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Objective: Depression and neuropathy are frequent complications of type 2 diabetes. The current meta-analysis aimed to estimate the association between depression and neuropathy in subjects with type 2 diabetes. Methods: We systematically searched electronic databases for articles published up to February 2015, providing data on the association between depression and neuropathy in individuals with type 2 diabetes. No language restrictions were applied. The meta-analysis generated random-effect odds ratios with 95% confidence intervals (95% CI). Risk of publication bias and heterogeneity were estimated using the Egger test and I2 index, respectively. Leave-one-out analysis was performed. Data were analysed using stata. Results: Thirteen studies were included in the meta-analysis. Data on the association between depression and neuropathy were available for 3898 individuals with type 2 diabetes. Pooled analysis showed an association between depression and neuropathy, with an odds ratio of 2.01 (95% CI: 1.60–2.54; p < 0.001). There was no risk of publication bias (p = 0.064), and heterogeneity was moderate (I2 = 44.5%). Leave-one-out analysis confirmed consistency of the findings. The association appeared partly influenced by age, because studies selecting older people (sample mean age > 65 years) showed a slightly higher estimate for the association. Conclusions: We found an association between depression and neuropathy among people with type 2 diabetes. Because of the cross-sectional nature of included studies, the relationship between these two conditions might be bidirectional. Further research exploring factors that might moderate or mediate this association is needed. Targeted interventions for comorbid depression and neuropathy should be implemented in clinical practice. Copyright © 2016 John Wiley & Sons, Ltd.

Schizophrenia is a severe mental illness causing a high degree of disability. First- and second-generation antipsychotics (FGAs and SGAs) represent key resources for its acute and long-term management. Since a poor adherence to oral treatments may negatively impact the course of the disorder, long-acting injectable antipsychotics (LAIs) are often used to reduce clinical relapses. Notwithstanding their potential beneficial features, LAIs use in clinical practice remains somewhat hampered by the limited amount of relevant systematic information. This review thus aims at providing a clinical, practical guidance for the use of LAIs in the treatment of schizophrenia. We synthetized main information on indications, dosage, and administration of LAIs approved by the US Food and Drug Administration (FDA) and/or in EU countries, as well as evidence from the most recent systematic reviews and meta-analyses. Currently available information, though heterogeneous, shows that LAIs can prevent relapses and rehospitalizations, improving clinical outcomes and favouring sustained remission among people with schizophrenia. The use of SGA LAIs is supported by more robust evidence than FGA LAIs. Along with their positive impact on the prevention of treatment discontinuation, some LAIs might also enhance individual global functioning and quality of life, without additional adverse events or health-care costs, as compared with oral antipsychotics. Although which LAIs can be considered a first-choice option, as well as their superiority over oral antipsychotics, remain unclear issues, this review offers a comprehensive overview of information available on the use of LAIs for people with schizophrenia, providing clinicians with practical guidance in terms of efficacy and acceptability of single agents. Literature gaps and future research needs are also described.

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 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.

The COVID-19 pandemic has had a severe psychosocial impact on healthcare workers (HCWs). This systematic review and meta-analysis aimed at evaluating the association between individual features and depressive symptoms reported by HCWs during the pandemic. We searched Medline, Embase, and PsycInfo up to 23 June 2020. We included cross-sectional studies testing the association between individual correlates and depressive symptoms in HCWs during the SARS-CoV-2 outbreak. Fourteen studies met inclusion criteria, involving 14,173 HCWs (3,070 with depressive symptoms). Women (OR = 1.50; 95 %CI: 1.28–1.76; I2 = 40.0 %), individuals with suspected/confirmed COVID-19 (OR = 2.10; 95 %CI: 1.64–2.69; I2 = 0 %), and those with an infected family member or friend (OR = 1.67; 95 %CI: 1.37–2.04; I2 = 0%) were more likely to report depressive features, which, instead, were less frequent among doctors (compared with nurses) (OR = 0.80; 95 %CI: 0.66–0.98; I2 = 48.2 %) and HCWs who felt adequately protected (OR = 0.48; 95 %CI: 0.32–0.72; I2 = 36.3 %). Our study provided timely evidence on the correlates of depressive symptoms among HCWs during the pandemic. Early screening is crucial to develop tailored health interventions, redesigning the response to COVID-19.

Background The balance between neurotoxic and neuroprotective effects of kynurenine pathway (KP) components has been recently proposed as a key element in the pathophysiology of bipolar disorder (BD) and related mood episodes. This comprehensive overview explored the link of KP with symptom severity and other clinical features of BD. Methods We searched Medline, Embase, and PsycInfo electronic databases for studies assessing the association of peripheral and/or central concentrations of KP metabolites with putative clinical features, including symptom severity and other clinical domains in BD. Results We included the findings of 13 observational studies investigating the possible variations of KP metabolites according to symptom severity, psychotic features, suicidal behaviors, and sleep disturbances in BD. Studies testing the relationship between KP metabolites and depression severity generated mixed and inconsistent findings. No statistically significant correlations with manic symptoms were found. Moreover, heterogeneous variations of the KP across different clinical domains were shown. Few available studies found (a) higher levels of cerebrospinal fluid kynurenic acid and lower of plasma quinolinic acid in BD with psychotic features, (b) lower central and peripheral picolinic acid levels in BD with suicide attempts, and (c) no significant correlations between KP metabolites and BD-related sleep disturbances. Conclusions An imbalance of KP metabolism toward the neurotoxic branches is likely to occur in people with BD, though evidence on variations according to specific clinical features of BD is less clear. Additional research is needed to clarify the role of KP in the etiopathogenesis of BD and related clinical features.

The brain-derived neurotrophic factor (BDNF) has received considerable attention as a potential biomarker of major depressive disorder (MDD) and antidepressant response. We conducted an overview of meta-analyses investigating the relationship of BDNF with MDD, related clinical features, and antidepressant treatment. Based on a systematic screening on main electronic databases, 11 systematic reviews with meta-analyses were included. Available evidence suggests that people with MDD have peripheral and central BDNF levels lower than non-depressed individuals. A negative correlation between blood BDNF and symptom severity emerged, while no association with suicidality was detected. Moreover, an increase in blood BDNF levels after antidepressant treatment, proportional to symptom improvement, was reported. BDNF levels seem to be increased in both treatment responders and remitters, remaining stable in non-responders. Conversely, no variations of BDNF concentrations after non-pharmacological interventions (electroconvulsive therapy, repetitive transcranial magnetic stimulation, and physical activity) were found. The findings of this overview appear consistent with the neurotrophic hypothesis of depression, suggesting that BDNF may play a role in both MDD pathophysiology and pharmacological treatment response.

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.

Introduction: Pteridines, such as neopterin, biopterin, and tetrahydrobiopterin (BH4), 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 I2 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 (I2 = 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 (I2 = 77.9%) and quality of studies. Finally, no sufficient data were available for a meta-analysis on BH4. Conclusions: As a whole, our work partly supports the hypothesis of an imbalance of pteridine metabolism in depression.

Background The purpose was to systematically investigate which pharmacological strategies are effective to reduce the risk of violence among patients with Schizophrenia Spectrum Disorders (SSD) in forensic settings. Methods For this systematic review six electronic data bases were searched. Two researchers independently screened the 6,003 abstracts resulting in 143 potential papers. These were then analyzed in detail by two independent researchers. Of these, 133 were excluded for various reasons leaving 10 articles in the present review. Results Of the 10 articles included, five were merely observational, and three were pre-post studies without controls. One study applied a matched case-control design and one was a non-randomized controlled trial. Clozapine was investigated most frequently, followed by olanzapine and risperidone. Often, outcome measures were specific to the study and sample sizes were small. Frequently, relevant methodological information was missing. Due to heterogeneous study designs and outcomes meta-analytic methods could not be applied. Conclusion Due to substantial methodological limitations it is difficult to draw any firm conclusions about the most effective pharmacological strategies to reduce the risk of violence in patents with SSD in forensic psychiatry settings. Studies applying more rigorous methods regarding case-definition, outcome measures, sample sizes, and study designs are urgently needed.

Funding: This research is part of the ERICA project funded by the European Union’s Rights, Equality and Citizenship Programme (2014–2020). GA 856760. Child maltreatment (CM) has been enormously studied. However, a preventive practice still requires comprehensive and effective instruments to assess the risks for CM in a family context. The aim of this study is to describe the development process of an evidence-based CM risk assessment instrument (Family Needs Checklist, FNC) for primary prevention online utilization. This article reports the development process of the checklist and its mobile application, consisting of a systematic literature review, identification of known risk factors using the content analysis method, and generation of the checklist, including a multidisciplinary group in the design and feedback. As a result, a comprehensive and compact checklist was developed to be used by parents or caregivers as a self-referral instrument with an option to be used with professionals as a basis for joint conversations. The FNC consists of parental, family-, and child-related risk factors. Based on the international evidence, the online application consists of knowledge about different CM types, information about risk factors and protective factors as well as recommendations and guidance to support services. The FNC is based on robust evidence on known risk factors causing CM in families. It can be used for primary prevention utilization in the general population. Publisher PDF

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.

Background Systematic data on clinical correlates of mixed features in bipolar disorder are not available, so far. We conducted a systematic review and meta-analysis estimating the association between DSM-5 mixed features and candidate characteristics in depressive and manic/hypomanic episodes. Methods We included observational studies indexed in the main electronic databases. The association between DSM-5 mixed features and relevant correlates was estimated using odds ratio (OR) and standardized mean difference (SMD) with 95% confidence intervals (CIs), for categorical and continuous variables, respectively. Analyses were based on random effects models. Results Eight studies were included, involving 3070 individuals (1495 with a major depressive episode and 1575 with hypo/manic episode). No clinical characteristics were associated with mixed features in subjects with a depressive episode. Among subjects with a manic/hypomanic episode, those with mixed features were more likely to have a history of suicide attempts (OR: 2.37; 95%CI: 1.42 to 3.94; I2=39.7%), co-occurring anxiety disorders (OR: 2.67; 95%CI: 1.28 to 5.57; I2=0%), and a rapid cycling course (OR=4.23; 95%CI: 1.29 to 13.81; I2=0%), with less severe manic symptoms (SMD=-0.40; 95%CI: -0.65 to -0.16; I2=0%). Limitations (1) the heterogeneity of methods across studies and the inconsistency of findings; (2) the limited amount of data on correlates of DSM-5 mixed features; (3) the possible influence of publication bias. Conclusions Findings of this meta-analysis show that mixed features among individuals with a manic/hypomanic episode may identify a special clinical population, characterized not only by depressive symptoms, but also by anxiety, rapid cycling, and suicidality.

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.

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.

Background: A dose-response association, suggesting that heavy cannabis users are more likely to report depressive disorders, has been hypothesized. However, evidence is not conclusive, and we aimed at testing the existence of a linear association between different levels of cannabis use and depressive disorders using large, representative, repeated surveys. Methods: We examined prevalence rates of different levels of past-year cannabis use and major depressive episode (MDE), separately for young people (12–17 years) and adults (18–64 years), using data between 2006 and 2015 from the National Survey on Drug Use and Health. Prevalence rates estimates with 95% confidence intervals were computed, and the association between past-year MDE and cannabis use was assessed. We then investigated whether time-period trends existed for MDE and, if so, whether these differed by cannabis use levels. Models included both time period, to evaluate trend changes in past-year MDE from 2006 to 2015, and time period by cannabis level interaction terms. Results: Cannabis users were more likely, using both single-year and pooled survey data, to have suffered from MDE in the past year. Multiple logistic regression models, after adjusting for time period, age, and gender, showed an association between MDE and cannabis use, regardless of its levels. However, a roughly dose-response relationship was detectable only for adults. Trends in past-year MDE prevalence rates among subjects with different levels of cannabis use did not differ from trends among nonusers. Women were more likely to report concurrent past-year MDE and cannabis use than men. Conclusions: Cannabis users have consistently higher prevalence rates of depressive disorders compared with nonusers, suggesting the need for integrated screening and treatment programs to tackle this comorbid condition.

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.

Introduction Depression is a highly prevalent condition in the elderly, with a vast impact on quality of life, life expectancy, and medical outcomes. Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed agents in this condition and, although generally safe, tolerability issues cannot be overlooked. Vortioxetine is an antidepressant with a novel mechanism of action. Based on studies to date, it may have a promising tolerability profile in the elderly, as it does not adversely affect psychomotor or cognitive performance and does not alter cardiovascular and endocrine parameters. The present study aims to assess the tolerability profile of vortioxetine in comparison with the SSRIs considered as a single group in elderly participants with depression. The rate of participants withdrawing from treatment due to adverse events after 6 months of follow up will be the primary outcome. Methods and analysis This is a pragmatic, multicentre, open-label, parallel-group, superiority, randomized trial funded by the Italian Medicines Agency (AIFA - Agenzia Italiana del Farmaco). Thirteen Italian Community Psychiatric Services will consecutively enrol elderly participants suffering from an episode of major depression over a period of 12 months. Participants will be assessed at baseline and after 1, 3 and 6 months of follow up. At each time point, the following validated rating scales will be administered: Montgomery–Åsberg Depression Rating Scale (MADRS), Antidepressant Side-Effect Checklist (ASEC), EuroQual 5 Dimensions (EQ-5D), Short Blessed Test (SBT), and Charlson Age-Comorbidity Index (CACI). Outcome assessors and the statistician will be masked to treatment allocation. A total of 358 participants (179 in each group) will be enrolled. Ethics and dissemination This study will fully adhere to the ICH E6 Guideline for Good Clinical Practice. Participants’ data will be managed and safeguarded according to the European Data Protection Regulation 2016/679. An external Ethical Advisory Board will help guarantee high ethical standards. Trial registration Clinicaltrials.gov: NCT03779789, Registered on 19 December 2018. Submitted on 19 December. EudraCT number: 2018–001444-66. Trial status Protocol version 1.5; 09/06/2018. Recruitment started In February 2019 and it is ongoing. It is expected to end approximately on 30 September 2021.

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.

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.

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; I2 = 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.

Pathophysiological mechanisms of major depressive disorder (MDD) seem to be associated with oxidative stress pathways and altered purinergic metabolism. We conducted a systematic review and meta-analysis to estimate if subjects with MDD might have reduced levels of antioxidant uric acid, considering also potential influence of antidepressant treatment. We searched the main Electronic Databases, identifying 14 studies that met our inclusion criteria. Meta-analyses were carried out generating pooled Hedges' g and mean differences (MDs), using random-effects models. Heterogeneity across studies and risk of publication bias were estimated using standard methods. Relevant sensitivity and meta-regression analyses were conducted. Subjects with MDD had levels of uric acid lower than healthy controls (Hedges' g = -0.30; p = 0.003). Overall between-study heterogeneity was high (I 2 = 76.3%). The effect was significant among studies including drug naive/free MDD individuals (Hedges' g = -0.55; p = 0.023), but not among those involving treated subjects (Hedges' g = -0.15; p = 0.062). Relevant quality- and heterogeneity-based sensitivity analyses, as well as meta-regressions, confirmed these findings. In addition, uric acid levels significantly, though inconsistently (I 2 = 79.2%), increased after treatment (MD = +0.71 mg/dL; p

Background: A functional polymorphism in the catechol-O-methyltransferase (COMT) gene (Val158Met) appears to influence cognition in people with alcohol/substance use disorders (AUD/SUD) and in those with psychosis. Methods: To explore the potential moderating effect of these factors, a cross-sectional study was conducted, randomly recruiting subjects with DSM-IV diagnosis of schizophrenia. AUD/SUD was rigorously assessed, as well as COMT Val158Met polymorphism. Executive control functioning was measured using the Intra-Extra Dimensional Set Shift (IED). The effect of a possible interaction between comorbid AUD/SUD and COMT Val158Met polymorphism on IED scores was explored. Results: Subjects with schizophrenia, comorbid AUD/SUD, and MetMet carriers for SNP rs4680 of the COMT gene showed worse performance on IED completed stages scores, as compared with individuals with ValVal genotype. However, among subjects without AUD/SUD, those with the MetMet variant performed better than people carrying ValVal genotype. Conclusions: This study is the first to date examining the impact of COMT on cognition in a highly representative sample of people with schizophrenia and comorbid AUD/SUD. Differential moderating effects of COMT Val/Met genotype variations may similarly influence executive functions in people with schizophrenia and comorbid AUD/SUD.

Background: In the past decade, several smoking cessation interventions have been developed and implemented through information and communication technology (ICT). Evidence suggests that they might be suitable for large-scale public health interventions, based on updated communication media characteristics in terms of interplay between technology and graphical user interface, reaching high numbers of individuals. Objectives: We aimed at estimating web/text-based interventions effectiveness as compared with approaches routinely used for general population, that is smoking assessment or non-electronic self-help materials. Methods: A systematic review and meta-analysis was performed searching through PubMed, Embase and PsycInfo databases, as well as references of relevant papers. Heterogeneity and risk of bias were evaluated following standard methods. In addition, we performed meta-regression analyses testing if candidate covariates moderate the overall effect. Results: Slight but significant effectiveness was found for eHealth interventions over control conditions (RR = 1.28, 95% CI: 1.14–1.45). Meta-regressions showed similar findings for web- and text-based interventions. The effect seemed moderated by the follow-up period, being higher at 3 months and lower at 6/7 months follow-up. Conclusions: Our results outline moderate effectiveness of web/text-based interventions. However, a paucity of properly controlled studies and lack of information on several effect modifiers still hamper the development and implementation of smoking cessation interventions through ICT.

BackgroundSince bipolar disorder seems to be associated with purinergic system dysfunction, allopurinol might be effective in treating symptoms of mania.AimsTo estimate the efficacy and tolerability of allopurinol as adjunctive treatment for mania symptoms in people with bipolar affective disorder.MethodWe conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) comparing the effects of adjunctive allopurinol and placebo on mania symptom changes.ResultsFive RCTs were included in the meta-analysis. Participants with allopurinol augmentation had a significantly greater decrease in mania symptoms than those with placebo (SMD= −0.34, P = 0.007), especially in people with the most severe forms of mania. Remission rates, although based on only two studies (n = 177), were significantly higher among individuals receiving allopurinol, whereas for discontinuation and side-effects no difference was found.ConclusionsOur finding of a small to moderate effect size and overall low evidence for add-on allopurinol in reducing mania symptoms indicate that its use in routine practice needs further elucidation.

BackgroundThe interaction between positive, negative and depressive symptoms experienced by people with schizophrenia is complex. We used longitudinal data to test the hypothesis that depressive symptoms mediate the links between positive and negative symptoms.MethodsWe analyzed data from the European Schizophrenia Cohort, randomly sampled from outpatient services in France, Germany and the UK (N = 1208). Initial measures were repeated after 6 and 12 months. Depressive symptoms were identified using the Calgary Depression Scale for Schizophrenia (CDSS), while positive and negative symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Latent variable structural equation modelling was used to investigate the mediating role of depression assessed at 6 months in relation to the longitudinal association between positive symptoms at baseline and negative symptoms at 12 months.ResultsWe found longitudinal associations between positive symptoms at baseline and negative symptoms at 12 months, as well as between both of these and CDSS levels at 6 months. However depression did not mediate the longitudinal association between PANSS scores; all the effect was direct.ConclusionsOur findings are incompatible with a mediating function for depression on the pathway from positive to negative symptoms, at least on this timescale. The role of depression in schizophrenic disorders remains a challenge for categorical and hierarchical diagnostic systems alike. Future research should analyze specific domains of both depressive and negative symptoms (e.g. motivational and hedonic impairments). The clinical management of negative symptoms using antidepressant treatments may need to be reconsidered.

We aimed at clarifying the strength and consistency of the association between cannabis use disorder and suicide attempts in bipolar disorder. We conducted a systematic review and meta-analysis of observational studies providing cross-sectional and longitudinal data on this association. We screened articles indexed in Medline, Embase, PsycINFO databases up to July 2018. The random-effects meta-analysis, based on 6375 subjects from eleven studies, estimated a cross-sectional association between cannabis use disorder and history of suicide attempts (OR = 1.35; p = 0.01; I2 = 41.7%). Meta-regression analyses showed that effect size was not influenced by any study characteristics. Publication bias was not detectable. We could not perform a meta-analysis exploring the longitudinal association between cannabis use disorder and suicide attempts, due to the lack of suitable data. The current evidence highlights a weak association between cannabis use disorder and suicidal attempts in bipolar disorder. Due to the cross-sectional design of included studies, causal inferences could not be explored.

Evidence for an association between impaired facial emotion recognition and violence in people with schizophrenia is inconclusive. In particular, the role of misidentification patterns involving specific emotions such as anger and the influence of clinical characteristics on this association remain unclear. In this study, we compared facial emotion recognition performance in age- and gender-matched schizophrenia spectrum disorders subjects with (N = 52) and without (N = 52) a history of violence. Data on current symptom severity, Cluster B personality status, past victimization, and alcohol and substance misuse were also collected. Compared to those without, subjects with a history of violence showed worse facial emotion recognition performances, involving anger, fear, disgust, sadness, and happiness. When formally testing the reporting of angry faces, evidence of enhanced sensitivity to anger was not supported. Finally, when the impact of current symptoms was assessed, higher severity of activation symptoms, including motor hyperactivity, elevated mood, excitement and distractibility, mediated the relationship between history of violence and poor facial emotion recognition performance. As a whole, our findings seem to support the role of perceptual deficits involving different emotions as well as of a mediation played by activation symptoms. Facial emotion recognition deficits associated with the propensity to violence, as well certain symptoms mediating their relationship, should be targeted by specific treatment approaches.

BACKGROUND: There is a lack of studies testing accuracy of fast screening methods for alcohol use disorder in mental health settings. We aimed at estimating clinical utility of a standard single-item test for case finding and screening of DSM-5 alcohol use disorder among individuals suffering from anxiety and mood disorders. METHODS: We recruited adults consecutively referred, in a 12-month period, to an outpatient clinic for anxiety and depressive disorders. We assessed the National Institute on Alcohol Abuse and Alcoholism (NIAAA) single-item test, using the Mini- International Neuropsychiatric Interview (MINI), plus an additional item of Composite International Diagnostic Interview (CIDI) for craving, as reference standard to diagnose a current DSM-5 alcohol use disorder. We estimated sensitivity and specificity of the single-item test, as well as positive and negative Clinical Utility Indexes (CUIs). RESULTS: 242 subjects with anxiety and mood disorders were included. The NIAAA single-item test showed high sensitivity (91.9%) and specificity (91.2%) for DSM-5 alcohol use disorder. The positive CUI was 0.601, whereas the negative one was 0.898, with excellent values also accounting for main individual characteristics (age, gender, diagnosis, psychological distress levels, smoking status). DISCUSSION: Testing for relevant indexes, we found an excellent clinical utility of the NIAAA single-item test for screening true negative cases. Our findings support a routine use of reliable methods for rapid screening in similar mental health settings.Copyright © 2016 Elsevier Ireland Ltd. All rights reserved. Language: en

Purpose Binge drinking (BD) is common among young people. E-Health apps are attractive to them and may be useful for enhancing awareness. We aimed to investigate the impact of a publicly available evidence-based e-Health app (Digital–Alcohol Risk Alertness Notifying Network for Adolescents and Young Adults [D-ARIANNA]), estimating current risk of BD by questions, matching identified risk factors, and providing in percent an overall risk score, accompanied by appropriate images showing mostly contributing factors in summary graphics. Methods A natural, quasi-experimental, pre-/post-test study was conducted. Subjects were recruited in pubs, clubs, discos, or live music events. They were requested to self-administer D-ARIANNA and were re-evaluated after two further weeks. Results Young (18–24 years) people (N = 590) reported reduced BD at follow-up (18% vs. 37% at baseline). To exclude systematic errors involving those lost at follow-up (14%), the diminution in BD was confirmed in an appropriate generalized estimating equation model with unweighted data on a last observation carried forward basis. Conclusions Our study provides evidence of population-level benefit at 2 weeks, attained with D-ARIANNA. This can be disseminated easily and economically among young people. However, additional components, including regular feedback and repeated administration by gamification, may be required to make this app suitable for longer term impact.

Objectives: The aim of this systematic review and meta-analysis was to estimate the association between distinct types of child abuse-sexual (CSA), physical (CPA), and emotional (CEA)-and different eating disorders (EDs). Methods: Electronic databases were searched through January 2014. Studies reporting rates of CSA, CPA, and CEA in people with anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED), as compared with individuals without EDs, were included. Pooled analyses were based on odds ratios (ORs), with relevant 95% confidence intervals (CIs), weighting each study with inverse variance models with random effects. Risk of publication bias was estimated. Results: Thirty-two of 1714 studies assessed for eligibility met the inclusion criteria, involving more than 14,000 individuals. The association between EDs and any child abuse showed a random-effects pooled OR of 3.21 (95% CI = 2.29-4.51, p

People with alcohol and substance use disorders (AUDs/SUDs) show worse facial emotion recognition (FER) than controls, though magnitude and potential moderators remain unknown. The aim of this meta-analysis was to estimate the association between AUDs, SUDs and FER impairment. Electronic databases were searched through April 2015. Pooled analyses were based on standardized mean differences between index and control groups with 95% confidence intervals, weighting each study with random effects inverse variance models. Risk of publication bias and role of potential moderators, including task type, were explored. Nineteen of 70 studies assessed for eligibility met the inclusion criteria, comprising 1352 individuals, of whom 714 (53%) had AUDs or SUDs. The association between substance related disorders and FER performance showed an effect size of -0.67 (-0.95, -0.39), and -0.65 (-0.93, -0.37) for AUDs and SUDs, respectively. There was no publication bias and subgroup and sensitivity analyses based on potential moderators confirmed core results. Future longitudinal research should confirm these findings, clarifying the role of specific clinical issues of AUDs and SUDs.

A fair amount of subjects with schizophrenia do not respond to clozapine and are defined ‘ultra-resistant’. In this systematic review and meta-analysis, we tested the efficacy of adjunctive second-generation antipsychotics (SGAs) for main symptom domains (positive, negative, and depressive symptoms) in individuals with clozapine-resistant schizophrenia. We searched main electronic databases till December 2017. We included twelve double-blind, randomized, placebo-controlled trials (RCTs), evaluating the efficacy of SGAs for clozapine non/partial responders. We did not find any difference between SGAs and placebo (standardized mean difference, SMD = −0.21; p = 0.170; I2 = 68.0%) in improving positive symptoms. The effect size varied according to RCT duration (p = 0.025) and assessment methods (p = 0.016). Low-moderate effects of SGAs on both negative (SMD = −0.38; p = 0.005; I2 = 62.7%) and depressive symptoms (SMD = −0.35; p = 0.003; I2 = 4.9%), were estimated. In sum, our meta-analysis highlights the lack of efficacy of SGAs as add-on treatment for positive symptoms in clozapine-resistant schizophrenia. A small benefit of SGAs was estimated for both negative and depressive symptoms. Further RCTs are needed to establish efficacy and tolerability of SGAs or other augmentation strategies for different symptoms of clozapine-resistant schizophrenia.

Background Post stroke depression (PSD) is a common and serious complication after stroke. In this systematic review and meta-analysis, we evaluated the association between early PSD and mortality, considering depressive symptoms occurring within the first three months after the neurological event. Methods This meta-analysis was conducted following Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines and based on studies indexed till May 2018 in PubMed and Web of Science databases. The relative risk (RR) for mortality in individuals with PSD, as compared with non-depressed ones, was estimated. Findings were pooled according to a random-effects model. Meta-regression and subgroup analyses were carried out. Results We included seven studies, accounting for 119,075 individuals, of whom 17,609 suffering from an early PSD. We found higher rates of mortality in subjects with PSD as compared with non-depressed ones (RR = 1.50; 95%CI: 1.28 to 1.75; p

Objectives Binge drinking (BD) among young people has significant public health implications. Thus, there is the need to target users most at risk. We estimated the discriminative accuracy of an innovative model nested in a recently developed e-Health app (Digital-Alcohol RIsk Alertness Notifying Network for Adolescents and young adults [D-ARIANNA]) for BD in young people, examining its performance to predict short-term BD episodes. Methods We consecutively recruited young adults in pubs, discos, or live music events. Participants self-administered the app D-ARIANNA, which incorporates an evidence-based risk estimation model for the dependent variable BD. They were re-evaluated after 2 weeks using a single-item BD behavior as reference. We estimated D-ARIANNA discriminative ability through measures of sensitivity and specificity, and also likelihood ratios. ROC curve analyses were carried out, exploring variability of discriminative ability across subgroups. Results The analyses included 507 subjects, of whom 18% reported at least 1 BD episode at follow-up. The majority of these had been identified as at high/moderate or high risk (65%) at induction. Higher scores from the D-ARIANNA risk estimation model reflected an increase in the likelihood of BD. Additional risk factors such as high pocket money availability and alcohol expectancies influence the predictive ability of the model. Conclusions The D-ARIANNA model showed an appreciable, though modest, predictive ability for subsequent BD episodes. Post-hoc model showed slightly better predictive properties. Using up-to-date technology, D-ARIANNA appears an innovative and promising screening tool for BD among young people. Long-term impact remains to be established, and also the role of additional social and environmental factors.

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.

Background This study assessed the efficacy of the Falloon model of psychoeducational family intervention (PFI), originally developed for schizophrenia management and adapted to bipolar I disorder. The efficacy of the intervention was evaluated in terms of improvement of patients׳ social functioning and reduction of family burden. Methods This was a multicentre, real-world, controlled, outpatient trial carried out in 11 randomly recruited Italian mental health centres. Enroled patients and key-relatives were consecutively allocated either to receive PFI and Treatment As Usual (TAU) or to a waiting list receiving TAU alone. The efficacy of the intervention was evaluated in terms of improvement in patients׳ social functioning (primary outcome) and reduction of family burden (secondary outcome). Results Of the 137 recruited families, 70 were allocated to the experimental group and 67 to the control group. At the end of the intervention, significant improvements in patients׳ social functioning and in relatives׳ burden were found in the treated group compared to TAU. This effect of the intervention remained also after controlling for several confounding patient׳s socio-demographic and clinical factors. The experimental intervention had an impact also on other outcome measures, such as patients׳ clinical status and personal burden. Limitations Lack of an active control group. Conclusions The results of this study clearly show that the psychoeducational family intervention according to the Falloon model is effective in improving the social outcome of patients with bipolar I disorder.

BACKGROUND: Previous reports showed a high prevalence of obesity, diabetes, hypertension, and dyslipidemia among people suffering from posttraumatic stress disorder (PTSD). However, there is a lack of reviews that systematically analyze the relationship between PTSD and metabolic syndrome. We conducted a systematic review and meta-analysis aimed at estimating the association between PTSD and metabolic syndrome. METHODS: We systematically searched PubMed, Embase, and Web of Science. We included observational studies assessing the prevalence of metabolic syndrome in a sample with PTSD and in a comparison group without PTSD. Data were analyzed using Review manager 5.1. Odds ratios (OR) with 95% confidence intervals were used as an association measure for pooled analysis, based on a random-effects model. RESULTS: Six articles were eligible according to the inclusion criteria, for an overall number of 528 individuals suffering from PTSD and 846 controls without PTSD. The pooled OR for metabolic syndrome for people with PTSD was 1.37 (1.03-1.82). Statistical heterogeneity between the included studies was low (I(2)=22%). CONCLUSIONS: Despite some limitations, the findings of this systematic review and meta-analysis confirmed our hypothesis that individuals suffering from PTSD have a greater risk of metabolic syndrome. The potential role of unknown factors or mediators that might clarify the nature of this association needs further research.

Schizophrenia is likely to be associated with immunological abnormalities. However, antipsychotics may induce immunomodulatory effects, by influencing plasma cytokines. In order to distinguish these influences, we carried out a systematic review and meta-analysis exploring the acute effect of antipsychotics on candidate cytokines plasma levels (IL-1β, IL-2, IL-6, IL-17, IFN-γ, TNF-α) among drug-naïve subjects with first episode psychosis. We searched main Electronic Databases, identifying eight studies meeting our inclusion criteria. Plasma cytokines values were used to estimate standardized mean differences. Heterogeneity across studies was evaluated using the I2 index and controlled in relevant sensitivity analyses. IL-2 (p = 0.023) and IL-6 (p = 0.012) levels showed a significant decrease after four weeks of antipsychotic treatment. Relevant sensitivity analysis confirmed these findings. IL-1β had high between-study heterogeneity. However, leaving out one study, a significant decrease after treatment was found. IL-6 and IL-2, and possibly IL-1β, could be considered state markers, decreasing after antipsychotic treatment, whilst TNF-α, IL-17, and IFN-γ might be considered trait markers. Options for novel treatments in FEP, involving cytokine-modulating agents, should be further studied.

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 ± 45.7 mg/dL) lower than non-attempters (193.9 ± 42.6 mg/dL) (p = 0.004). This was confirmed among both violent (174.1 ± 46.2 mg/dL) and non-violent (173.8 ± 46.1 mg/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.

Background and Objectives: Since significant differences have been reported, we estimated agreement between DSM-5 and DSM-IV criteria for alcohol use disorder (AUD). Methods: We assessed 327 outpatients (mean age: 45.2 ± 13.4) with depressive or anxiety disorders. Results: Absolute differences in prevalence rates between DSM-5 and DSM-IV AUD ranged from −1.1% (subjects with anxiety disorders) to +1.8% (tobacco smokers). The agreement was excellent (k = 0.88), also accounting for specific subgroups (relevant k coefficients >0.80). Discussion and Conclusions: DSM-5 criteria did not inflate AUD rates. Scientific Significance: Our results have epidemiological significance since, unlike previous reports, we found diagnostic stability between new and old AUD criteria in this clinical population. (Am J Addict 2017;26:53–56).

A new “severity specifier” for bulimia nervosa (BN), based on the frequency of inappropriate weight compensatory behaviours (IWCBs), was added to the DSM-5 as a means of documenting heterogeneity and variability in the severity of the disorder. Yet, evidence for its validity in clinical populations, including prognostic significance for treatment outcome, is currently lacking. Existing data from 281 treatment-seeking patients with DSM-5 BN, who received the best available treatment for their disorder (manual-based cognitive behavioural therapy; CBT) in an outpatient setting, were re-analysed to examine whether these patients subgrouped based on the DSM-5 severity levels would show meaningful and consistent differences on (a) a range of clinical variables assessed at pre-treatment and (b) post-treatment abstinence from IWCBs. Results highlight that the mild, moderate, severe, and extreme severity groups were statistically distinguishable on 22 variables assessed at pre-treatment regarding eating disorder pathological features, maintenance factors of BN, associated (current) and lifetime psychopathology, social maladjustment and illness-specific functional impairment, and abstinence outcome. Mood intolerance, a maintenance factor of BN but external to eating disorder pathological features (typically addressed within CBT), emerged as the primary clinical variable distinguishing the severity groups showing a differential treatment response. Overall, the findings speak to the concurrent and predictive validity of the new DSM-5 severity criterion for BN and are important because a common benchmark informing patients, clinicians, and researchers about severity of the disorder and allowing severity fluctuation and patient’s progress to be tracked does not exist so far. Implications for future research are outlined.

Objective: Corrected QT (QTc) interval prolongation is often associated with use of first-generation antipsychotics (FGAs). However, other factors require appropriate consideration, including age and gender, the role of other known medications associated with QTc prolongation, and severe comorbid conditions, such as co-occurring alcohol abuse/dependence. We aimed to study potential mediating roles of different, related, candidate variables on QTc. Methods: We capitalized on data from a large (N = 2366), cross-sectional, national survey, the STAR Network QTc study, using a representative sample of people taking FGAs, and recruited from mental health services across Italy. Results: About one-third of the sample was treated with FGAs, and almost one-tenth of the subjects took a different, additional, drug known to cause QTc prolongation. Our findings confirmed that there is an impact from FGAs, age, gender, alcohol misuse, and concurrent risky drugs on QTc. However, comorbid alcohol abuse/dependence and concurrent risky drugs did not mediate the effect of FGAs on QTc. Conclusions: Our findings showed that FGAs, concurrent risky drugs, and alcohol use disorders prolonged QTc. FGAs had a direct effect on QTc, confirming the need for clinicians to monitor a risk that could lead to sudden unexplained death. Copyright © 2016 John Wiley & Sons, Ltd.

International audience; Little is known about the correlates of comorbid drug and alcohol ă dependence in people with schizophrenia outside the USA. We tested ă hypotheses that dependence on alcohol/drugs would be associated with ă more severe symptoms, and poorer psychosocial functioning and quality of ă life. The EuroSC Cohort study (N=1204), based in France, Germany and the ă UK, used semi-structured clinical interviews for diagnoses, and ă standardized tools to assess correlates. We used mixed models to compare ă outcomes between past-year comorbid dependence on alcohol/drugs, ă controlling for covariates and modelling both subject and country-level ă effects. Participants dependent on alcohol or drugs had fewer negative ă symptoms on PANSS than their non-dependent counterparts. However, those ă dependent on alcohol scored higher on PANSS general psychopathology than ă those who were not, or dependent only on drugs. People with ă schizophrenia dependent on drugs had poorer quality of life, more ă extrapyramidal side effects, and scored worse on Global Assessment of ă Functioning (GAF) than those without dependence. People with alcohol ă dependence reported more reasons for non-compliance with medication, and ă poorer functioning on GAF, though not on Global Assessment of Relational ă Functioning. In people with schizophrenia, comorbid dependence on ă alcohol or drugs is associated with impaired clinical and psycho social ă adjustment, and poorer quality of life. (C) 2016 Elsevier Ireland Ltd. ă All rights reserved.

Background: People with schizophrenia are more likely than general population to suffer from metabolic abnormalities, with second-generation antipsychotics (SGAs) increasing the risk. Low plasma adiponectin levels may lead to metabolic dysregulations but evidence in people with schizophrenia, especially for the role of SGAs, is still inconclusive. Objective: To compare plasma adiponectin levels between people with schizophrenia and healthy controls, and to estimate the relative effect of schizophrenia and SGAs on adiponectin. Methods: We performed a systematic review and meta-analysis of observational studies published up to 13 June 2014 in main electronic databases. Pooled standardized mean differences (SMDs) between index and control groups were generated. Appropriate subanalyses and additional subgroup analyses were carried out. Results: Data from 2735 individuals, 1013 with and 1722 without schizophrenia, respectively, were analysed. Schizophrenia was not associated with lower adiponectin levels (SMD of -0.28, 95%CI: -0.59, 0.04; p=. 0.09). However, individuals with schizophrenia taking SGAs had plasma levels significantly lower than controls (. p=. 0.002), which was not the case of drug free/drug naïve subjects (. p=. 0.52). As regards single antipsychotic drugs clozapine (. p