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

Objective: Changes in the kynurenine pathway are recognized in psychiatric disorders, but their role in Alzheimer’s disease (AD) is less clear. We aimed to conduct a systematic review and meta-analysis to determine whether tryptophan and kynurenine pathway metabolites are altered in AD. Methods: We performed a systematic review and random-effects meta-analyses. Inclusion criteria were studies that compared AD and cognitively normal (CN) groups and assessed tryptophan or kynurenine pathway metabolites in cerebrospinal fluid or peripheral blood. Results: Twenty-two studies with a total of 1,356 participants (664 with AD and 692 CN individuals) were included. Tryptophan was decreased only in peripheral blood. The kynurenine-to-tryptophan ratio was only increased in peripheral blood of the AD group. 3-Hydroxykynurenine was decreased only in cerebrospinal fluid and showed higher variability in the CN group than the AD group. Kynurenic acid was increased in cerebrospinal fluid and decreased in peripheral blood. Finally, there were no changes in kynurenine and quinolinic acid between the groups. Conclusions: Our results suggested a shift toward the kynurenine pathway in both the brain and in the periphery, as well as a shift towards increased kynurenic acid production in the brain but decreased production in peripheral blood. In addition, our analysis indicated dissociation between the central and peripheral levels, as well as between plasma and serum for some of these metabolites. Finally, changes in the kynurenine pathway are suggested to be a core component of AD. More studies are warranted to verify and consolidate our results.

Resumen El objetivo de este trabajo fue evaluar la vulnerabilidad social, en función de las características de la población, como medio para indicar los posibles espacios intraurbanos con mayores posibilidades de dispersión y contagio por COVID-19. Sobre la base de variables que explican las características sociales y aumentan la vulnerabilidad de los individuos, se seleccionó la información del IBGE, se trató mediante análisis factorial y se cartografió, de acuerdo con la adaptación de la metodología desarrollada por el Centro de Estudios Sociales de Coimbra. La escala de cobertura elegida fue la de los sectores censales de tres municipios del estado de Rio Grande do Sul/Brasil. El análisis dio como resultado 21 variables que per-miten clasificar cinco dimensiones de la vulnerabilidad de las po-blaciones, indicando los lugares donde las acciones para prevenir el contagio deben ser más incisivas, dadas las características de la población, y se evidenció la vulnerabilidad de las periferias urbanas. La agrupación de la información mostró dimensiones sociales que denotan aspectos auxiliares para la comprensión del territorio y la vulnerabilidad social a escala local. La metodología demostrada puede adoptarse fácilmente en diferentes escalas y regiones del Brasil, y también en otros países. Este estudio permitirá adoptar decisiones encaminadas a evitar el contagio y subvencionar con información la elaboración de planes para la reanudación gradual de las actividades económicas y sociales.

Abstract This work aimed to evaluate social vulnerability based on population characteristics as a means to indicate the possible intra-ur-ban spaces with greater chances of dispersion and contagion by COVID-19. Based on variables that explain social characteristics and increase the vulnerability of individuals, information from IBGE was selected, treated by factor analysis and mapped, according to the adaptation of the methodology developed by the Centre for Social Studies in Coimbra. The scale of coverage chosen was that of census sectors, from three municipalities in the state of Rio Grande do Sul/Brazil. The analysis resulted in 21 variables that make it possible to classify five dimensions of the vulnerability of the populations, indicating the places where actions to prevent contagion should be more incisive, given the population characteristics, and the vulnerability of urban peripheries was evidenced. The grouping of information expressed social dimensions that denote aspects auxiliary to understanding the territory and social vulnerability on a local scale. The methodology demonstrated can be easily adopted in different scales and regions of Brazil, and also in other countries. This study will make it possible to make decisions aimed at avoiding contagion, and to subsidize with information the elaboration of plans for the gradual resumption of economic and social activities.

Résumé Ce travail visait à évaluer la vulnérabilité sociale sur la base des caractéristiques de la population afin d'indiquer les espaces intra-ur-bains possibles avec de plus grandes chances de dispersion et de contagion par COVID-19. Sur la base de variables qui expliquent les caractéristiques sociales et augmentent la vulnérabilité des individus, les informations de l'IBGE ont été sélectionnées, traitées par analyse factorielle et cartographiées, selon l'adaptation de la méthodologie développée par le Centre d'études sociales de Coimbra. L'échelle de couverture choisie a été celle des secteurs de recensement, de trois municipalités de l'État du Rio Grande do Sul/Brésil. L'analyse a donné lieu à 21 variables qui permettent de classer cinq dimensions de la vulnérabilité des populations, indiquant les endroits où les actions de prévention de la contagion devraient être plus incisives, compte tenu des caractéristiques de la population, et la vulnérabilité des périphéries urbaines a été mise en évidence. Le regroupement des informations exprime des dimensions sociales qui dénotent des aspects auxiliaires à la compréhension du territoire et de la vulnérabilité sociale à l'échelle locale. La méthodologie démontrée peut être facilement adoptée à différentes échelles et régions du Brésil, ainsi que dans d'autres pays. Cette étude permettra de prendre des décisions visant à éviter la contagion, et de subventionner par l'information l'élaboration de plans de reprise progressive des activités économiques et sociales.

Resumo Este trabalho teve por objetivo avaliar a vulnerabilidade social a partir de características da população como meio de indicar os possíveis espaços intraurbanos com maiores chances de dispersão e contágio por COVID-19. A partir de variáveis que explicitam características sociais e ampliam a vulnerabilidade dos indivíduos, foram selecionadas informações do IBGE, tratadas por análise fatorial e mapeadas, conforme adaptação da metodologia desenvolvida pelo Centro de Estudos Sociais, em Coimbra. A escala de abrangência escolhida foi a de setores censitários, a partir de três municípios do estado do Rio Grande do Sul/Brasil. A análise resultou em 21 variáveis que possibilitam classificar cinco dimensões da vulnerabilidade das populações, indicando os locais onde ações de prevenção ao contágio devem ser mais incisivas, dadas as características populacionais, e evidenciou-se a vulnerabilização de periferias urbanas. O agrupamento de informações expressou dimensões sociais que denotam aspectos auxiliares na compreensão do território e da vulnerabilidade social em escala local. A metodologia demonstrada pode ser facilmente adotada em diferentes escalas e regiões do Brasil, e também em outros países. Esse estudo possibilitará a tomada de decisões visando evitar o contágio, e subsidiar com informações a elaboração de planos para a retomada gradual das atividades econômicas e social.

While most patients with depression respond to pharmacotherapy and psychotherapy, about one-third will present treatment resistance to these interventions. For patients with treatment-resistant depression (TRD), invasive neurostimulation therapies such as vagus nerve stimulation, deep brain stimulation, and epidural cortical stimulation may be considered. We performed a narrative review of the published literature to identify papers discussing clinical studies with invasive neurostimulation therapies for TRD. After a database search and title and abstract screening, relevant English-language articles were analyzed. Vagus nerve stimulation, approved by the U.S. Food and Drug Administration as a TRD treatment, may take several months to show therapeutic benefits, and the average response rate varies from 15.2-83%. Deep brain stimulation studies have shown encouraging results, including rapid response rates (> 30%), despite conflicting findings from randomized controlled trials. Several brain regions, such as the subcallosal-cingulate gyrus, nucleus accumbens, ventral capsule/ventral striatum, anterior limb of the internal capsule, medial-forebrain bundle, lateral habenula, inferior-thalamic peduncle, and the bed-nucleus of the stria terminalis have been identified as key targets for TRD management. Epidural cortical stimulation, an invasive intervention with few reported cases, showed positive results (40-60% response), although more extensive trials are needed to confirm its potential in patients with TRD.

Treatment-resistant bipolar depression (TRBD) has been reported in about one-quarter of patients with bipolar disorders, and few interventions have shown clear and established effectiveness. We conducted a narrative review of the published medical literature to identify papers discussing treatment-resistant depression concepts and novel interventions for bipolar depression that focus on TRBD. We searched for potentially relevant English-language articles published in the last decade. Selected articles (based on the title and abstract) were retrieved for a more detailed evaluation. A number of promising new interventions, both pharmacological and non-pharmacological, are being investigated for TRBD treatment, including ketamine, lurasidone, D-cycloserine, pioglitazone, N-acetylcysteine, angiotensin-converting enzyme inhibitors, angiotensin II type 1 receptor blockers, cyclooxygenase 2 inhibitors, magnetic seizure therapy, intermittent theta-burst stimulation, deep transcranial magnetic stimulation, vagus nerve stimulation therapy, and deep brain stimulation. Although there is no consensus about the concept of TRBD, better clarification of the neurobiology associated with treatment non-response could help identify novel strategies. More research is warranted, mainly focusing on personalizing current treatments to optimize response and remission rates.

Abstract Cheese ripeness is an important step of cheese manufacturing that provides a kind of food with complex sensory characteristics and nuanced differences. The importance of generating rapid/easy consumer perception of a new product is without question. The aim was to evaluate the Santo Giorno cheese sensory profile, at different ripening times and with different starter cultures, evaluated by trained assessors and consumers using CATA questions. The two methods generated similar results. However, the results from CATA revealed that consumers are able to discriminate between cheeses with different ripening times but not describe them in detail. The application of the technique also made it possible to perceive that the two starter cultures used did not reflect different sensory elements and that the spicy and salty attributes are more easily perceived by consumers when evaluating ripened cheeses.

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.

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

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