Treatment resistance in schizophrenia: a meta-analysis of prevalence and correlates

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.

Social cognition in individuals with schizophrenia, autism spectrum disorder and controls / Cognição social em indivíduos saudáveis, com esquizofrenia e com transtorno do espectro do autismo

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.

Identifying Depression Early in Adolescence: assessing the performance of a risk score for future onset of depression in an independent Brazilian sample

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.

Translation and cross-cultural adaptation to Brazilian Portuguese of two brief screening tools for youth at risk of psychosis: the Prodromal Questionnaire (PQ-16) and the PRIME-Screen

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.

Clozapine prescription trends in Brazil in the last decade

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.

Predictors of gaming disorder in children and adolescents: a school-based study

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.

Lowering costs for large-scale screening in psychosis: a systematic review and meta-analysis of performance and value of information for speech-based psychiatric evaluation

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.

Population neuroscience: challenges and opportunities for psychiatric research in low- and middle-income countries

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.

Schneider's first-rank symptoms as predictors of remission in antipsychotic-naive first-episode psychosis

Objective: German psychiatrist Kurt Schneider proposed the concept of first-rank symptoms (FRS) of schizophrenia in 1959. However, their relevance for diagnosis and prediction of treatment response are still unclear. Most studies have investigated FRS in chronic or medicated patients. The present study sought to evaluate whether FRS predict remission, response, or improvement in functionality in antipsychotic-naive first-episode psychosis. Methods: Follow-up study of 100 patients at first episode of psychosis (FEP), with no previous treatment, assessed at baseline and after 2 months of treatment. The participants were evaluated with the standardized Positive and Negative Syndrome Scale (PANSS) and Global Assessment of Functioning (GAF) and for presence of FRS. Results: Logistic regression analysis showed that, in this sample, up to three individual FRS predicted remission: voices arguing, voices commenting on one's actions, and thought broadcasting. Conclusion: Specific FRS may predict remission after treatment in FEP patients. This finding could give new importance to Kurt Schneider's classic work by contributing to future updates of diagnostic protocols and improving estimation of prognosis.

A 10-year ecological study of the methods of suicide used by Brazilian adolescents / Estudo ecológico de 10 anos sobre os métodos de suicídio usados por adolescentes brasileiros / Estudio ecológico abarcando 10 años sobre los métodos de suicidio practicados por adolescentes brasileños

Abstract: Suicide among adolescents has become a major public health problem worldwide. Our study sought to describe the most commonly used methods of suicide among adolescents aged 10 to 19 years in Brazil between 2006 and 2015. Complete data were obtained from the Brazilian Health Informatics Department (DATASUS) and coded into seven categories of suicide methods. The following statistical analyzes were performed: chi-square (χ2) tests to examine the association between the frequency of each suicide method and the year; odds ratios (OR) and 95% confidence intervals (95%CI) compared the relative chances of each suicide method occurring between boys and girls. In total, 8,026 suicides among Brazilian adolescents were registered over the analyzed period. The most commonly used method of suicide by both sexes was hanging (2015 = 70.3%), and the most significant increase was observed in girls (2015 = 65.82%). The proportional use of arms (2006 = 14.2%; 2015 = 9.1%) and poisoning (2006 = 13.3%; 2015 = 9.2%) decreased over the period. The increase in hanging is worrisome, mostly due to difficulties to impose access barriers and to its high lethality. In such context, a comprehensive understanding of suicide behaviors among adolescents in Brazil should be drawn to inform general prevention measures and, more specifically, the reasons for the increase in hanging need to be further investigated.

Resumo: O suicídio entre adolescentes é um importante problema de saúde pública em nível global. O estudo teve como principal objetivo descrever os métodos de suicídio mais usados por adolescentes brasileiros entre 10 e 19 anos de idade, de 2006 a 2015. Foram obtidos dados completos do Departamento de Informática do SUS (DATASUS), codificados em sete categorias de métodos de suicídio. As seguintes análises estatísticas foram realizadas: testes de qui-quadrado (χ2) para examinar a associação entre a frequência de cada método de suicídio e o ano do óbito. As razões de chances (OR) e intervalos de 95% de confiança (IC95%) compararam as chances relativas entre homens e mulheres para cada método de suicídio. Durante o período analisado, houve 8.026 suicídios entre adolescentes. O enforcamento foi o método de suicídio mais usado em ambos os sexos eram (2015 = 70,3%), com um aumento mais agudo em mulheres (2015 = 65,82%). O uso proporcional de armas (2006 = 14,2%; 2015 = 9,1%) e envenenamento (2006 = 13,3%; 2015 = 9,2%) diminuiu ao longo do período. O aumento dos enforcamentos é preocupante, suscitando questões com dificuldades na imposição de barreiras de acesso e a alta letalidade desse método. Nesse contexto, precisa haver uma compreensão mais abrangente dos comportamentos suicidas entre os adolescentes brasileiros para informar as medidas preventivas em geral e, mais especificamente, para elucidar os motivos para o aumento dos suicídios por enforcamento.

Resumen: El suicidio entre adolescentes se ha convertido en un importante problema de salud pública en todo el mundo. El objetivo de este estudio fue describir los métodos de suicido usados más comúnmente entre adolescentes, con edades comprendidas entre los 10 y 19 años, en Brasil desde 2006 hasta 2015. Los datos completos se obtuvieron del Departamento de Informática del Sistema Único de Salud (DATASUS) y se codificaron en siete categorías de métodos de suicidio. Se realizaron análisis estadísticos: tests chi-cuadrado (χ2) para examinar la asociación entre la frecuencia de cada método de suicidio y año. Odds ratios (OR) y los intervalos del 95% de confianza (IC95%) compararon las oportunidades relativas de cada método suicidio que se produce entre hombres y mujeres. Se registraron 8.026 suicidios entre adolescentes brasileños durante el período analizado. El método de suicidio más comúnmente usado por ambos sexos fue ahorcamiento (2015 = 70,3%), se observó un aumento más pronunciado en mujeres (2015 = 65,82%). El uso proporcional de armas (2006 = 14,2%; 2015 = 9,1%) y envenenamiento (2006 = 13,3%; 2015 = 9,2%) descendió durante este período. El incremento por ahorcamiento es preocupante, principalmente, en lo que se refiere a las dificultades para imponer barreras de acceso, así como por su alta letalidad. En este contexto, se deberían describir más los comportamientos suicidas entre adolescentes en Brasil para comprenderlos mejor, con el fin de que se tomen medidas de prevención general y, más específicamente, se profundice en las razones del incremento de ahorcamientos.

The association between adolescent suicide rates and socioeconomic indicators in Brazil: a 10-year retrospective ecological study

Objective: To examine suicide rates among adolescents from six large cities in Brazil and to analyze the relationship between adolescent suicide rates and socioeconomic indicators between 2006 and 2015. Methods: Generalized estimating equation models were used to assess the impact of socioeconomic factors - including social inequality and unemployment rates - on adolescent suicide rates. Results: The rate of adolescent suicide increased by 24% over the course of the study period. Social inequality (assessed using the Gini index), was positively associated with overall adolescent suicide rates (β = 10.68; 95%CI = 2.32-19.05; p ≤ 0.012). After disaggregating the findings by age (10-14 and 15-19 years), social inequality was associated with suicide rate only for adolescents aged 15-19 years (β = 9.63; 95%CI = 2.31-16.96; p ≤ 0.005). Disaggregating these findings by sex, the association with economic variables became significant only among females. Males had a higher overall suicide rate than females, and the highest rate was observed in male adolescents aged 15-19 years. Higher levels of unemployment were associated with higher suicide rates. Conclusion: Our findings suggest that socioeconomic indicators, particularly unemployment and social inequality, are relevant social determinants of suicide in adolescence.

Component mechanisms of executive function in schizophrenia and their contribution to functional outcomes

Objective: In schizophrenia, scores reflecting deficits in different cognitive processes are strongly correlated, making it difficult to establish a solid relationship between different cognitive mechanisms and other features of this disorder. The objective of this study was to explore whether three frequently postulated executive functions (updating, shifting, and inhibition) could be compared between groups and considered independently in terms of their respective roles in functional outcome. Methods: This study relied on confirmatory factor analysis of schizophrenia patients (n=141) and healthy controls (n=119). The main analyses examined the degree to which three executive functions (updating, set-shifting, and inhibition) could be separated in schizophrenia and compared this model among groups. Structural equation modeling analysis was also performed to examine the extent to which executive function components contribute to functional outcome in schizophrenia. Results: Multiple-group confirmatory factor analysis with unconstrained model parameters indicated that the full three-factor model may fit the data in both groups (χ2 = 61.48, degrees of freedom = 34, p < 0.001, comparative fit index = 0.95; standardized root mean square residual = 0.037; root mean square error of approximation = 0.04; Akaike's information criteria = 169.49; normed fit index = 0.90), although there was also a good data fit for the patient group with a two-factor model. In the patient group, structural equation modeling suggested that shifting and (principally) updating were associated with the general measure of functional outcome (regression path coefficients: 0.34, p < 0.005; 0.39, p < 0.005, respectively), although when combined the mechanisms fail to contribute. Conclusion: This data suggests that the factor structure may be similar but not identical between groups, and both updating and shifting may play an important role in functional outcome in schizophrenia.

Diagnostic operationalization and phenomenological heterogeneity in psychiatry: the case of attention deficit hyperactivity disorder / Operacionalización diagnóstica y heterogeneidad fenomenológica en psiquiatría: el caso del trastorno por déficit de atención con hiperactividad

Abstract Introduction We assessed the impact of polythetic conceptualizations of mental disorders on the validity and reliability of psychiatric diagnosis, with a specific focus on two levels of heterogeneity: phenomenological and pathophysiological. Objective We investigated this issue using attention deficit hyperactivity disorder (ADHD) as an example. Method We examined individuals from two samples enriched for psychopathology (n = 1 255 children in Porto Alegre and 1 257 children in São Paulo, Brazil). We conducted a series of data analyses to investigate phenomenological heterogeneity, including confirmatory factor analysis. We also investigated pathophysiological heterogeneity using symptom-level regressions between ADHD symptoms and four neurocognitive processes consistently linked to ADHD (working memory, inhibitory control, intra-subject variability in reaction times, and temporal processing). Lastly, we assessed the performance of polythetic systems for reliability testing inter-rater and test-rest reliability of two well-known symptomatic scales. Results Among the 116 200 possible combinations of symptoms to achieve DSM symptomatic threshold for categorical ADHD diagnosis, we found 173 combinations in the two independent samples, and only four were replicated in both samples (2.3%). We also found that the number of ADHD symptoms is a poor indicator of variation in the general ADHD latent trait. Overall, symptoms did not have specific profiles of associations with any of the neurocognitive processes. Reliability analyses revealed that increasing the number of items augments overall reliability of measurements. Discussion and conclusion Our findings illustrate both potential benefits and problems inherent to the polythetic system for ADHD. Implications for the search of mechanisms underlying psychiatric disorders are discussed.

Resumen Antecedentes Evaluamos el impacto de las conceptualizaciones politécnicas de los trastornos mentales en la validez y la fiabilidad del diagnóstico psiquiátrico, con un enfoque específico en dos niveles de heterogeneidad: fenomenológico y fisiopatológico. Objetivos Investigamos este problema utilizando el trastorno por déficit de atención e hiperactividad (TDAH) como ejemplo. Método Examinamos individuos de dos muestras enriquecidas por psicopatología (n = 1 255 niños en Porto Alegre y 1 257 niños en São Paulo, Brasil). Llevamos a cabo una serie de análisis de datos para investigar la heterogeneidad fenomenológica, incluido el análisis factorial confirmatorio. También investigamos la heterogeneidad fisiopatológica utilizando regresiones al nivel de síntomas entre los síntomas del TDAH y cuatro procesos neurocognitivos consistentemente vinculados al TDAH (memoria de trabajo, control inhibitorio, variabilidad intrasujeto en tiempos de reacción y procesamiento temporal). Por último, evaluamos el rendimiento de los sistemas politéticos para la prueba de confiabilidad interevaluador y la confiabilidad test-rest de dos escalas sintomáticas bien conocidas. Resultados Entre las 116 200 posibles combinaciones de síntomas para alcanzar el umbral sintomático del DSM para el diagnóstico categórico de TDAH, encontramos 173 combinaciones en las dos muestras independientes y sólo cuatro se replicaron en ambas muestras (2.3%). También encontramos que la cantidad de síntomas de TDAH no es un buen indicador de la variación en el rasgo latente general del TDAH. En general, los síntomas no tenían perfiles específicos de asociaciones con ninguno de los procesos neurocognitivos. Los análisis de confiabilidad revelaron que aumentar el número de artículos aumenta la confiabilidad general de las mediciones. Discusión y conclusión Nuestros hallazgos ilustran tanto los beneficios potenciales como los problemas inherentes al sistema politécnico para el TDAH. Se discuten las implicaciones para la búsqueda de mecanismos subyacentes a los trastornos psiquiátricos.