The kynurenine pathway in bipolar disorder: a meta-analysis on the peripheral blood levels of tryptophan and related metabolites.

Growing evidence suggests that a dysregulation of the kynurenine pathway (KP) occurs in bipolar disorder (BD). This systematic review and meta-analysis aimed at assessing the possible differences in peripheral blood levels of KP metabolites between individuals with BD and healthy controls. We searched Medline, Embase, and PsycInfo electronic databases for articles indexed up to February 2020. We included any observational study comparing the peripheral blood levels of at least one KP metabolite between adults with BD and healthy controls. Random-effects meta-analyses were carried out generating pooled standardized mean differences (SMDs). Heterogeneity between studies was estimated using the I2 index. Meta-regression and sensitivity analyses were conducted. Sixteen studies met inclusion criteria and were included in our study. Meta-analyses showed that individuals with BD have lower peripheral blood levels of tryptophan (SMD = -0.29), kynurenine (SMD = -0.28), kynurenic acid (SMD = -0.30), and xanthurenic acid (SMD = -0.55), along with lower kynurenic acid to kynurenine (SMD = -0.60) and kynurenic acid to quinolinic acid (SMD = -0.37) ratios, than healthy controls. Individuals with a manic episode showed the greatest reductions in tryptophan levels (SMD = -0.51), whereas kynurenic acid levels were more reduced among subjects in a depressive phase (SMD = -0.70). Meta-regression and sensitivity analyses confirmed our results. The findings of the present meta-analysis support the hypothesis of an abnormality of the KP in BD. Considering the partial inconsistency of the findings and the small-to-medium magnitude of the estimated effect sizes, additional research assessing possible mediators or confounders is needed.

Innovations in community-based mental health care: an overview of meta-analyses.

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.

Pre-Discharge Predictors of 1-Year Rehospitalization in Adolescents and Young Adults with Severe Mental Disorders: A Retrospective Cohort 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.

The association of kynurenine pathway metabolites with symptom severity and clinical features of bipolar disorder: An overview.

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.

Professionals' Digital Training for Child Maltreatment Prevention in the COVID-19 Era: A Pan-European Model.

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.

Disentangling the Association between ADHD and Alcohol Use Disorder in Individuals Suffering from Bipolar Disorder: A Systematic Review and Meta-Analysis.

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.

Some of us are most at risk: Systematic review and meta-analysis of correlates of depressive symptoms among healthcare workers during the SARS-CoV-2 outbreak.

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.