Objectives: The kynurenine (KYN) pathway has been attracting attention as a relevant pathway in schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). We conducted a systematic review and meta-analysis of studies examining KYN pathway metabolites from cerebrospinal fluid (CSF) samples in SZ, BD, and MDD. Methods: The PubMed and Scopus databases were systematically searched to identify peer-reviewed case-control studies published until April 2022 that assessed KYN metabolites, namely, tryptophan (TRP), KYN, kynurenic acid (KA), quinolinic acid (QA), and 3-hydroxykynurenine (3-HK), in subjects with SZ, BD, or MDD compared with healthy controls (HC). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. The random effects model method was selected for comparison of standardized mean differences (SMD) between two groups. Results: Twenty-three articles met the inclusion criteria (k = 8, k = 8, k = 11, for SZ, BD, and MDD, respectively). In SZ, KA levels were increased (SMD = 2.64, confidence interval [CI] = 1.16 to 4.13, p = 0.0005, I2 = 96%, k = 6, n=384). TRP (k = 5) and KYN (k = 4) did not differ significantly. In BD, TRP levels (k = 7) did not differ significantly. The level of KA was increased in MDD (k = 2), but the small number of studies precluded evaluation of statistical significance. Finally, in MDD, although some studies tended to show an increased level of KYN in those with remission vs. decreased levels in those with current depression, no significant difference was found in any KYN metabolite levels. Similarly, an increased level of QA was found, but the number of studies (k = 2) was small. Conclusion: KA, which has possibly neuroprotective effects, is increased in SZ. QA, which has neurotoxic effects, may be increased in MDD. There were no alterations in BD. Alterations in the KYN pathway may occur based on population characteristics and mood states. Future studies should explore the utility of these metabolites as biomarkers.

Crisis hotlines are direct communication systems, usually telephone-based, set up to prevent suicide. However, few studies have evaluated their effectiveness. The present study aims to perform a systematic review, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework, of the effectiveness of interventions through direct communication systems to reduce the number of suicides or suicide attempts. We searched the MEDLINE, Cochrane, SciELO, and ClinicaTrials.gov databases, and used the 2011 Oxford Centre for Evidence-Based Medicine Levels of Evidence classification. The literature search yielded 267 studies, of which 35 fulfilled the selection criteria. Although significant heterogeneity was found among studies, there is evidence that direct telephone interventions are effective when included in broader preventive protocols and provided by trained staff. Despite the limitations, which included heterogeneity of samples, designs, and outcome measures, we were able to design a protocol for the use of remote services to prevent suicide and suicide attempts. A hotline or similar system could be an effective intervention for broader suicide prevention programs. However, further research is necessary to specify which protocol components are key to enhance effectiveness. Systematic review registry number: PROSPERO CRD42020206517

Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) causes the coronavirus disease 2019 (COVID-19), which has been declared a public health emergency of international interest, with confirmed cases in most countries. COVID-19 presents manifestations that can range from asymptomatic or mild infections up to severe manifestations that lead to hospitalization and death. A growing amount of evidence indicates that the virus may cause neuroinvasion. Postmortem brain study findings have included edema, hemorrhage, hydrocephalus, atrophy, encephalitis, infarcts, swollen axons, myelin loss, gliosis, neuronal satellitosis, hypoxic-ischemic damage, arteriolosclerosis, leptomeningeal inflammation, neuronal loss, and axon degeneration. In addition, the COVID-19 pandemic is causing dangerous effects on the mental health of the world population, some of which can be attributed to its social impact (social distancing, financial issues, and quarantine). There is also a concern that environmental stressors, enhanced by psychological factors, are contributing to the emergence of psychiatric outcomes during the pandemic. Although clinical studies and diagnosing SARS-CoV-2-related neurological disease can be challenging, they are necessary to help define the manifestations and burden of COVID-19 in neurological and psychiatric symptoms during and after the pandemic. This review aims to present the neurobiology of coronavirus and postmortem neuropathological hallmarks.

Electrical and magnetic brain stimulation techniques present distinct mechanisms and efficacy in the acute treatment of depression. This was an umbrella review of meta-analyses of randomized controlled trials of brain stimulation techniques for managing acute major depressive episodes. A systematic review was performed in the PubMed/MEDLINE databases from inception until March 2020. We included the English language meta-analysis with the most randomized controlled trials on the effects of any brain stimulation technique vs. control in adults with an acute depressive episode. Continuous and dichotomous outcomes were assessed. A Measurement Tool to Assess Systematic Reviews-2 was applied and the credibility of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation framework. Seven meta-analyses were included (5,615 patients), providing evidence for different modalities of brain stimulation techniques. Three meta-analyses were evaluated as having high methodological quality, three as moderate, and one as low. The highest quality of evidence was found for high frequency-repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation, and bilateral rTMS. There is strong clinical research evidence to guide future clinical use of some techniques. Our results confirm the heterogeneity of the effects across these techniques, indicating that different mechanisms of action lead to different efficacy profiles.

This article continues our presentation of the Brazilian Psychiatric Association guidelines for the management of patients with suicidal behavior, with a focus on screening, intervention, postvention, prevention, and promotion. For the development of these guidelines, we conducted a systematic review of the MEDLINE (via PubMed), Cochrane Database of Systematic Reviews, Web of Science, and SciELO databases for research published from 1997 to 2020. Systematic reviews, clinical trials, and cohort/observational studies on screening, intervention, and prevention in suicidal behavior were included. This project involved 14 Brazilian psychiatry professionals and 1 psychologist selected by the Psychiatric Emergencies Committee of the Brazilian Psychiatric Association for their experience and knowledge in psychiatry and psychiatric emergencies. Publications were evaluated according to the 2011 Oxford Center for Evidence-Based Medicine (OCEBM) Levels of Evidence Classification. Eighty-five articles were reviewed (of 5,362 initially collected and 755 abstracts on the drug approach). Forms of screening, intervention, and prevention are presented. The intervention section presents evidence for psychotherapeutic and drug interventions. For the latter, it is important to remember that each medication is effective only for specific groups and should not replace treatment protocols. We maintain our recommendation for the use of universal screening plus intervention. Although the various studies differ in terms of the populations evaluated and several proposals are presented, there is already significant evidence for certain interventions. Suicidal behavior can be analyzed by evidence-based medicine protocols. Currently, the best strategy is to combine several techniques through the Safety Plan. Nevertheless, further research on the topic is needed to elucidate some approaches with particular potential for intervention and prevention. Systematic review registry number: CRD42020206517

Suicide is a global public health problem that causes the loss of more than 800,000 lives each year, principally among young people. In Brazil, the average mortality rate attributable to suicide is approximately 5.23 per 100,000 population. Although many guidelines have been published for the management of suicidal behavior, to date, there are no recent guidelines based on the principles of evidence-based medicine that apply to the reality of suicide in Brazil. The objective of this work is to provide key guidelines for managing patients with suicidal behavior in Brazil. This project involved 11 Brazilian psychiatry professionals selected by the Psychiatric Emergencies Committee (Comissão de Emergências Psiquiátricas) of the Brazilian Psychiatric Association for their experience and knowledge in psychiatry and psychiatric emergencies. For the development of these guidelines, 79 articles were reviewed (from 5,362 initially collected and 755 abstracts). In this review, we present definitions, risk and protective factors, assessments, and an introduction to the Safety Plan. Systematic review registry number: CRD42020206517

Abstract Ammonia is involved in the pathogenesis of neurological conditions associated with hyperammonemia, including hepatic encephalopathy. Few is known about the effects of gestational exposition to ammonia in the developing brain, and the possible long-term consequences of such exposure. We aimed to evaluate the effects of ammonia exposure during the gestation and the possible long-term cognitive alterations on pups. Eight female rats were divided into two groups: (1) control (saline solution); (2) ammonia (ammonium acetate, 2,5mmol/Kg). Each rat received a single subcutaneous injection during all gestational period. The brains from 1-day-old rats were obtained to the determination of thiobarbituric acid reactive species (TBARS), protein carbonyl and nitrite/nitrate levels. Some animals were followed 30 days after delivery and were subjected to the step-down inhibitory avoidance task. It was observed a significant increase in protein carbonyl, but not TBARS or nitrite/nitrate levels, in pups exposed to ammonia. Rats exposed to ammonia presented long-term cognitive impairment. Gestational exposition to ammonia induces protein oxidative damage in the neonatal rat brain, and long-term cognitive impairment.