Search

Objective: Treatment-resistant depression (TRD) affects around 20-30% of people with major depressive disorder. In 2019, esketamine nasal spray was approved for TRD by both the US Food and Drug Administration and the European Medicines Agency. While its clinical efficacy and safety are proven, the mechanisms underlying its antidepressant effect remain unclear. The use of metabolomics may allow understanding the metabolic effects of esketamine and predicting biological features associated with clinical response in TRD. Nonetheless, there is a lack of studies exploring the predictive value of metabolomics. The Resistant Depression Response to Esketamine Assessing Metabolomics (ReDREAM) project aims at identifying metabolic biosignatures that may represent novel correlates of response to esketamine treatment., Study Design: This is the protocol of an observational, prospective study., Methods: We plan to select 60 people with TRD from 3 clinical sites in Italy. The participants will be administered with esketamine nasal spray, following standard clinical practice, twice a week for 4 weeks ("induction phase"), then once a week for 4 additional weeks ("maintenance phase"). We will test the correlations between baseline metabolic profile and depressive symptom improvement at study endpoints (weeks 4 and 8) and we will explore the likelihood of different metabolic phenotypes between responders and non-responders., Expected Results: An involvement of energy metabolism, amino acid metabolism, urea cycle, and nitric oxide synthesis in response to treatment with esketamine nasal spray is hypothesized., Conclusion: Unbiased data from untargeted metabolomics associated with clinical changes after esketamine treatment may contribute to define new paradigms for precision psychiatry-oriented, personalized care of TRD., Competing Interests: Declaration of Interests: Francesco Bartoli is Editor-in-Chief of Alpha Psychiatry and was not involved in the processing of this article. In the last three years, he has received consultant fees by IQVIA Solutions Italy and Edra S.p.A., and carried out paid editorial activities for Elsevier and AVES. In the last three years Renato de Filippis has received speaker fee from Janssen, Angelini, Lundbeck, and Rovi, and travel support from Rovi, Otsuka, Lundbeck, and Janssen. In the last three years Umberto Albert received speaker fee from Angelini Pharma, Janssen Pharmaceutica, OM Pharma Suisse, Lundbeck, Fidia, and Boehringer. The other authors declare no conflicts of interest., (2024 authors.)

Binge eating disorder (BED) is the most prevalent form of disordered eating, frequently associated with obesity. Both these conditions along with sharing overeating behaviour features can lead to substantial burden of disease and premature mortality. With limited specific evidence available on pharmacotherapy, since lisdexamfetamine is approved only in some countries, new drugs are urgently needed to provide physicians with efficacious prescribing choices when treating BED. Although unique mechanisms underlie psychopathological features of binge eating, including impulsivity, compulsivity, and emotional reactivity, anti-obesity drugs might represent an option for both weight management and symptom reduction in people with BED. The aim of this review is thus to provide a summary of available evidence on the efficacy of anti-obesity drugs for BED. After comprehensively searching for relevant studies in PubMed and the Cochrane Library, as well as for unpublished results in ClinicalTrials.gov, we included 14 clinical trials. Despite the limited sample size and the methodological variability, evidence from available studies suggests that most anti-obesity drugs, namely phentermine/topiramate, naltrexone/bupropion, liraglutide and semaglutide, though not orlistat, might variously achieve improvements for both body weight and severity and frequency of binge episodes. Findings from ongoing clinical trials are likely to provide further insight into the possible role of anti-obesity drugs for treating BED. Since these agents can hold the potential to be misused potentiating dietary restriction and pathological weight loss, it is crucial to promote responsible prescribing practices., Competing Interests: Declaration of Interests: The authors have no conflicts of interest to declare., (2024 authors.)

The antidepressant effects of ketamine and esketamine are well-documented. Nonetheless, most of the underlying molecular mechanisms have to be uncovered yet. In the last decade, metabolomics has emerged as a useful means to investigate the metabolic phenotype associated with depression as well as changes induced by antidepressant treatments. This mini-review aims at summarizing the main findings from preclinical and clinical studies that used metabolomics to investigate the metabolic effects of subanesthetic, antidepressant doses of ketamine and esketamine and their relationship with clinical response. Both animal and human studies report alterations in several metabolic pathways - including the tricarboxylic acid cycle, glycolysis, the pentose phosphate pathway, lipid metabolism, amino acid metabolism, the kynurenine pathway, and the urea cycle - following the administration of ketamine or its enantiomers. Although more research is needed to clarify commonalities and differences in molecular mechanisms of action between the racemic compound and its enantiomers, these findings comprehensively support an influence of ketamine and esketamine on mitochondrial and cellular energy production, membrane homeostasis, neurotransmission, and signaling. Metabolomics may thus represent a promising strategy to clarify molecular mechanisms underlying treatment-resistant depression and related markers of clinical response to ketamine and esketamine. This body of preclinical and clinical evidence, if further substantiated, has the potential to guide clinicians towards personalized approaches, contributing to new paradigms in the clinical management of depression., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Organisational and individual barriers often prevent university students from seeking mental health support. Digital technologies are recognised as effective in managing psychological distress and as a source of health-related information, thus representing useful options to address mental health needs in terms of accessibility and cost-effectiveness. However, university students' experiences and perspectives towards such interventions are little known., Objectives: We thus aimed to expand the existing base of scientific knowledge, focusing on this special population., Methods: Data were from the qualitative component of "the CAMPUS study", longitudinally assessing the mental health of students at the University of Milano-Bicocca (Italy) and the University of Surrey (UK). We conducted in-depth interviews and thematically analysed the transcripts using the framework approach., Results: An explanatory model was derived from five themes identified across 33 interviews (15 for Italy, 18 for the UK). Students perceived that social media, apps, and podcasts could deliver relevant mental health content, ranging from primary to tertiary prevention. Wide availability and anonymity were perceived as advantages that make tools suitable for preventive interventions, to reduce mental health stigma, and as an extension of standard treatment. These goals can be hindered by disadvantages, namely lower efficacy compared to face-to-face contact, lack of personalisation, and problematic engagement. Individual and cultural specificities might influence awareness and perspectives on the use of digital technologies for mental health support., Conclusion: Although considering some specific features, digital tools could be a useful instrument to support the mental health needs of students. Since personal contact remains crucial, digital tools should be integrated with face-to-face interventions through a multi-modal approach., Competing Interests: Prof. Giuseppe Carrà is the Editorial Advisory Board Member for the journal Clinical Practice & Epidemiology in Mental Health., (© 2024 The Author(s). Published by Bentham Open.)

Long-acting injectable (LAI) antipsychotics are often used for the long-term management also of bipolar disorder (BD). Nonetheless, evidence on their effect on pragmatic outcomes such as hospitalization risk in BD is inconsistent. We carried out a mirror-image study comparing rates and number of days of hospitalization, one year before and after the initiation of LAI treatment, in a sample of subjects with BD. Participants were selected from the STAR Network Depot Study, a pragmatic, observational, multicenter research involving a cohort of inpatients and outpatients consecutively started on LAI treatment. Variations in rates and in total number of days of hospitalization between the 12 months before and those after treatment initiation were analyzed. Among 461 individuals screened for eligibility, we included 71 adults with BD, initiated either on first- (FGA) or second-generation (SGA) LAIs. We found a significant decrease in terms of 12-month hospitalization rates (p < 0.001) and number of days (p < 0.001) after LAI initiation, without any effect by age, gender, alcohol/substance use disorders, and symptom severity. Subgroup analyses based on antipsychotic class, history of LAI treatment, and concomitant oral medications, confirmed the decreasing trend on both hospitalization rates and number of days. However, these reductions were not significant among participants who continued this treatment for less than 6 months. Comprehensively, this study supports the role of LAIs as effective maintenance treatment options for BD. Further research is needed to identify clinical characteristics of people with BD who would most benefit from long-acting formulations of antipsychotics., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Clinical trials and real-world data have shown that long-acting injectable antipsychotics (LAIs) might be an effective therapeutic option also for people with bipolar disorder (BD). However, complementing evidence from mirror-image studies investigating LAIs in BD is scattered and has not been systematically evaluated so far. We thus performed a review of observational mirror-image studies testing the effectiveness of LAI treatment on clinical outcomes in people with BD. Embase, MEDLINE, and PsycInfo electronic databases were systematically searched (via Ovid) up to November 2022. We included six mirror-image studies that compared relevant clinical outcomes between the 12-months after (post-treatment period) and the 12-months before (pre-treatment period) the initiation of a LAI treatment in adults with BD. We found that LAI treatment is associated with a significant reduction in days spent in hospital and number of hospitalizations. Moreover, LAI treatment seems to be associated with a significant decrease in the proportion of individuals with at least one hospital admission, even though data on this outcome were reported by just two studies. In addition, studies consistently estimated a significant reduction of hypo-/manic relapses after LAI treatment initiation, while the effect of LAIs for depressive episodes is less clear. Finally, LAI treatment initiation was associated with a lower number of emergency department visits in the year after LAI initiation. The findings of this review seem to suggest that the use of LAIs is an effective strategy to improve major clinical outcomes in people with BD. Nonetheless, additional research, based on standardized assessments of prevalent polarity and relapses, is needed to identify the clinical characteristics of individuals with BD who are most likely to benefit from a LAI treatment., Competing Interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: SP reports grants and honoraria outside the submitted work. Other authors declare that there is no conflict of interest., (© The Author(s), 2023.)

Introduction: COVID-19 restrictions introduced several changes in university academic and social experience. Self-isolation and online teaching have amplified students' mental health vulnerability. Thus, we aimed to explore feelings and perspectives about the impact of the pandemic on mental health, comparing students from Italy and the UK., Methods: Data were collected from the qualitative portion of "the CAMPUS study", longitudinally assessing mental health of students at the University of Milano-Bicocca (Italy) and the University of Surrey (UK). We conducted in-depth interviews and thematically analysed the transcripts., Results: The explanatory model was developed from four themes identified across 33 interviews: anxiety exacerbated by COVID-19; putative mechanisms leading to poor mental health; the most vulnerable subgroups; and coping strategies. Generalised and social anxiety resulted from COVID-19 restrictions by being associated with loneliness, excessive time online, unhealthy management of time and space and poor communication with the university. Freshers, international students, and people on the extremes of the introversion/extroversion spectrum, were identified as vulnerable, while effective coping strategies included taking advantage of free time, connection with family and mental health support. The impact of COVID-19 was mostly related to academic issues by students from Italy, whereas to the drastic loss of social connectedness by the UK sample., Conclusions: Mental health support for students has an essential role, and measures that encourage communication and social connectedness are likely to be beneficial.

Many European countries have seen increasing refugee populations and asylum applications over the past decade. Forcibly displaced persons (FDPs) are known to be at higher risk of developing mental disorders and are in need of specific care. Thus, specific training for mental health professionals is recommended by international health organizations. The aim of this exploratory study was to assess the experience of clinical work with FDPs among psychiatric trainees in Europe and Central Asia as well as their interest and specific training received on this topic. An online questionnaire was designed by the Psychiatry Across Borders working group of the European Federation of Psychiatric Trainees (EFPT) and was distributed via email through local networks among European trainees from 47 countries between March 2017 and April 2019. Answers of 342 psychiatric trainees from 15 countries were included in the survey analysis. A majority of trainees (71%) had had contact with FDPs in the last year of their clinical work. Although three-quarters expressed a strong interest in the mental health of FDPs, only 35% felt confident in assessing and treating them. Specific training was provided to 25% of trainees; of this subset, only a quarter felt this training prepared them adequately. Skills training on transcultural competencies, post-traumatic stress disorder, and trauma management was regarded as essential to caring for refugees with confidence. Although psychiatric trainees are motivated to improve their skills in treating FDPs, a lack of adequate specific training has been identified. The development of practical skills training is essential. International online training courses could help meet this pressing need.

Introduction: Pteridines, such as neopterin, biopterin, and tetrahydrobiopterin (BH 4 ), may be involved in depression pathophysiology owing to their links to immune-inflammatory response, oxidative and nitrosative stress, and monoaminergic transmission. Nonetheless, studies assessing pteridines in depression are inconsistent. We conducted a systematic review and meta-analysis of observational studies comparing blood pteridine concentrations between subjects with depression and healthy controls (HCs)., Methods: We searched Embase, MEDLINE, and PsycInfo for articles indexed through November 2021. Study quality was appraised, evaluating age and gender comparability between groups, sample representativeness, and methods to assess depression. Random-effects meta-analyses were carried out, generating pooled standardized mean differences (SMDs). Heterogeneity across studies was estimated using the I 2 statistic., Results: Twenty-four studies, involving 3075 subjects, were included. Individuals with depression showed blood neopterin concentrations higher than HCs (k = 19; SMD = 0.36; p < 0.001) with moderate heterogeneity across studies (I 2  = 58.2%). No moderating role of age, gender, or type of blood sample was found. Sensitivity analyses showed no impact of inconsistency and quality of studies on findings. Neopterin concentrations were higher among individuals with major depressive disorder compared to HCs (SMD = 0.44; p < 0.001). This held true also when considering only drug-free subjects (SMD = 0.68; p = 0.003). No differences in biopterin concentrations were found between subjects with depression and HCs (k = 5; SMD = -0.35; p = 0.086), though this result was limited by inconsistency of findings (I 2  = 77.9%) and quality of studies. Finally, no sufficient data were available for a meta-analysis on BH 4 ., Conclusions: As a whole, our work partly supports the hypothesis of an imbalance of pteridine metabolism in depression., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: Attention deficit hyperactivity disorder is a frequent comorbid condition in adults with bipolar disorder. We performed a meta-analysis aimed at assessing sociodemographic and clinical correlates of attention deficit hyperactivity disorder in bipolar disorder., Method: We searched main electronic databases up to June 2021. Random-effects meta-analyses, with relevant meta-regression and quality-based sensitivity analyses, were carried out to estimate the association between attention deficit hyperactivity disorder and putative correlates, grading the quality of evidence., Results: We included 43 studies, based on 38 independent samples. Attention deficit hyperactivity disorder participants were more likely to be males (odds ratio = 1.46; p  < 0.001) and unemployed (odds ratio = 1.45; p  = 0.045), and less likely to be married (odds ratio = 0.62; p  = 0.014). They had an earlier onset of bipolar disorder (standardized mean difference = -0.36; p  < 0.001); more mood episodes (standardized mean difference = 0.35; p  = 0.007), particularly depressive (standardized mean difference = 0.30; p  = 0.011) and mixed (standardized mean difference = 0.30; p  = 0.031) ones; higher odds of using antidepressants (odds ratio = 1.80; p  = 0.024) and attempted suicides (odds ratio = 1.83; p  < 0.001) and lower odds of psychotic features (odds ratio = 0.63; p  = 0.010). Moreover, they were more likely to have generalized anxiety disorder (odds ratio = 1.50; p  = 0.019), panic disorder (odds ratio = 1.89; p  < 0.001), social phobia (odds ratio = 1.61; p  = 0.017), eating disorders (odds ratio = 1.91; p  = 0.007), antisocial personality disorder (odds ratio = 3.59; p  = 0.004) and substance (odds ratio = 2.29; p  < 0.001) or alcohol (odds ratio = 2.28; p  < 0.001) use disorders. Quality of the evidence was generally low or very low for the majority of correlates, except for bipolar disorder onset and alcohol/substance use disorders (high), and suicide attempts (moderate)., Conclusion: Comorbid bipolar disorder/attention deficit hyperactivity disorder may have some distinctive clinical features including an earlier onset of bipolar disorder and higher comorbid alcohol/substance use disorder rates. Further research is needed to identify additional clinical characteristics of this comorbidity.

University students are particularly vulnerable to mental health issues, with anxiety and depression identified as the most common conditions. During the COVID-19 pandemic, social distancing, self-isolation, and difficulties linked to online teaching and learning have increased their burden of anxiety and depressive symptoms. Thus, the urgent need to intervene in favour of these vulnerable subjects, together with the difficulties in delivering in-person interventions because of lockdowns and restrictions, has led to prioritize digital mental health strategies. This study aimed at systematically reviewing the existing literature on digital mental health interventions targeting anxiety and depressive symptoms in university students during the COVID-19 emergency. Systematic searches of Medline, Embase, and PsycInfo databases identified eight randomized controlled trials. Regarding anxiety symptoms, digitally delivered cognitive behavioural therapy, dialectical behaviour therapy, and mind-body practice techniques emerged as valid strategies, while digital positive psychology and mindfulness-based interventions showed mixed results. On the other hand, digitally delivered dialectical behaviour therapy and positive psychology interventions have shown some efficacy in reducing depressive symptoms. Overall, the available literature, albeit of low quality, seems to support the role of digital interventions in promoting the mental health of university students during the COVID-19 pandemic., (© 2022 SEP y SEPB. Published by Elsevier España, S.L.U. All rights reserved.)

In the last four decades, mental health services for people with Severe Mental Illness (SMI) have seen asylums replaced by a balanced model of Community Mental Healthcare (CMH). Innovative approaches and strategies in the field of CMH have been extensively researched. However, this research has been hampered by issues limiting their capacity to inform clinicians and policymakers. We conducted an overview of meta-analyses of the effectiveness of innovative CMH models focussing on clinical and psychosocial outcomes in comparisons with standard care in adults with SMI. Based on the 12 eligible studies, we appraised, synthesised and graded the resulting evidence. There was moderate quality evidence that case management, Early Intervention Services (EIS) and caregiver-directed interventions were superior to standard care in reducing hospital admission. In relation to psychosocial outcomes, EIS showed high quality evidence of a small effect on global functioning. There was moderate quality evidence for a similar effect of Intensive Case Management, and for a large effect of family intervention. For quality of life, both EIS and self-management education had a small effect, with moderate quality. The level of research about effective CMH models is therefore substantial. However, several gaps related to innovative CMH not yet covered in meta-analytic synthesis, need to be filled.

Attention deficit/hyperactivity disorder (ADHD) is associated with poor academic performance also among university students. This relationship may be made more complex by comorbid conditions. The aim of this study was to evaluate the mediating role of anxiety and depressive symptoms in the relationship between ADHD and academic performance. Data were drawn from the CAMPUS study (registration number: 0058642/21), an ongoing survey on university students’ mental health. Using a logit model, mediation analyses were carried out to test whether the relationship between ADHD symptoms (assessed by ASRS-5) and academic performance might be mediated by depressive (assessed by PHQ-9) and anxiety (assessed by GAD-7) symptoms. Our results showed that worse academic performance is associated with ADHD symptoms (p < 0.001). However, about 24% of the overall association between ADHD symptoms and academic performance was mediated by depressive symptoms (indirect effect: 0.065, 95%CI 0.022; 0.100), whereas the contribution of anxiety symptoms to the model was not significant. Along with the association between ADHD symptoms and poor academic performance, our findings highlight the key mediating role of depressive symptoms, which may be targeted with tailored support, ultimately improving both the academic performance and the well-being of university students with ADHD.

Background: The mental health of the Italian population declined at the onset of the COVID-19 pandemic. However, nationwide population prevalence estimates may not effectively reproduce the heterogeneity in distress responses to the pandemic. In particular, contextual determinants specific to COVID-19 pandemic need to be considered. We thus aimed to explore the association between local COVID-19 mortality rates and mental health response among the general population., Methods: We capitalised on data (N = 17,628) from a large, cross-sectional, national survey, the COMET study, run between March and May 2020. While psychological distress was measured by General Health Questionnaire-12 (GHQ-12), the Depression, Anxiety and Stress Scale-21 Items (DASS-21) was used to assess relevant domains. In addition, a Covid-19 mortality ratio was built to compare single regional mortality rates to the national estimate and official statistics were used to control for other area-level determinants., Results: Adjusted ordered regression analyses showed an association between mortality ratio and moderate (OR = 1.10, 95%CI 1.03-1.18) and severe (OR = 1.11, 95%CI 1.03-1.21) DASS-21 anxiety levels. No effects of mortality ratio on GHQ-12 scores and DASS-21 depression and stress levels, uniformly high across the country, were estimated., Conclusions: Although we could not find any association between regional COVID-19 mortality ratio and depression or psychological distress, anxiety levels were significantly increased among subjects from areas with the highest mortality rates. Local mortality rate seems a meaningful driver for anxiety among the general population. Considering the potentially long-lasting scenario, local public health authorities should provide neighbouring communities with preventive interventions reducing psychological isolation and anxiety levels., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In this prospective study, we assessed the effectiveness and acceptability of paliperidone palmitate 1-month (PP1M) and aripiprazole monohydrate (AM) over 1-year follow-up. We included 195 subjects (117 treated with PP1M and 78 with AM) with schizophrenia spectrum disorders from real-world settings. We estimated no differences in hospitalization (Odds Ratio=1.59; p = 0.12), symptoms improvement (p = 0.90 adjusted for baseline severity), and discontinuation (Hazard Ratio=0.72; p = 0.20) at study endpoint. Although current evidence suggests the possible superiority of AM over PP1M, our findings showed comparable effectiveness between these drugs. Additional studies in real-world settings with direct comparisons between these two LAIs are needed., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The responsiveness of professionals working with children and families is of key importance for child maltreatment early identification. However, this might be undermined when multifaceted circumstances, such as the COVID-19 pandemic, reduce interdisciplinary educational activities. Thanks to technological developments, digital platforms seem promising in dealing with new challenges for professionals' training. We examined a digital approach to child maltreatment training through the ERICA project experience (Stopping Child Maltreatment through Pan-European Multiprofessional Training Programme). ERICA has been piloted during the pandemic in seven European centers involving interconnected sectors of professionals working with children and families. The training consisted of interactive modules embedded in a digital learning framework. Different aspects (technology, interaction, and organization) were evaluated and trainers' feedback on digital features was sought. Technical issues were the main barrier, however, these did not significantly disrupt the training. The trainers perceived reduced interaction between participants, although distinct factors were uncovered as potential favorable mediators. Based on participants' subjective experiences and perspectives, digital learning frameworks for professionals working with children and families (such as the ERICA model nested in its indispensable adaptation to an e-learning mode) can represent a novel interactive approach to empower trainers and trainees to tackle child maltreatment during critical times such as a pandemic, and as an alternative to more traditional learning frameworks.

Attention Deficit-Hyperactivity disorder (ADHD) may influence rates of Alcohol Use Disorder (AUD) among individuals suffering from Bipolar Disorder (BD). The aim of this systematic review and meta-analysis was to estimate the strength and consistency of the potential association between ADHD and AUD in BD. We searched main electronic databases for studies indexed up to November 2020. We included observational studies investigating the association between ADHD and AUD among individuals with BD. The association between ADHD and AUD was estimated using odds ratios (ORs) with 95% Confidence Intervals (CIs). Eleven studies, involving 2734 individuals with BD (516 with ADHD), were included in the meta-analysis. Individuals with both BD and ADHD had higher rates of AUD as compared with subjects with BD only (34.0% vs. 18.3%). The estimated OR of AUD for ADHD was 2.50 (95% CI: 1.91 to 3.27; I 2 = 13.0%). Study-level characteristics did not influence the effect size. No risk of publication bias was estimated. Despite some limitations, this meta-analysis estimated an association between ADHD and AUD among individuals suffering from BD. At least a portion of the high rates of AUD in BD may, thereby, be related to comorbid ADHD. Longitudinal studies are needed to clarify the nature of this relationship.

Several drugs previously tested in clinical trials and approved for different indications have been repurposed for bipolar disorder. We carried out a systematic meta-review of meta-analyses of randomized placebo-controlled trials investigating repurposed drugs as adjunctive treatments for mania and bipolar depression. We performed a critical appraisal using 'A MeaSurement Tool to Assess systematic Reviews' Version 2 (AMSTAR 2). We synthesized results on efficacy, tolerability, and safety, assessing evidence quality according to the 'Grading of Recommendations, Assessment, Development and Evaluations' (GRADE) approach. Our systematic search identified nine eligible studies investigating 12 drugs, four for mania and eight for bipolar depression. The quality of reporting was heterogeneous according to AMSTAR 2. In mania, allopurinol (for symptoms reduction and remission at 4-8 weeks) and tamoxifen (for response and symptoms reduction at 4-6 weeks) showed higher efficacy than placebo, with low and very low quality of evidence, respectively. Concerning bipolar depression, modafinil/armodafinil (for response, remission, and symptoms reduction at 6-8 weeks) and pramipexole (for response and symptoms reduction at 6 weeks) were superior to placebo, despite the low quality of evidence. Results on the efficacy of celecoxib and N-acetylcysteine were of low quality and limited to certain outcomes. Overall, the lack of evidence of high and moderate quality does not allow us to draw firm conclusions on the clinical utility of repurposed drugs as adjunctive treatments for mania and bipolar depression, highlighting the need for additional research., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Although cannabis' major psychoactive component, Δ-9-tetrahydrocannabinol (THC), has been linked to both earlier onset and poorer outcomes of psychotic disorders, Cannabidiol (CBD) seems to have different pharmacological mechanisms and potential therapeutic properties. However, no clinical study has investigated CBD for the treatment of co-occurring psychotic and cannabis use disorders so far, even though its utility seems grounded in a plausible biological basis. The aim of this work is thus to provide an overview of available clinical studies evaluating the efficacy of CBD for psychotic symptoms induced by THC, schizophrenia, and cannabis use disorders. After searching for relevant studies in PubMed, Cochrane Library, and ClinicalTrials.gov, we included 10 clinical studies. Available evidence suggests that CBD may attenuate both psychotic-like symptoms induced by THC in healthy volunteers and positive symptoms in individuals with schizophrenia. In addition, preliminary data on the efficacy of CBD for cannabis use disorders show mixed findings. Evidence from ongoing clinical studies will provide insight into the possible role of CBD for treating psychotic and cannabis use disorders.

Purpose: To explore electroencephalographic (EEG) alterations in young women with different eating disorder (ED) psychopathology levels., Methods: Thirty-seven young women completed general and ED psychopathology (i.e., the ED Examination Questionnaire; EDE-Q) measures. EEG power spectra data were investigated in two conditions: (a) 5 min of resting state (RS) and (b) 5 min of RS after a single taste of a milkshake (ML-RS). EEG analyses were performed using exact Low-Resolution Electromagnetic Tomography software (eLORETA)., Results: Cluster analysis performed on the EDE-Q responses revealed a group of 17 women with high levels of ED pathology falling into the subclinical (i.e., sub-threshold) EDs category and a group of 20 women with low levels of ED pathology (controls). In the RS conditions, no significant modifications were observed between groups. Compared to controls, women with subclinical EDs showed an increase in theta activity in the parieto-occipital areas in the ML-RS condition. After controlling for body mass index and general psychopathology, theta activity in these brain structures was positively associated with EDE-Q global and subscale (restraint, shape and weight concern) scores., Conclusions: Our results may reflect the neurophysiological substrate of ED psychopathology core features like shape/weight concerns. Previous brain imaging and qEEG studies with full-syndrome ED patients also underscored the involvement of parieto-occipital areas in ED pathophysiology. These studies also found brain alterations in the RS condition, not observed here. This is notable given that full-syndrome and subclinical EDs are considered as different manifestations of the same disease along a severity spectrum., Level of Evidence: Level V, cross-sectional, electroencephalographic, descriptive study.

Background and objectives : Readmissions of youths hospitalized for a severe mental disorder are common events and bear a remarkable human, social, and economic burden. The current study aimed at evaluating predictors of 1-year rehospitalization in a sample of adolescents and young adults with severe mental disorders. Materials and Methods : Data for ≤25-year-old inpatients with a severe mental disorder and consecutively admitted between 1 January 2016 and 30 June 2019 were collected. Subjects were retrospectively assessed over a follow-up period of one year after the index discharge to track readmissions-i.e., the primary outcome variable. Standard descriptive statistics were used. The association between variables and 1-year rehospitalization was estimated using the univariate Cox proportional hazards regression model. We then carried out a multivariable Cox regression model, also estimating the covariate-adjusted survivor function. Hazard ratios (HRs) with related 95% confidence intervals (95% CIs) were provided. Results : The final sample included 125 individuals. The multivariable Cox regression model estimated that co-occurring substance use disorders (HR = 2.14; 95% CI: 1.08 to 4.26; p = 0.029) and being admitted for a suicide attempt (HR = 2.49; 95% CI: 1.13 to 5.49; p = 0.024) were both significant predictors of 1-year rehospitalization. Conclusions : Our study showed that comorbid substance use disorders and being admitted for a suicide attempt were predictors of early readmission in youths with severe mental disorders. Although their generalizability is limited, our findings could contribute to improve the quality of young patients' mental health care by identifying vulnerable subjects who may benefit from tailored interventions to prevent rehospitalizations.

Previous research has hypothesized a role for serum uric acid as a marker of mental disorders and related behaviors, possibly due to its link with purinergic transmission and antioxidant activity. We tested the association of serum uric acid levels with specific behavioral and clinical characteristics in 99 individuals suffering from major affective disorders. Subjects were assessed and interviewed using the Kessler Psychological Distress Scale, the Columbia-Suicide Severity Rating Scale, the Modified Overt Aggression Scale, and the Barratt Impulsiveness Scale. We found that psychological distress and suicidal ideation severity were associated with lower uric acid serum levels. On the other hand, verbal aggression and history of violence were associated with higher levels of serum uric acid. However, according to linear regression analyses, there were no behavioral and clinical characteristics independently associated with serum uric acid. Serum uric acid levels were influenced by creatinine and BMI, as well as, possibly, by white blood cells count and gender. Despite some limitations, these results suggest that no behavioral / clinical features are associated with variations of serum uric acid, which rather seem attributable to specific biochemical and metabolic parameters. Nevertheless, the role of purinergic system in different mental disorders and behavioral abnormalities, deserves further research., (Copyright © 2018. Published by Elsevier B.V.)

Background:: Little is known about the influence of contextual characteristics on comorbid substance use and serious mental illness (SMI)., Aims:: To explore the role of poverty on comorbid SMI and cannabis use., Methods:: We used data from the 2015 National Survey on Drug Use and Health, considering those in poverty, with income under 100% of the US poverty threshold., Results:: People in poverty were more likely to suffer from concurrent SMI and cannabis use (3.07%, 95% confidence interval (CI):1.84%; 5.07%), even controlling for gender, age, tobacco and alcohol use (odds ratio (OR) = 2.77, 95% CI: 1.27; 6.03, p = .010)., Conclusion:: The magnitude of the association between SMI and cannabis use is influenced by poverty status. More research on potential mediators like income inequality and impoverished social capital is needed.

Background: Randomised placebo-controlled trials investigating treatments for bipolar disorder have been hampered by wide variations of active drugs and placebo clinical response rates. It is important to estimate whether the active drug or placebo response has a greater influence in determining the relative efficacy of drugs for psychosis (antipsychotics) and relapse prevention (mood stabilisers) for bipolar depression and mania., Methods: We identified 53 randomised, placebo-controlled trials assessing antipsychotic or mood stabiliser monotherapy ('active drugs') for bipolar depression or mania. We carried out random-effects meta-regressions, estimating the influence of active drugs and placebo response rates on treatment relative efficacy., Results: Meta-regressions showed that treatment relative efficacy for bipolar mania was influenced by the magnitude of clinical response to active drugs ( p=0.002), but not to placebo ( p=0.60). On the other hand, treatment relative efficacy for bipolar depression was influenced by response to placebo ( p=0.047), but not to active drugs ( p=0.98)., Conclusions: Despite several limitations, our unexpected findings showed that antipsychotics / mood stabilisers relative efficacy for bipolar depression seems unrelated to active drugs response rates, depending only on clinical response to placebo. Future research should explore strategies to reduce placebo-related issues in randomised, placebo-controlled trials for bipolar depression.

The current systematic review and meta-analysis aimed at exploring acute effects of intravenous (IV) ketamine, an antagonist of N-methyl-D-aspartate (NMDA), in subjects with current suicidal ideation. We included clinical trials testing a single IV dose of ketamine and assessing changes in suicidal ideation within 4h after treatment. Meta-analyses based on random-effects models, were carried out generating pooled standardized mean differences (SMDs) between endpoint and baseline scores. Heterogeneity among studies was estimated using the I 2 index. We searched main Electronic Databases, identifying five studies that met our inclusion criteria. The trials included 99 subjects treated with IV ketamine bolus or infusion. Data showed a large (SMD=-0.92; 95%CI: -1.40 to -0.44; p<0.001) and consistent (I 2 =21.6%) decrease of suicidal ideation, with effects comparable between IV bolus and infusion ketamine. Additional analyses confirmed the efficacy of ketamine across different time points. However, relevant, emerging evidence should be considered as 'very low' so far. Randomized, controlled and adequately powered trials are needed., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objectives: We tested whether serum total cholesterol levels might be associated with recent suicide attempts in subjects with major depressive disorder, after controlling for relevant individual characteristics., Design and Methods: We conducted a comparative cross-sectional study including consecutive inpatients with major depressive disorder. We differentiated subjects admitted for a recent serious (violent or non-violent) suicide attempt and those without such recent history. Total cholesterol was measured from fasting blood tests., Results: At univariate analyses, suicide attempters had levels of total cholesterol (174.0±45.7mg/dL) lower than non-attempters (193.9±42.6mg/dL) (p=0.004). This was confirmed among both violent (174.1±46.2mg/dL) and non-violent (173.8±46.1mg/dL) suicide attempters (p=0.035 and 0.016, respectively). However, logistic regression analyses, sequentially including demographic, clinical (comorbid alcohol and personality disorders), and biochemical factors, did not show any association between serum cholesterol and recent suicide attempts (p=0.172). Similar findings were observed in multinomial logistic regression analyses, for both violent (p=0.512) and non-violent (p=0.157) suicide attempts., Conclusions: Our findings do not support the hypothesis that serum cholesterol and suicide attempts are associated among subjects with major depressive disorder. The identification of valid and accessible biological markers of suicidal behaviors still represents a challenge for future research., (Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)