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.

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.

The impact of inflammatory and metabolic markers on depression, anxiety, and cognition after COVID-19: A narrative review.

INTRODUCTION: There has been growing concern about the long-term effects of COVID-19 on mental health. The biological factors common to psychiatric conditions and COVID-19 are not yet fully understood. METHODOLOGY: We narratively reviewed prospective longitudinal studies that measured metabolic or inflammatory markers and assessed psychiatric sequalae and cognitive impairment in individuals with COVID-19 at least 3 months after the infection. A literature search identified three relevant cohort studies. RESULTS: Overall, depressive symptomatology and cognitive deficits persisted for up to one year after COVID-19; depression and cognitive changes were predicted by acute inflammatory markers, and changes in these markers correlated with changes in depressive symptomatology; female sex, obesity, and the presence of inflammatory markers were associated with more severe clusters of physical and mental health status in patients' self-perceived recovery; and plasma metabolic profiles of patients continued to differ from those of healthy controls three months after hospital discharge, which were associated with widespread alterations in neuroimaging, reflecting issues with white matter integrity. This is a non-systematic review and cautions should be made while interpreting the conclusions. CONCLUSION: In individuals affected by the COVID-19, prolonged exposure to stress and alterations in metabolic and inflammatory markers plays a central role in psychiatric sequalae and cognitive deficits in the long term.

What is the Best Latent Structure of Negative Symptoms in Schizophrenia? A Systematic Review.

BACKGROUND: Determining the best latent structure of negative symptoms in schizophrenia could benefit assessment tools, neurobiological research, and targeted interventions. However, no review systematically evaluated studies that assessed and validated latent models of negative symptoms. OBJECTIVE: To identify and evaluate existing latent structure models in the literature of negative symptoms and to determine the best model. METHOD: Systematic search of MEDLINE, EMBASE, and Scopus on July 19, 2020, for confirmatory factor analysis models of negative symptoms in patients with schizophrenia. The available evidence was assessed through 2 sets of criteria: (1) study design quality-based on negative symptoms assessment and modeling strategy and (2) psychometric quality and model fit-based on fit indices and factor definition quality. RESULTS: In total, 22 studies (n = 17 086) from 9 countries were included. Studies differed greatly regarding symptom scales, setting, and sample size (range = 86-6889). Dimensional models included 2-6 factors (median = 4). Twelve studies evaluated competing models and adopted appropriate instruments to assess the latent structure of negative symptoms. The 5-factor and hierarchical models outperformed unitary, 2-factor, and 3-factor models on all direct comparisons, and most of the analyses derived from the Brief Negative Symptom Scale. Considering the quality criteria proposed, 5-factor and hierarchical models achieved excellent fit in just one study. CONCLUSIONS: Our review points out that the 5-factor and hierarchical models represent the best latent structure of negative symptoms, but the immaturity of the relevant current literature may affect the robustness of this conclusion. Future studies should address current limitations regarding psychometric properties and also address biological and clinical validity to refine available models.

Prevalence and predictors of treatment-resistant schizophrenia in a tertiary hospital in Northeast Brazil.

OBJECTIVE: To investigate epidemiological factors related to treatment-resistant schizophrenia (TRS) in Northeast Brazil, a region where data about mental health are still scarce. METHODS: This retrospective cross-sectional study included all patients with schizophrenia currently receiving treatment at the outpatient psychiatric clinic of a tertiary hospital in Northeast Brazil. They were divided into TRS and treatment-responsive groups, and epidemiological characteristics of both groups were compared. A logistic regression model investigated factors related to treatment resistance. RESULTS: Two hundred and five patients were included, 155 treatment-resistant and 50 treatment-responsive. The TRS group had higher use of benzodiazepines (36.1 vs. 18%, p = 0.017) and antiepileptics (36.8 vs. 8.0%, p < 0.001), antipsychotic polypharmacy (28.6 vs. 8%, p = 0.003) and suicide attempts (35.6 vs. 20%, p = 0.04). Age at onset was younger (19.7±7.3 vs. 24.6±8.6 years, p = 0.001) and CGI was higher in TRS (3.72±1.00 vs. 3.16±1.00, p = 0.001). In logistic regression, being married was a protector (odds ratio [OR] = 0.248, 95% confidence interval [95%CI] 0.091-0.679, p = 0.007) and younger age at onset was a predictor (OR = 1.076, 95%CI 1.034-1.120, p < 0.001) of treatment resistance. CONCLUSION: Early onset of disease was associated with more treatment resistance, while being married with less resistance. Clinicians should identify early predictors of resistance in order to reduce unfavorable outcomes.

Implementation of early psychosis services in Latin America: A scoping review.

AIM: The evidence of the effectiveness and cost-effectiveness of early intervention for psychosis (EIP) services has motivated their implementation worldwide. However, complex interventions of such EIP services require local adaptations to successfully match population needs and cultural differences. Latin America is a heterogenous region where EIP services are progressively being adopted. Our aim is to map such initiatives in the region with a focus on implementation outcomes. METHODS: A scoping review following the Preferred Reporting Items for Systematic review and Meta-Analysis extension for Scoping Reviews guidelines was conducted. International and regional databases were searched for publications describing EIP programmes in the region. Besides mapping the services, we described implementation outcomes based on the Standards for Reporting Implementation Studies Checklist. RESULTS: Ten articles describing seven EIP initiatives from the region were found. Four countries were represented: Argentina, Brazil, Chile and Mexico. The implementation outcomes reporting was heterogenous, although it was possible to ascertain EIP services are feasible and adequate for the region's context. Also, there is some evidence of effectiveness in terms of reducing hospitalizations and improving symptoms. Information about fidelity measures was scarce and there was no information about costs or cost-effectiveness. CONCLUSIONS: Only a small proportion of Latin American countries have adopted EIP services. Although these programmes seem to be feasible and effective, data on other implementation outcomes, such as fidelity, cultural appropriateness, cost-effectiveness and affordability are not available. This might in part explain why this effective approach has not been yet scaled-up at nationwide levels.

A 10-year ecological study of the methods of suicide used by Brazilian adolescents.

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.

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.

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.

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.

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.

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.

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 (ß = 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 (ß = 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.

Ten-year evolution of suicide rates and economic indicators in large Brazilian urban centers.

PURPOSE OF REVIEW: This was a retrospective ecological study to examine the relationship between suicide rates and economic indicators in large Brazilian urban centers. Data on macroeconomic indicators (GDP and unemployment rates) and suicide rates of the largest Brazilian cities were collected from January 2006 to December 2015. RECENT FINDINGS: Six cities were included in the study: Porto Alegre in the South, Recife and Salvador in the Northeast, and Belo Horizonte, São Paulo and Rio de Janeiro in the Southeast region. We observed a 4% increase in the age-adjusted suicide rate in these large Brazilian urban centers from 2006 to 2015, which is less pronounced than the 9% increase in the national rates of suicide observed in the same period. SUMMARY: The effect of economic indicators was heterogeneous among the centers, but, overall, the variation in suicide rates was inversely related to unemployment and did not show a significant relationship with GDP. These findings indicate a more complex link between economics and suicide whenever looking at local regional indicators. Further research should focus on possible intervening factors, what may inform better preventive interventions.

Differences in community, hospital and intensive care unit-acquired acute kidney injury: observational study in a nephrology service of a developing country.

BACKGROUND: Acute kidney injury (AKI) complicates more than 7% of all in-hospital patients. The aim of this study is to investigate the differences in community, hospital and intensive care unit-acquired AKI in patients undergoing nephrology consultation in a tertiary hospital in a developing country. METHODS: An observational cohort study of all patients with AKI admitted to the General Hospital of Fortaleza, Brazil was conducted. RIFLE criteria were used to classify the patients and to assess their association with death. Univariate and multivariate analyses were performed to investigate the factors associated with death. RESULTS: Of 491 AKI patients undergoing nephrology consultation, the mean age was 55.2 ± 22.9 years. Community-acquired AKI was observed in 55% of cases, general ward-acquired in 29% and ICU-acquired in 15.3%. Late Nephrology consultation was observed, and the great majority of patients had "Failure" classification (90%) according to RIFLE criteria. Intermittent hemodialysis was required in 68% of cases. The overall in-hospital mortality was 23%. The in-hospital mortality was higher in ICU-acquired AKI (33.6%). Community acquired AKI had a higher mortality than general ward-acquired AKI (23% vs. 11.6%, p = 0.001). Risk factors for death were infection (OR = 2.0, p = 0.003), neoplasms (OR = 1.89, p = 0.042), community acquired-AKI (OR = 1.27, p = 0.003), ICU acquired-AKI (OR = 2.76, p < 0.0001) and need for renal replacement therapy (OR = 2.64, p < 0.001). CONCLUSIONS: AKI is a frequent and frequently fatal condition. Mortality was higher in community and ICU-acquired than hospital ward-acquired AKI.