly on the psychological pain factor and showed good fit. Similarly, a second SEM model using the three scales of psychological pain showed acceptable fit and converged into a psychological pain construct. Correlations between the PPP-VAS and depression, hopelessness, and physical pain showed moderate correlations (r = 0.43 to r = 0.67). Finally, psychological pain evaluated with the PPP-VAS was significantly related with recent suicidal ideation in all patients (OR [95 % CI] = 1.07 [1.05, 1.09]) and recent suicide attempts in moderately to severely depressed patients, OR [95 % CI] = 1.01 [1.02, 1.03]. CONCLUSION: The PPP-VAS showed good psychometric properties in evaluating psychological pain. The characteristics of the PPP-VAS makes this scale a great option for its use in clinical practice to detect patients at risk of suicide.

Type of cycle, temperament and childhood trauma are associated with lithium response in patients with bipolar disorders.

BACKGROUND: Lithium stands as the gold standard in treating bipolar disorders (BD). Despite numerous clinical factors being associated with a favorable response to lithium, comprehensive studies examining the collective influence of clinical variables alongside psychopathological dimensions are lacking. Our study aims to enhance comprehension of lithium response in individuals with BD by integrating clinical variables with psychopathological traits and early adverse events. METHODS: We assessed 201 patients with BD for clinical characteristics, childhood trauma, temperament traits, impulsivity, and aggression. Lithium response was evaluated using the gold standard Alda scale, and predictors of lithium response were estimated through a multivariate model. RESULTS: On the total sample, 61 (30.3%) patients were lithium responders according to the Alda scale. Comparatively, lithium responders, in contrast to non-responders, demonstrated a higher prevalence of the mania-depression-interval (MDI) cycle, a more frequent diagnosis of BD type I, and reported an earlier age of onset. They also exhibited less lifetime substance abuse, emotional, physical, and sexual abuse, while scoring higher on hyperthymic and irritable temperament scales. In multivariate analyses, only the MDI cycle (OR,3.47; 95%CI,1.61-7.50) hyperthymic (OR,1.20; 95%CI,1.02-1.41) and irritable temperament (OR,1.28; 95%CI,1.08-1.52) persisted as significant predictors of a positive response to lithium treatment, while emotional (OR,0.87; 95%CI,0.76-0.98) and physical abuse (OR,0.83; 95%CI,0.70-0.98) were predictors of non-response. CONCLUSIONS: In evaluating lithium response in BD, our study highlights the importance of considering clinical variables alongside temperament and childhood adversities. The assessment of hyperthymic and irritable temperament, emotional and physical abuse together with the type of cycle is of particular importance. Furthermore, our findings underscore the significance of systematically assessing the type of cycle in patients with BD through the use of life charts.

Is There a Burnout Epidemic among Medical Students? Results from a Systematic Review.

Background and Objectives: Medical students represent the ideal target group for promoting mental health and mental wellbeing, being exposed to specific risk factors, such as the content of medical training, the exposure to sickness and death, and a stressful academic routine. Medical students report high levels of cynicism and emotional exhaustion, which represent two of the essential features of burnout syndrome. In this systematic review, studies assessing the levels of burnout among medical students through validated tools worldwide were analyzed. Materials and Methods: A systematic review has been performed in order to identify studies: (1) focusing on samples of medical students; (2) evaluating burnout syndrome using validated tools; (3) providing prevalence data on burnout; and (4) written in English. Results: Out of the 5547 papers initially obtained, 64 were finally included in the analysis. The sample sizes ranged from 51 to 2682 participants. Almost all studies had a cross-sectional design; the Maslach Burnout Inventory and its related versions were the most frequently used assessment tools. The prevalence of burnout, which was stratified based on gender and academic stage, ranged from 5.6 to 88%. Burnout was mostly predicted by thoughts of stopping medical education, negative life events, lack of support, dissatisfaction, and poor motivation. Conclusions: The prevalence of burnout syndrome in medical students is quite heterogeneous, reaching a peak of 88% in some countries. However, several predictors have been identified, including negative life events or poor motivation. These findings highlight the need to develop preventive interventions targeting the future generation of medical doctors, in order to improve their coping strategies and resilience styles.

The Role of Lurasidone in Managing Depressive Symptoms in People with Schizophrenia: A Review.

BACKGROUND: Schizophrenia is a severe mental disorder characterized by positive, negative, affective, and cognitive symptoms. Affective symptoms in patients with schizophrenia have traditionally been overlooked or even neglected because they are not considered as fundamental as positive and negative symptoms in the choice of medication. METHODS: This paper aims to systematically evaluate the efficacy and safety of lurasidone in the treatment of depressive symptoms of schizophrenia. RESULTS: Lurasidone appears to be particularly effective on the depressive symptomatology of schizophrenia while also alleviating the positive and negative symptoms associated with the illness. CONCLUSIONS: The efficacy of lurasidone in treating patients with first-episode psychosis who present with predominant depressive symptoms suggests that this medication may be a valuable treatment option not only for established cases of schizophrenia but also for individuals in the early stages of the illness. The good tolerability of lurasidone is an important factor that may positively influence treatment decisions.

Clinician treatment choices for post-traumatic stress disorder: ambassadors survey of psychiatrists in 39 European countries.

BACKGROUND: Considering the recently growing number of potentially traumatic events in Europe, the European Psychiatric Association undertook a study to investigate clinicians' treatment choices for post-traumatic stress disorder (PTSD). METHODS: The case-based analysis included 611 participants, who correctly classified the vignette as a case of PTSD, from Central/ Eastern Europe (CEE) (n = 279), Southern Europe (SE) (n = 92), Northern Europe (NE) (n = 92), and Western Europe (WE) (N = 148). RESULTS: About 82% woulduse antidepressants (sertraline being the most preferred one). Benzodiazepines and antipsychotics were significantly more frequently recommended by participants from CEE (33 and 4%, respectively), compared to participants from NE (11 and 0%) and SE (9% and 3%). About 52% of clinicians recommended trauma-focused cognitive behavior therapy and 35% psychoeducation, irrespective of their origin. In the latent class analysis, we identified four distinct "profiles" of clinicians. In Class 1 (N = 367), psychiatrists would less often recommend any antidepressants. In Class 2 (N = 51), clinicians would recommend trazodone and prolonged exposure therapy. In Class 3 (N = 65), they propose mirtazapine and eye movement desensitization reprocessing therapy. In Class 4 (N = 128), clinicians propose different types of medications and cognitive processing therapy. About 50.1% of participants in each region stated they do not adhere to recognized treatment guidelines. CONCLUSIONS: Clinicians' decisions for PTSD are broadly similar among European psychiatrists, but regional differences suggest the need for more dialogue and education to harmonize practice across Europe and promote the use of guidelines.

Longitudinal trajectories of anxiety and depression in subjects with different mental disorders after one year in the COVID-19 pandemic.

The aim of this study was to prospectively assess the development and trajectories of anxiety and depressive symptoms among subjects with different mental disorders, during the 3rd wave of the COVID-19 pandemic (T0, March-April 2021) while strict containment measures were applied in Italy, and after 3 months (T1, June-July 2021), with reduced restrictive measures. A sample of 527 subjects, with different DSM-5 diagnoses, was enrolled at nine Italian psychiatric outpatient services. Assessments at T0 and T1 included the Generalized Anxiety Disorder 7-Item (GAD-7) for anxiety symptoms, and the Patient Health Questionnaire-9 (PHQ-9) for depressive symptoms. Differences in anxiety and depressive symptoms rates emerged across different mental disorders and a general improvement at T1 was detected for all of them in both the GAD-7 and PHQ-9 scores, except for Psychosis and Obsessive-Compulsive Disorder (OCD). Patients with Feeding and Eating Disorders (FED) reported statistically significantly higher: GAD-7 scores than those with Bipolar Disorder (BD), at both times, and Anxiety Disorders at baseline; PHQ-9 scores than all other diagnostic categories, at both times. Unemployment, no COVID-19 infection, OCD were predictive variables related to GAD-7 scores at T1, while being unmarried, BD or FED related to PHQ-9 scores at T1. Subjects with mental disorders reported anxiety and depressive symptoms during the third pandemic wave and most of patients showed an improvement over a 3-month follow-up, despite differences emerged among diagnostic categories and for the variables involved. Further studies are needed to deepen knowledge on pandemic impact on patients with mental disorders.

The interplay between mentalization, personality traits and burnout in psychiatry training: Results from a large multicenter controlled study.

BACKGROUND: A better characterization of educational processes during psychiatry training is needed, both to foster personal resilience and occupational proficiency. METHODS: An adequate coverage of medical residents at the national level was reached (41.86% of the total reference population, 29 out of 36 training centers-80.55%). Controls were recruited among residents in other medical specialties. All participants were assessed by questionnaires to evaluate early life experiences, attachment style, personality traits, coping strategies, emotional competencies. A Structural Equation Model (SEM) framework was employed to investigate the interplay between individual factors. RESULTS: A total sample of 936 people was recruited (87.9% response-rate; 645 residents in psychiatry, 291 other medical residents). Psychiatry trainees reported a higher prevalence of adverse childhood experiences (emotional abuse, emotional neglect, physical neglect), greater attachment insecurity (anxious or avoidant) in comparison to other medical trainees. Psychiatry residents also reported higher social support-seeking as a coping strategy, lower problem-orientation, and lower transcendence. Lower neuroticism, higher openness to experience, and higher emotional awareness were also observed in psychiatry trainees. Psychiatry training was associated with a redefinition of conflict management skills as a function of seniority. The SEM model provided support for an interplay between early traumatic experiences, mentalization skills (coping strategies, emotion regulation), interpersonal competencies and occupational distress. CONCLUSIONS: The findings of the present study supported a theoretical model based on mentalization theory for the interactions between personal and relational competencies in psychiatry training, thus providing potential target of remodulation and redefinition of this specific process of education.

Microaggression toward LGBTIQ people and implications for mental health: A systematic review.

BACKGROUND: Research suggests that microaggressions detrimentally impact the mental health of members of marginalized social groups. AIMS: The aim of this systematic review was to assess the exposure to microaggressions and related implications on mental health of Lesbian, Gay, Bisexual, Transgender, Intersex, and Queer (LGBTIQ) people. METHOD: Medline, Scopus, PsycINFO, CINAHL, and EMBASE were searched until January 2023. Studies reporting data on the exposure to microaggressions toward LGBTIQ people were identified. Meta-analyses of rates of exposure to microaggression and of the association between microaggressions and mental health outcomes were based on odds ratio (OR) and standardized mean difference (SMD) with 95% confidence intervals (95% CI), estimated through inverse variance models with random effects. RESULTS: The review process led to the selection of 17 studies, involving a total of 9036 LGBTIQ people, of which 6827 identifying as cisgenders, and 492 as heterosexuals, were included in the quantitative synthesis. Overall, LGBTIQ people showed an increased risk of microaggression (SMD: 0.89; 95% CI [0.28, 1.50]), with Transgender people having the highest risk (OR: 10.0; 95% CI [3.08, 32.4]). Microaggression resulted associated with risk of depression (SMD: 0.21; 95% CI [0.05, 0.37]), anxiety (SMD: 0.29; 95% CI [0.17, 0.40]), suicide attempts (OR: 1.13; 95% CI [1.08, 1.18]), alcohol abuse (OR: 1.32; 95% CI [1.13, 1.54]), but not to suicidal ideation (OR: 1.56; 95% CI [0.64, 3.81]) and cannabis abuse (OR: 1.44; 95% CI [0.82, 2.55]). The quality of the evidence was limited by the small number of studies. CONCLUSIONS: LGBTIQ people are at higher risk of microaggressions compared with their cisgender/heterosexual peers, which may lead to mental health consequences. This evidence may contribute to public awareness of LGBTIQ mental health needs and suggest supportive strategies as well as preventive interventions (e.g., supportive programs and destigmatizing efforts) as parts of tailored health-care planning aimed to reduce psychiatric morbidity in this population.

New trends in personalized treatment of depression.

PURPOSE OF REVIEW: Major depressive disorder (MDD) is a common and burdensome severe mental disorder, which is expected to become the leading cause of disease burden worldwide. Most patients with MDD remain untreated/undertreated. For many decades "a trial and error" approach has been adopted for selecting the best treatment plan for each individual patient, but more recently a personalized treatment approach has been proposed, by taking into account several individual and clinical factors (e.g., clinical stage, comorbidity, duration of illness). Therefore, the aim of this study is to address the most relevant innovations in the personalized treatment plan for patients with MDD. RECENT FINDINGS: In recent years, several pharmacological and nonpharmacological innovations have been introduced in the treatment of patients with MDD. As regards pharmacological treatments, the newly developed drugs have an innovative mechanism of action, targeting the glutamatergic systems. These drugs are highly effective in improving depressive symptoms, with a good level of safety and tolerability. As regards nonpharmacological interventions, innovations include both new strategies targeting different domains (e.g., lifestyle interventions aiming to improve the physical symptoms of depression or virtual reality) and classical interventions provided through innovative mechanisms (e.g., web-based psychotherapies and use of digital approaches). Patients globally report a good level of acceptability of these interventions. SUMMARY: Depression is a heterogeneous, complex and multidimensional disorder, representing one of the leading causes of disability worldwide. The final aim of the management of patients is functional recovery, which can be achieved by using personalized, integrated and recovery-oriented interventions. Several innovative pharmacological and nonpharmacological treatments are now available; interventions should be selected on the basis of the patient's needs and preferences in order to tailor the treatment, according to a shared decision-making approach.

Promoting mental health and preventing mental health problems in child and adolescent refugees and asylum seekers: A systematic review on psychosocial interventions.

BACKGROUND: According to the United Nations Commissioner for Refugees (UNHCR), children and adolescents represent 41% of all forcibly displaced individuals. They have to deal with conflicts, violence, and the many difficulties of flight and resettlement during a critical stage of their emotional, social, cognitive, and physical development. They are more likely to experience mental health problems during migration. Despite the several known risk factors, it is frequently challenging for refugees and asylum seekers to get mental health care. In this paper we review available studies on interventions aimed at promoting mental health and at preventing common mental disorders in immigrant adolescents and children. METHODS: The relevant PubMed, Scopus, PsychINFO and Web of Science databases were searched for papers published until March 21, 2023, using ("immigrants" OR "migration" OR "asylum seekers" OR "refugees") AND ("promotion" OR "prevention") AND ("mental health" OR "mental disorders" OR "psych*") AND ("children" OR "adolescents" OR "young adults") as search string. Fourteen articles qualified for the detailed review. RESULTS AND CONCLUSIONS: The majority of available interventions, although highly heterogeneous in format and content, showed significant improvement in several psychopathological dimensions, including trauma-related symptoms, psychological stress, anxiety, depressive and cognitive symptoms. Available studies on interventions for the prevention of mental disorders and the promotion of mental health in refugees and asylum seekers children and adolescents indicate that provided interventions were associated with a global improvement for participants. Implementation strategies to improve their scalability are highly needed.

Facts and myths about the use of lithium for bipolar disorder in routine clinical practice: an expert consensus paper.

BACKGROUND: Bipolar disorder is one of the most burdensome severe mental disorders, characterized by high levels of personal and social disability. Patients often need an integrated pharmacological and non-pharmacological approach. Lithium is one of the most effective treatments available not only in psychiatry, but in the whole medicine, and its clinical efficacy is superior to that of other mood stabilizers. However, a declining trend on lithium prescriptions has been observed worldwide in the last 20 years, supporting the notion that lithium is a 'forgotten drug' and highlighting that the majority of patients with bipolar disorder are missing out the best available pharmacological option. Based on such premises, a narrative review has been carried out on the most common "misconceptions" and "stereotypes" associated with lithium treatment; we also provide a list of "good reasons" for using lithium in ordinary clinical practice to overcome those false myths. MAIN TEXT: A narrative search of the available literature has been performed entering the following keywords: "bipolar disorder", "lithium", "myth", "mythology", "pharmacological treatment", and "misunderstanding". The most common false myths have been critically revised and the following statements have been proposed: (1) Lithium should represent the first choice for the treatment of patients with bipolar disorder; (2) lithium treatment is effective in different patients' groups suffering from bipolar disorder; (3) Drug-drug interaction risk can be easily managed during lithium treatment; (4) The optimal management of lithium treatment includes periodical laboratory tests; (5) Slow-release lithium formulation has advantages compared to immediate release formulation; (6) Lithium treatment has antisuicidal properties; (7) Lithium can be carefully managed during pregnancy. CONCLUSIONS: In recent years, a discrepancy between evidence-based recommendations and clinical practice in using lithium treatment for patients with bipolar disorder has been highlighted. It is time to disseminate clear and unbiased information on the clinical efficacy, effectiveness, tolerability and easiness to use of lithium treatment in patients with bipolar disorder. It is necessary to reinvigorate the clinical and academic discussion about the efficacy of lithium, to counteract the decreasing prescription trend of one of the most effective drugs available in the whole medicine.

Physical activity influences adherence to pharmacological treatments in patients with severe mental disorders: results from the multicentric, randomized controlled LIFESTYLE trial.

Introduction: Poor adherence to pharmacological treatment is frequent in people with severe mental disorders and it often causes lack of effectiveness of many psychotropic drugs. Thus, efforts should be made to improve adherence to pharmacological treatments in patients with these disorders. Methods: In this paper, based on the LIFESTYLE randomized, controlled multicentric trial, we aim to: 1) assess the level of adherence in a real-world sample of patients with severe mental disorders; 2) evaluate differences in treatment adherence according to patients' socio-demographic and clinical characteristics; 3) evaluate the impact of an innovative psychosocial intervention, on patients' adherence to treatments. The Lifestyle Psychosocial Group Intervention consists of group sessions, focused on different lifestyle behaviours, including healthy diet; physical activity; smoking habits; medication adherence; risky behaviours; and regular circadian rhythms. At end of each session a 20-min moderate physical activity is performed by the whole group. Results: The sample consists of 402 patients, mainly female (57.1%, N = 229), with a mean age of 45.6 years (±11.8). Less than 40% of patients reported a good adherence to pharmacological treatments. Adherence to treatments was not influenced by gender, age, diagnosis and duration of illness. At the end of the intervention, patients receiving the experimental intervention reported a significant improvement in the levels of adherence to treatments (T0: 35.8% vs. T3: 47.6%, p < 0.005). Patients practicing moderate physical activity reported a two-point improvement in the levels of adherence [odds ratio (OR): 1,542; 95% confidence intervals (CI): 1,157-2,055; p < 0.001], even after controlling for several confounding factors. Discussion: The experimental lifestyle intervention, which can be easily implemented in the routine clinical practice of mental health centres, was effective in improving adherence to pharmacological treatments.

Psychosocial interventions for carers of people with severe mental and substance use disorders: a systematic review and meta-analysis.

BACKGROUND: Severe mental disorders - such as schizophrenia, bipolar disorder, and substance use disorders - exert a negative impact not only on affected people but also on their carers. To support carers of people with severe mental disorders, several psychosocial interventions have been developed. METHODS: This systematic review and meta-analysis aimed to assess whether psychosocial interventions for carers of persons with schizophrenia, bipolar disorder, or substance use disorders produce benefit/harm with respect to a series of outcomes - including subjective and objective burden, depressive symptoms, well-being/quality of life, sleep, skills/knowledge, self-efficacy, physical health - as compared to standard support/support as usual or other control conditions. RESULTS: In carers of persons with schizophrenia, psychoeducational interventions were associated with significant improvement in personal burden, well-being, and knowledge about the illness; and a supportive-educational intervention with an improvement in personal burden. In carers of persons with bipolar disorder, psychoeducational interventions were associated with significant improvement in personal burden and depressive symptoms; family-led supportive interventions with an improvement in family burden; family-focused intervention and online "mi.spot" intervention with a significant reduction in depressive symptoms. Psychosocial interventions used for carers of persons with substance use disorders were found to be overall effective on the level of well-being, but the low number of trials did not allow detection of differences between the various psychosocial interventions. CONCLUSIONS: The quality of the evidence ranged from very low to moderate, suggesting the need for further better-quality research.

Acute stress symptoms in general population during the first wave of COVID lockdown in Italy: Results from the COMET trial.

BACKGROUND: The coronavirus disease of 2019 (COVID-19) pandemic is an unprecedented traumatic event that has severely impacted social, economic, and health well-being worldwide. The COvid Mental hEalth Trial was specifically designed to evaluate the impact of the COVID-19 pandemic and its containment measures on the mental health of the Italian general population in terms of COVID-19-related acute stress disorder (ASD) symptoms. METHODS: The present cross-sectional study is based on an online survey carried out in the period March-May 2020. Italian general adult population was invited to compile an anonymous survey, which included the severity of acute stress symptoms scale/National Stressful Events Survey Short Scale to investigate the occurrence and severity of ASD symptoms. RESULTS: The final sample consisted of 20,720 participants. During the lockdown, subjects with pre-existing mental health problems reported a statistically significant higher risk of acute post-traumatic symptoms compared to the general population (B: 2.57; 95% CI:2.04-3.09; p < .0001) and health care professionals (B: .37; 95% CI: .02-0.72; p < .05). According to multivariate regression models, the levels of acute post-traumatic symptoms (p < .0001) were higher in younger and female respondents. Social isolation and sleep disorder/insomnia represented positive predictors of acute stress (B = 3.32, 95% CI = 3.08-3.57). CONCLUSIONS: Concerns about the risk of infection as well as social isolation caused a higher incidence of acute post-traumatic stress symptoms that may predict the subsequent development of post-traumatic stress disorder symptoms in the long term.

The predictive role of proinflammatory and neuroendocrine factors in the acute phases of bipolar disorder: study protocol of a longitudinal controlled trial.

INTRODUCTION AND AIMS: Bipolar disorder (BD) is a severe and recurring mental illness associated with a significant personal and social burden. It has been recently hypothesized that increased levels of pro-inflammatory cytokines and cortisol, which is also associated with a reduced expression of the brain-derived neurotrophic factor (BDNF), may influence affective recurrences in BD. Our study aims to: 1) assess changes in the levels of peripheral cytokines, BDNF and salivary cortisol during acute and euthymic phases of bipolar disorder, compared to that of a sample oh healthy controls; 2) evaluate whether these changes represent a biosignature for the different phases of the illness. MATERIALS AND METHODS: Patients aged 18-65 years old, with a diagnosis of BD I or II types, will be enrolled during an acute episode, according to DSM-5 criteria, together with age- and gender-matched healthy controls. Blood and salivary samples will be collected at baseline and after 3 and 6 months. Validated assessment instruments will be administered to all participants for the evaluation of symptom severity, global functioning, suicidal risk, stress levels and physical comorbidities. EXPECTED RESULTS: We expect changes in inflammatory and neuroendocrine indices to be predictive of the onset of an acute phase of bipolar disorder and that overall levels of cytokines, cortisol and BDNF are overall significantly different between BD patients and healthy controls. CONCLUSIONS: The longitudinal design of the study will allow to assess whether the presence of acute affective symptoms in BD patients correlates with significantly higher levels of cytokines and salivary cortisol and with reduced BDNF levels compared to euthymic phases. Moreover, the comparison with healthy control subjects will allow to understand if inflammatory mediators as well as the hypothalamic-pituitary-adrenal (HPA) axis are chronically elevated in BD patients and are independent from mood swings.