Objectives: To determine the prevalence and correlates of treatment-resistant schizophrenia (TRS) through a systematic review and meta-analysis. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, an electronic search was performed in PubMed and Embase through May 17, 2022. All study designs that assessed a minimum of 20 schizophrenia-spectrum patients and provided data on TRS prevalence or allowed its calculation were included. Estimates were produced using a random-effects model meta-analysis. Results: The TRS prevalence across 50 studies (n = 29,390) was 36.7% (95%CI 33.1-40.5, p < 0.0001). The prevalence ranged from 22% (95%CI 18.4-25.8) in first-episode to 39.5% (95%CI 32.2-47.0) in multiple-episode samples (Q = 18.27, p < 0.0001). Primary treatment resistance, defined as no response from the first episode, was 23.6% (95%CI 20.5-26.8) vs. 9.3% (95%CI 6.8-12.2) for later-onset/secondary (≥ 6 months after initial treatment response). Longer illness duration and recruitment from long-term hospitals or clozapine clinics were associated with higher prevalence estimates. In meta-regression analyses, older age and poor functioning predicted greater TRS. When including only studies with lower bias risk, the TRS prevalence was 28.4%. Conclusion: Different study designs and recruitment strategies accounted for most of the observed heterogeneity in TRS prevalence rates. The results point to early-onset and later-onset TRS as two separate disease pathways requiring clinical attention. Registration number: PROSPERO CRD42018092033.

ABSTRACT Objective: The aim of this study was to compare the social cognition profiles of male adults with ASD (n = 15), SCHZ (n = 16) and controls (n = 20). Change the second sentence of the abstract. Methods: A cross-sectional assessment of social cognition domains with emotional face perception with eye tracking was performed, and two IQ measures (Verbal IQ and Performance IQ) (Wechsler Adult Intelligence Scale), and the DSM-IV Structured Clinical Interview were applied. Results: There were no significant differences in terms of average performance in social cognition tests or eye tracking tasks between the ASD and SCHZ groups. However, both had lower performances in most cases when compared to the control group. In the social cognition tasks, individuals in the control group performed better than both clinical groups. Conclusion: Although differences were identified between individuals with ASD and SCHZ, it was not possible to determine patterns or to differentiate the clinical groups.

RESUMO Objetivo: O objetivo deste estudo foi comparar os perfis de cognição social de adultos do sexo masculino com TEA (n = 15), SCHZ (n = 16) e controles (n = 20). Métodos: Foram aplicadas uma avaliação transversal dos domínios de cognição social com percepção emocional com rastreamento ocular, duas medidas de QI (QI verbal e QI de desempenho) (Escala de Inteligência Adulta de Wechsler) e a Entrevista Clínica Estruturada DSM-IV. Resultados: Não houve diferenças significativas em termos de desempenho médio em testes de cognição social ou tarefas de rastreamento ocular entre os grupos ASD e SCHZ. No entanto, ambos tiveram desempenhos mais baixos na maioria dos casos, quando comparados ao grupo controle. Nas tarefas de cognição social, os indivíduos do grupo controle tiveram melhor desempenho do que ambos os grupos clínicos. Conclusão: Embora tenham sido identificadas diferenças entre indivíduos com TEA e SCHZ, não foi possível determinar padrões ou diferenciar os grupos clínicos.

Abstract Introduction Prodromal characteristics of psychosis have been described for more than a century. Over the last three decades, a variety of studies have proposed methods to prospectively identify individuals (and youth in particular) who are at high risk of developing a psychotic disorder. These studies have validated various screening instruments and made them available in several languages. Here, we describe the translation into Brazilian Portuguese and cross-cultural adaptation of two such screening tools – the Prodromal Questionnaire-16 (PQ-16) and the Prevention through Risk Identification, Management, and Education (PRIME)-Screen. Method Two bilingual native speakers of Brazilian Portuguese translated the questionnaires from English. A native English speaker then performed back-translations into English. These back-translated versions were submitted to the original authors. They provided feedback and later approved the final versions. Results After translation and cross-cultural adaptation, no items needed to be changed in the adapted PQ-16 and four items were revised in the PRIME-Screen. After the peer-review process, we included two suggestions in the PQ-16 to facilitate use of the tool in our cultural and social contexts. The PRIME-Screen did not need further changes. Conclusion These new instruments can help screen Brazilian Portuguese-speaking patients who are at risk of psychosis in primary care.

Objective: The Identifying Depression Early in Adolescence Risk Score (IDEA-RS) was recently developed in Brazil using data from the Pelotas 1993 Birth Cohort to estimate the individualized probability of developing depression in adolescence. This model includes 11 sociodemographic variables and has been assessed in longitudinal studies from four other countries. We aimed to test the performance of IDEA-RS in an independent, community-based, school-attending sample within the same country: the Brazilian High-Risk Cohort. Methods: Standard external validation, refitted, and case mix-corrected models were used to predict depression among 1442 youth followed from a mean age of 13.5 years at baseline to 17.7 years at follow-up, using probabilities calculated with IDEA-RS coefficients. Results: The area under the curve was 0.65 for standard external validation, 0.70 for the case mix-corrected model, and 0.69 for the refitted model, with discrimination consistently above chance for predicting depression in the new dataset. There was some degree of miscalibration, corrected by model refitting (calibration-in-the-large reduced from 0.77 to 0). Conclusion: IDEA-RS was able to parse individuals with higher or lower probability of developing depression beyond chance in an independent Brazilian sample. Further steps should include model improvements and additional studies in populations with high levels of subclinical symptoms to improve clinical decision making.

ABSTRACT The article discusses biographical aspects of Rodrigo Melo Franco de Andrade related to the period prior to his position as head of Serviço do Patrimônio Histórico e Artístico Nacional (Sphan), which began in 1936. The proposed approach is justified in view of the existence of numerous gaps related to Rodrigo’s trajectory in the period in question, which are relevant to understand the reasons for his appointment to the position of first director of the institution. The results of the research point to the importance of the cultural and political weight of the Melo Franco family, and its strong engagement in the Revolution of 1930, as decisive in this indication, as well as its association with the journalist Assis Chateaubriand, who put his journalistic enterprises at Vargas’ service. These aspects were decisive for Rodrigo’s indication to assume the position of director of Sphan, which seems predestined today, despite his alienation in relation to heritage preservation issues until then.

RESUMO Este artigo aborda aspectos biográficos de Rodrigo Melo Franco de Andrade relativos ao período anterior a sua atuação à frente do Serviço do Patrimônio Histórico e Artístico Nacional (Sphan), iniciado em 1936. Justifica-se a abordagem proposta em função da existência de numerosas lacunas relativas à trajetória de Rodrigo no período em questão, consideradas relevantes para entender as razões de sua indicação ao cargo de primeiro diretor do órgão. Os resultados da pesquisa apontam a importância do lastro cultural e político da família Melo Franco e seu forte engajamento na Revolução de 1930, como decisivos nesta indicação, bem como sua associação com o jornalista Assis Chateaubriand, que colocou suas empresas jornalísticas a serviço de Vargas. A par de suas qualidades pessoais e intelectuais, tais aspectos foram decisivos para que Rodrigo assumisse a posição de diretor do Sphan, que hoje se afigura predestinada, a despeito de seu alheamento em relação à problemática da preservação do patrimônio até então.

Objective: Clozapine is a second-generation antipsychotic indicated for treatment-resistant schizophrenia. Studies in several countries have shown a low rate of clozapine use despite the fact that approximately 30% of schizophrenia cases are treatment-resistant. In Brazil, few studies have addressed the frequency and variety of antipsychotic use in individuals diagnosed with schizophrenia (ICD F20). The objective of this study was to measure the rates of clozapine use in this population in the last decade using Brazilian Ministry of Health data. Methods: Prescriptions made between 2010 and 2020 in all 26 states and the Federal District registered at the Outpatient Information System Database from the Brazilian Health System (SIASUS) were evaluated. Results: A total of 25,143,524 prescriptions were recorded in this period, with clozapine representing 8.86% of all antipsychotics. The most frequently prescribed antipsychotic for patients with schizophrenia was olanzapine (35.8%), followed by quetiapine (27.5%). From 2010 to 2020, the rate of clozapine prescriptions in Brazil increased from 7.2% to 10.9%. Conclusions: Despite a slight increase in prescriptions in the last decade, clozapine is still underutilized in Brazil.

The neurobiological factors associated with the emergence of major depressive disorder (MDD) in adolescence are still unclear. Previous cross-sectional studies have documented aberrant connectivity in resting-state functional magnetic resonance imaging (rs-fMRI) networks. However, whether these findings precede MDD onset has not been established. This scoping review mapped key methodological aspects and main findings of longitudinal rs-fMRI studies of MDD in adolescence. Three sets of neuroimaging methods to analyze rs-fMRI data were identified: seed-based analysis, independent component analysis, and network-based approaches. Main findings involved aberrant connectivity within and between the default mode network (DMN), the cognitive control network (CCN), and the salience network (SN). Accordingly, we utilized Menon’s (2011) triple-network model for neuropsychiatric disorders to summarize key results. Adolescent MDD was associated with hyperconnectivity within the SN and between DMN and SN, as well as hypoconnectivity within the CCN. These findings suggested that dysfunctional connectivity among the three main large-scale brain networks preceded MDD onset. However, there was high heterogeneity in neuroimaging methods and sampling procedures, which may limit comparisons between studies. Future studies should consider some level of harmonization for clinical instruments and neuroimaging methods.

Lack of diversity regarding genetic and environmental backgrounds weakens the generalization and clinical applicability of research findings on psychotic disorders. Notably, Latin Americans have been generally neglected in genetic studies, comprising less than 2% of genome-wide association study samples. But Latin American populations represent a unique opportunity for research, given the exceptionally high ethnic admixture of this group. Increasing genetic diversity is essential to improve the fine mapping of known regions associated with psychotic disorders, discover novel genetic associations, and replicate studies. Additionally, Latin America is characterized by massive social, political, and economic inequalities, all known risk factors for mental health issues, including psychotic disorders. This article aims to 1) discuss the challenges and advantages of studying Latin America’s particular genetic makeup and environmental context; 2) review previous studies conducted in the region; and 3) describe three Latin American research initiatives in progress: the Neuropsychiatric Genetics of Psychosis in Mexican Populations (NeuroMEX), the Paisa, and the Latin American Network for the Study of Early Psychosis (ANDES) studies.

Objective: To assess the efficacy of cannabidiol (CBD) in the management of crack-cocaine craving and the treatment of frequent withdrawal symptoms. Methods: Thirty-one men with a diagnosis of crack-cocaine dependence were enrolled in a randomized, double-blind, placebo-controlled trial. We applied neuropsychological tests and assessed craving intensity, anxiety and depression symptoms, and substance use patterns at baseline and at the end of the trial. The participants were treated with CBD 300 mg/day or placebo for 10 days. During this period, we used a technique to induce craving and assessed the intensity of symptoms before and after the induction procedure. Results: Craving levels reduced significantly over the 10 days of the trial, although no differences were found between the CBD and placebo groups. Craving induction was successful in both groups, with no significant differences between them. Indicators of anxiety, depression, and sleep alterations before and after treatment also did not differ across groups. Conclusion: Under the conditions of this trial, CBD was unable to interfere with symptoms of crack-cocaine withdrawal. Further studies with larger outpatient samples involving different doses and treatment periods would be desirable and timely to elucidate the potential of CBD to induce reductions in crack-cocaine self-administration.

Objective: To determine whether psychiatric and gaming pattern variables are associated with gaming disorder in a school-based sample. Methods: We analyzed data from the Brazilian High-Risk Cohort for Psychiatric Disorders, a community sample aged 10 to 18, using questionnaires on gaming use patterns. We applied the Gaming Addiction Scale to diagnose gaming disorder and the Development and Well-Being Behavior Assessment for other diagnoses. Results: Out of 407 subjects, 83 (20.4%) fulfilled the criteria for gaming disorder. More role-playing game players were diagnosed with gaming disorder that any other genre. Gaming disorder rates increased proportionally to the number of genres played. Playing online, being diagnosed with a mental disorder, and more hours of non-stop gaming were associated with higher rates of gaming disorder. When all variables (including age and gender) were considered in a logistic regression model, the number of genres played, the number of non-stop hours, the proportion of online games, and having a diagnosed mental disorder emerged as significant predictors of gaming disorder. Conclusion: Each variable seems to add further risk of gaming disorder among children and adolescents. Monitoring the length of gaming sessions, the number and type of genres played, time spent gaming online, and behavior changes may help parents or guardians identify unhealthy patterns of gaming behavior.

RESUMO Racional: O aumento da prevalência da obesidade levou ao aumento significativo da ocorrência de síndrome metabólica, fator de risco reconhecido para aumento da morbimortalidade por doenças cardiovasculares. A hiperglicemia ou diabetes mellitus do tipo 2, dislipidemia e hipertensão arterial são seus principais componentes. Desde 2015, diretrizes internacionais reconheceram os benefícios da cirurgia bariátrica em cada fator isolado desta síndrome. Objetivos: Avaliar o impacto do bypass gástrico em Y-de-Roux nesta síndrome comparando períodos pré e pós-operatório com análise laboratorial, e comparar a razão cintura/estatura e o IMC em relação a determinação do perfil de risco cardiometabólico. Métodos: Realizou-se um estudo retrospectivo com base prospectiva selecionando 80 pacientes submetidos à bypass gástrico em Y-de-Roux. Foram analisados o colesterol total, HDL, LDL, triglicerídeos, glicemia de jejum, hemoglobina glicada, insulina, índice de massa corpórea (IMC), vitamina D, vitamina B12, perímetro abdominal e relação cintura/estatura em três períodos: o pré-operatório de 1 a 6 meses, pós-operatório de 1 a 6 meses e pós-operatório de 1 a 2 anos. Resultados: Houve melhora em todos os parâmetros das análises clínicas. O IMC, no pré-operatório, teve a média dos valores de 39,8, no pré-operatório de 1 a 6 meses, os valores caíram para 33,2 e no pós-operatório de 1 ano média foi de 26. O perímetro abdominal teve média dos valores de 118,5, no pré-operatório, 105,2 no pós-operatório de 1 a 6 meses e 90,3 no pós-operatório de 1 a 2 anos. A relação cintura/estatura teve 0,73, 0,65 e 0,56 no pré, pós 1 a 6 meses e 1 a 2 anos respectivamente. Conclusão: O bypass gástrico em Y-de-Roux melhora a síndrome metabólica e a relação cintura/estatura é superior ao IMC na avaliação do perfil do risco cardiometabólico.

ABSTRACT Background: The increased prevalence of obesity has led to a significant increase in the occurrence of metabolic syndrome, a recognized risk factor for increased morbidity and mortality from cardiovascular diseases. Hyperglycemia or type 2 diabetes mellitus, dyslipidemia and arterial hypertension are its main components. Since 2015, international guidelines have recognized the benefits of bariatric surgery in each isolated factor of this syndrome. Aim: To evaluate the impact of Roux-en-Y gastric bypass in this syndrome comparing pre- and postoperative periods with laboratory analysis and to compare waist/height ratio and BMI in relation to the determination of the cardiometabolic risk profile. Methods: A retrospective study was carried out, selecting 80 patients undergoing Roux-en-Y gastric bypass. Total cholesterol, HDL, LDL, triglycerides, fasting glucose, glycated hemoglobin, insulin, body mass index (BMI), vitamin D, vitamin B12, waist circumference and waist/height ratio in three periods were analyzed: the preoperative period from 1 to 6 months, postoperative from 1 to 6 months and postoperative from 1 to 2 years. Results: There was an improvement in all parameters of the clinical analyses. The preoperative BMI had a mean value of 39.8, in the preoperative period from 1 to 6 months, the values dropped to 33.2 and in the postoperative period of 1 year, the mean was 26. The perimeter mean values of 118.5 preoperatively, 105.2 postoperatively from 1 to 6 months and 90.3 postoperatively from 1 to 2 years. Waist/height ratio was 0.73, 0.65 and 0.56 in pre, post 1 to 6 months and 1 to 2 years respectively. Conclusion: Roux-en-Y gastric bypass improves metabolic syndrome and waist-to-height ratio is superior to BMI in the assessment of the cardiometabolic risk profile.

Objective: Obstacles for computational tools in psychiatry include gathering robust evidence and keeping implementation costs reasonable. We report a systematic review of automated speech evaluation for the psychosis spectrum and analyze the value of information for a screening program in a healthcare system with a limited number of psychiatrists (Maputo, Mozambique). Methods: Original studies on speech analysis for forecasting of conversion in individuals at clinical high risk (CHR) for psychosis, diagnosis of manifested psychotic disorder, and first-episode psychosis (FEP) were included in this review. Studies addressing non-verbal components of speech (e.g., pitch, tone) were excluded. Results: Of 168 works identified, 28 original studies were included. Valuable speech features included direct measures (e.g., relative word counting) and mathematical embeddings (e.g.: word-to-vector, graphs). Accuracy estimates reported for schizophrenia diagnosis and CHR conversion ranged from 71 to 100% across studies. Studies used structured interviews, directed tasks, or prompted free speech. Directed-task protocols were faster while seemingly maintaining performance. The expected value of perfect information is USD 9.34 million. Imperfect tests would nevertheless yield high value. Conclusion: Accuracy for screening and diagnosis was high. Larger studies are needed to enhance precision of classificatory estimates. Automated analysis presents itself as a feasible, low-cost method which should be especially useful for regions in which the physician pool is insufficient to meet demand.

Objective: Population neuroscience is an emerging field that combines epidemiology and neuroscience to study how genes and the environment shape typical and atypical brain functioning. The objective of this study was to review key studies on population neuroscience from low- and middle-income countries (LMICs) and to identify potential gaps vis-à-vis studies conducted in high-income countries. Methods: We conducted a systematic review to search for longitudinal cohort studies investigating the development of psychiatric disorders in children and adolescents in LMICs. We performed an electronic search in the EMBASE and MEDLINE databases from inception to July 5th, 2019. Results: We found six cohorts from four countries that met our search criteria: three cohorts from Brazil, one from China, one from South Africa, and one from Mauritius. Relevant examples of findings from these studies are reported. Conclusion: Our results demonstrate the impact of the valuable science output these cohort designs promote, allowing LMICs to have a share in frontline global psychiatry research. National and international funding agencies should invest in LMIC population neuroscience in order to promote replication and generalization of research from high-income countries.