Lifetime cannabis use and childhood trauma associated with CNR1 genetic variants increase the risk of psychosis: findings from the STREAM study.

BACKGROUND: Gene-environment interactions increase the risk of psychosis. Aim: To investigate gene-gene and gene-environment interactions in psychosis including single nucleotide variants (SNVs) of dopamine-2 receptor (D2R), N-methyl-d-aspartate receptor (NMDAR) and cannabinoid receptor type 1 (CB1R), lifetime cannabis use and childhood trauma. METHODS: Twenty-three SNVs of genes related to D2R (DRD2: rs1799978, rs7131056, rs6275), NMDAR (GRIN1: rs4880213, rs11146020; GRIN2A: rs1420040, rs11866328; GRIN2B: rs890, rs2098469, rs7298664), and CB1R genes (CNR1: rs806380, rs806379, rs1049353, rs6454674, rs1535255, rs2023239, rs12720071, rs6928499, rs806374, rs7766029, rs806378, rs10485170, rs9450898) were genotyped in 143 first-episode psychosis patients (FEPp) and 286 community-based controls by Illumina HumanCoreExome-24 BeadChip. Associations between gene-gene and gene-environment were performed using nonparametric multifactor dimensionality reduction software. RESULTS: Single locus analysis among the 23 SNVs with psychosis and gene-gene interactions were not significant (p>0.05 for all comparisons); however, both environmental risk factors showed an association with psychosis (p<0.001). Moreover, gene-environment interactions were significant for SNV in CNR1 and cannabis use. The best performing model was the combination between CNR1 rs12720071 and lifetime cannabis use (p<0.001) suggesting an increased risk of psychosis. CONCLUSION: Our study supports the hypothesis of gene-environment interactions for psychosis involving the T allele carriers of CNR1 SNVs, childhood trauma and cannabis use in psychosis.n.

Increased blood neutrophil extracellular traps (NETs) associated with early life stress: translational findings in recent-onset schizophrenia and rodent model.

Higher levels of interleukin (IL)-6 and elevated neutrophil counts are consistently reported in the blood of patients with schizophrenia. Stressors during childhood and/or adolescence are major socioenvironmental risk factors for schizophrenia and may contribute to immune dysregulation. Previous studies using blood cytokines to stratify patients with schizophrenia suggest that only a subset presents a low-grade inflammatory state. However, these studies have not addressed whether environmental factors such as childhood maltreatment contributed to identifying inflammatory clusters. Moreover, a neutrophil-related mechanism (Neutrophil Extracellular Traps; NETs) central to both the initiation and chronicity of autoimmune and inflammatory diseases has never been investigated in psychiatry. Elevated NETs in schizophrenia may predispose patients to inflammatory and autoimmune diseases resulting in reduced life expectancy. We, therefore, investigated NETs as a novel mechanism and biological target in early schizophrenia and their role together with IL-6 and childhood maltreatment in identifying cluster subgroups. We found increased NETs in the plasma of patients with early schizophrenia (n = 78) compared to both their unaffected siblings (n = 25) and community controls (n = 78), irrespective of sex, body mass index, psychoactive drug use, or tobacco smoking. Increased NETs in patients were unrelated to antipsychotic treatment, which was further tested in vitro using fresh neutrophils. By applying unsupervised two-step clustering analysis, we integrated values of NETs, IL-6, and childhood maltreatment scores. We identified two main clusters; childhood maltreatment scores and NETs were the most important variables contributing to cluster separation (high-CL1 and low-CL2), while IL-6 was the least contributor. Patients allocated in the high-CL1 (61.5%) had significantly higher childhood maltreatment scores, NETs, and IL-6 levels than the remaining groups (patients low-CL2, siblings, and controls high-CL1 and low-CL2). We complemented these findings with a rat model based on stress exposure during adolescence that results in several schizophrenia-like changes in adulthood. We found that adolescent stressed rats had higher NETs and IL-6 levels in serum compared to non-stressed rats with a tendency to produce more NETs from the bone marrow. Altogether, this study brings a novel cellular-based mechanism in schizophrenia that, combined with early-stress, could be useful to identify subgroups for more personalised treatments.

The role of religiosity and spirituality in interpersonal violence: a systematic review and meta-analysis.

OBJECTIVE: Religiosity and spirituality (R/S) have been negatively associated with several mental health problems, including delinquency. The study aimed to investigate the relationship between R/S and interpersonal violence using a systematic review. METHODS: We carried out a descriptive systematic review followed by meta-analyses using seven different databases. We included observational studies that assessed the relationship between R/S and different types of interpersonal violence (physical and sexual aggression, and domestic violence). RESULTS: A total of 16 599 articles were screened in the databases and, after applying the eligibility criteria, 67 studies were included in the systematic review, and 43 in the meta-analysis. Results showed that higher levels of R/S were significantly associated with decreased physical and sexual aggression, but not domestic violence. All selected studies evidenced sufficient methodological quality based on the assessment criteria, and 26.8% of them were cohort studies. In the sub-analyses, the role of R/S was more prevalent among adolescents. CONCLUSION: There is an inverse relationship between R/S and physical and sexual aggression, suggesting a protective role. However, these results were not observed for domestic violence. Healthcare professionals and managers should be aware of their patients' beliefs when investigating interpersonal violence to create tailored interventions for reducing violent behavior.

Participants' and Nurses' Experiences With a Digital Intervention for Patients With Depressive Symptoms and Comorbid Hypertension or Diabetes in Peru: Qualitative Post-Randomized Controlled Trial Study.

BACKGROUND: Depression is one of the most prevalent mental disorders and a leading cause of disability, disproportionately affecting specific groups, such as patients with noncommunicable diseases. Over the past decade, digital interventions have been developed to provide treatment for these patients. CONEMO (Emotional Control in Spanish) is an 18-session psychoeducational digital intervention delivered through a smartphone app and minimally supported by a nurse. CONEMO demonstrated effectiveness in reducing depressive symptoms through a randomized controlled trial (RCT) among patients with diabetes, hypertension, or both, in Lima, Peru. However, in addition to clinical outcomes, it is important to explore users' experiences, satisfaction, and perceptions of usability and acceptability, which can affect their engagement with the intervention. OBJECTIVE: This study aimed to explore the RCT participants' experiences with CONEMO in Peru, complemented with information provided by the nurses who monitored them. METHODS: In 2018, semistructured interviews were conducted with a sample of 29 (13.4%) patients from the 217 patients who participated in the CONEMO intervention in Peru and the 3 hired nurses who supported its delivery. Interviewees were selected at random based on their adherence to the digital intervention (0-5, 10-14, and 15-18 sessions completed), to include different points of view. Content analysis was conducted to analyze the interviews. RESULTS: Participants' mean age was 64.4 (SD 8.5) years, and 79% (23/29) of them were women. Most of the interviewed participants (21/29, 72%) stated that CONEMO fulfilled their expectations and identified positive changes in their physical and mental health after using it. Some of these improvements were related to their thoughts and feelings (eg, think differently, be more optimistic, and feel calmer), whereas others were related to their routines (eg, go out more and improve health-related habits). Most participants (19/29, 66%) reported not having previous experience with using smartphones, and despite experiencing some initial difficulties, they managed to use CONEMO. The most valued features of the app were the videos and activities proposed for the participant to perform. Most participants (27/29, 93%) had a good opinion about the study nurses and reported feeling supported by them. A few participants provided suggestions to improve the intervention, which included adding more videos, making the sessions' text simple, extending the length of the intervention, and improving the training session with long explanations. CONCLUSIONS: The findings of this qualitative study provide further support and contextualize the positive results found in the CONEMO RCT, including insights into the key features that made the intervention effective and engaging. The participants' experience with the smartphone and CONEMO app reveal that it is feasible to be used by people with little knowledge of technology. In addition, the study identified suggestions to improve the CONEMO intervention for its future scale-up. TRIAL REGISTRATION: ClinicalTrials.gov NCT03026426; https://clinicaltrials.gov/ct2/show/NCT03026426.

Justiça organizacional e doença cardiometabólica: uma revisão sistemática / Organizational justice and cardiometabolic disease: a systematic review

Resumo Os efeitos da justiça organizacional sobre a saúde dos trabalhadores têm sido investigados em diversas áreas de trabalho. Entretanto, a sistematização da informação disponível sobre os efeitos relacionados às doenças cardiovasculares (DCV) e à diabetes é escassa. O objetivo deste artigo é revisar sistematicamente a associação entre justiça organizacional e DCV e metabólica em trabalhadores adultos. A estratégia de busca incluiu os termos justiça organizacional, doença coronariana, doença cerebrovascular, hipertensão arterial sistêmica, diabetes mellitus e DCV. As bases de dados investigadas foram MEDLINE, EMBASE e LILACS. A qualidade dos estudos foi avaliada pelo instrumento desenvolvido pelo National Institute of Health. Foram identificados 1.959 títulos. Após avaliação, foram selecionados oito estudos. Os indivíduos com percepção de justiça organizacional alta apresentaram menor risco de DCV e metabólica. Baixa justiça organizacional tem repercussões para a saúde cardiovascular e metabólica dos trabalhadores. A elaboração de estratégias para promover justiça organizacional deve ser priorizada para assim mitigar seus impactos para os trabalhadores e as instituições.

Abstract The effects of organizational justice on workers' health have been investigated in several areas of work. However, the systematization of available information on the effects related to cardiovascular diseases (CVD) and diabetes is scarce. This article aims to systematically review the association between organizational justice and CVD and metabolic disease in adult workers. The search strategy included the terms organizational justice, coronary heart disease, cerebrovascular disease, systemic arterial hypertension, diabetes mellitus and CVD. This study investigated the following databases: MEDLINE, EMBASE, and LILACS. The quality of the studies was assessed using the instrument developed by the National Institute of Health. Results: This study identified 1,959 titles. After evaluation, eight studies were selected. Individuals with a high perception of organizational justice showed a lower risk of CVD and metabolic disease, whereas low organizational justice presented repercussions for the cardiovascular and metabolic health of workers. The development of strategies to promote organizational justice must be prioritized and thus mitigate its impacts on workers and institutions.

Organizational justice and cardiometabolic disease: a systematic review. / Justiça organizacional e doença cardiometabólica: uma revisão sistemática.

The effects of organizational justice on workers' health have been investigated in several areas of work. However, the systematization of available information on the effects related to cardiovascular diseases (CVD) and diabetes is scarce. This article aims to systematically review the association between organizational justice and CVD and metabolic disease in adult workers. The search strategy included the terms organizational justice, coronary heart disease, cerebrovascular disease, systemic arterial hypertension, diabetes mellitus and CVD. This study investigated the following databases: MEDLINE, EMBASE, and LILACS. The quality of the studies was assessed using the instrument developed by the National Institute of Health. Results: This study identified 1,959 titles. After evaluation, eight studies were selected. Individuals with a high perception of organizational justice showed a lower risk of CVD and metabolic disease, whereas low organizational justice presented repercussions for the cardiovascular and metabolic health of workers. The development of strategies to promote organizational justice must be prioritized and thus mitigate its impacts on workers and institutions.

Os efeitos da justiça organizacional sobre a saúde dos trabalhadores têm sido investigados em diversas áreas de trabalho. Entretanto, a sistematização da informação disponível sobre os efeitos relacionados às doenças cardiovasculares (DCV) e à diabetes é escassa. O objetivo deste artigo é revisar sistematicamente a associação entre justiça organizacional e DCV e metabólica em trabalhadores adultos. A estratégia de busca incluiu os termos justiça organizacional, doença coronariana, doença cerebrovascular, hipertensão arterial sistêmica, diabetes mellitus e DCV. As bases de dados investigadas foram MEDLINE, EMBASE e LILACS. A qualidade dos estudos foi avaliada pelo instrumento desenvolvido pelo National Institute of Health. Foram identificados 1.959 títulos. Após avaliação, foram selecionados oito estudos. Os indivíduos com percepção de justiça organizacional alta apresentaram menor risco de DCV e metabólica. Baixa justiça organizacional tem repercussões para a saúde cardiovascular e metabólica dos trabalhadores. A elaboração de estratégias para promover justiça organizacional deve ser priorizada para assim mitigar seus impactos para os trabalhadores e as instituições.

Excess mortality in a cohort of Brazilian patients with a median follow-up of 11 years after the first psychiatric hospital admission.

PURPOSE: To estimate the mortality rates of a cohort of Brazilian patients after their first psychiatric admission and determine the possible risk factors associated with excess mortality. METHODS: The study included a cohort of psychiatric patients hospitalised from Jan 1, 2002 to Dec 31, 2007 in the catchment area of Ribeirão Preto, São Paulo state, Brazil. Data were linked to deaths that occurred between Jan 1, 2002 and Dec 31, 2016 from the SEADE Foundation (state data analysis system of São Paulo). The mortality rate (MR), age-sex-standardised mortality ratio (SMR), life expectancy at birth, and years of life lost (YLL) were computed. The factors associated with mortality were analysed by survival analysis using a Cox proportional hazards regression model. RESULTS: Of 4019 patients admitted (54.76% male), 803 died (69.74% male) during the follow-up (median = 11.25 years). Mortality rates were approximately three-fold higher than expected (SMR = 2.90, 95% CI 2.71-3.11). The highest mortality rate was noted in men with alcohol-related disorders (SMR = 5.50, 95% CI 4.87-6.19). Male sex (adjusted hazard ratio (aHR) = 1.62, 95% CI 1.37-1.92), higher age (aHR = 21.47, 95% CI 13.48-34.17), and unemployment (aHR = 1.22, 95% CI 1.05-1.43) significantly increased the mortality risk from all causes. The average YLL was 27.64 years with the highest YLL noted in nonalcohol substance-related disorders (39.22 years). The life expectancy at birth in this cohort was 47.27 years. Unnatural causes of death were associated with nonwhite skin colour and substance-related disorders. CONCLUSION: An excess of mortality and a significant reduction in life expectancy of mentally disordered patients who were first admitted to psychiatric beds was noted, particularly patients admitted for substance-related disorders, which should represent a priority in mental health policies.

Trend in the prevalence of depressive symptoms in Brazil: results from the Brazilian National Health Survey 2013 and 2019.

This study aims to evaluate national variation in depression prevalence and in different sociodemographic groups, health behaviors, and macroregions of Brazil from 2013 to 2019. Data were obtained from two nationwide Brazilian surveys - Brazilian National Health Survey 2013 and 2019. Participants aged 18 years or older were included, totaling 60,202 individuals in 2013 and 88,531 in 2019. Depression was evaluated with the Patient Health Questionnaire-9 (PHQ-9). All estimations accounted for the population weights and the complex sampling. The findings showed that during the six years between the two surveys, the prevalence of depression in Brazil increased by 36.7%, going from 7.9% in 2013 to 10.8% in 2019, and this increase is higher among unemployed young adults, aged 18 to 24 years, with the increase in the prevalence of depression almost tripled (3.7 in 2013 and 10.3 in 2019), an increase of 178.4%. Those dwelling in urban areas had a higher increase in the prevalence of depression in the six-year period (39.8%) when compared to residents in rural areas (20.2%). There was an increase in the prevalence of depression from 2013 to 2019 for the worst categories of the three health behaviors included in the study for both men and women: heavy drinking, smoking, and not exercising the recommended level of physical activity. Our results show a significant increase in the prevalence of depression over the six years between the two surveys, mainly among the younger and unemployed men. The country's economic recession during this period may explain these findings.

Childhood Maltreatment, Educational Attainment, and IQ: Findings From a Multicentric Case-control Study of First-episode Psychosis (EU-GEI).

BACKGROUND AND HYPOTHESIS: Evidence suggests that childhood maltreatment (ie, childhood abuse and childhood neglect) affects educational attainment and cognition. However, the association between childhood maltreatment and Intelligence Quotient (IQ) seems stronger among controls compared to people with psychosis. We hypothesised that: the association between childhood maltreatment and poor cognition would be stronger among community controls than among people with first-episode of psychosis (FEP); compared to abuse, neglect would show stronger associations with educational attainment and cognition; the association between childhood maltreatment and IQ would be partially accounted for by other risk factors; and the association between childhood maltreatment, educational attainment, and IQ would be stronger among patients with affective psychoses compared to those with nonaffective psychoses. STUDY DESIGN: 829 patients with FEP and 1283 community controls from 16 EU-GEI sites were assessed for child maltreatment, education attainment, and IQ. STUDY RESULTS: In both the FEP and control group, childhood maltreatment was associated with lower educational attainment. The association between childhood maltreatment and lower IQ was robust to adjustment for confounders only among controls. Whereas childhood neglect was consistently associated with lower attainment and IQ in both groups, childhood abuse was associated with IQ only in controls. Among both patients with affective and nonaffective psychoses, negative associations between childhood maltreatment and educational attainment were observed, but the crude association with IQ was only evident in affective psychoses. CONCLUSIONS: Our findings underscore the role of childhood maltreatment in shaping academic outcomes and cognition of people with FEP as well as controls.

Early Schizophrenia and Bipolar Disorder Patients Display Reduced Neural Prepulse Inhibition.

BACKGROUND: Altered sensorimotor gating has been demonstrated by Prepulse Inhibition (PPI) tests in patients with psychosis. Recent advances in signal processing methods allow assessment of neural PPI through electroencephalogram (EEG) recording during acoustic startle response measures (classic muscular PPI). Simultaneous measurements of muscular (eye-blink) and neural gating phenomena during PPI test may help to better understand sensorial processing dysfunctions in psychosis. In this study, we aimed to assess simultaneously muscular and neural PPI in early bipolar disorder and schizophrenia patients. METHOD: Participants were recruited from a population-based case-control study of first episode psychosis. PPI was measured using electromyography (EMG) and EEG in pulse alone and prepulse + pulse with intervals of 30, 60, and 120 ms in early bipolar disorder (n = 18) and schizophrenia (n = 11) patients. As control group, 15 socio-economically matched healthy subjects were recruited. All subjects were evaluated with Rating Scale, Hamilton Rating Scale for Depression, and Young Mania Rating Scale questionnaires at recruitment and just before PPI test. Wilcoxon ranked sum tests were used to compare PPI test results between groups. RESULTS: In comparison to healthy participants, neural PPI was significantly reduced in PPI 30 and PPI60 among bipolar and schizophrenia patients, while muscular PPI was reduced in PPI60 and PPI120 intervals only among patients with schizophrenia. CONCLUSION: The combination of muscular and neural PPI evaluations suggested distinct impairment patterns among schizophrenia and bipolar disorder patients. Simultaneous recording may contribute with novel information in sensory gating investigations.

Immunogenicity and safety of two doses of the CoronaVac SARS-CoV-2 vaccine in SARS-CoV-2 seropositive and seronegative patients with autoimmune rheumatic diseases in Brazil: a subgroup analysis of a phase 4 prospective study.

BACKGROUND: We aimed to examine the immunogenicity pattern induced by the inactivated SARS-CoV-2 vaccine CoronaVac (Sinovac Life Sciences, Beijing, China) in SARS-CoV-2 seropositive patients with autoimmune rheumatic diseases compared with seropositive controls, seronegative patients with autoimmune rheumatic diseases, and seronegative controls. METHODS: CoronavRheum is an ongoing, prospective, controlled, phase 4 study, in which patients aged 18 years or older with autoimmune rheumatic diseases, and healthy controls were recruited from a single site (Rheumatology Division of Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo) in São Paulo, Brazil Participants were vaccinated with two doses of CoronaVac (intramuscular injection, 3 µg in 0·5 mL of ß-propiolactone inactivated SARS-CoV-2) on day 0 and on day 28. Blood samples were taken pre-vaccination on day 0, day 28, and also on day 69. For this subgroup analysis, participants were defined as being SARS-CoV-2 seropositive or seronegative prevaccination via anti-SARS-CoV-2 spike (S)1 or S2 IgG (cutoff of 15·0 arbitrary units [AU] per mL) or neutralising antibody titres (cutoff of ≥30%) and were matched for age and sex, via convenience sampling, in a 1:3:1:1 ratio (seropositive patients to seronegative patients to seropositive controls to seronegative controls). The primary outcomes were rates of anti-SARS-CoV-2 S1 and S2 IgG seropositivity and SARS-CoV-2 neutralising antibody positivity at day 28 and day 69 and immunogenicity dynamics assessed by geometric mean titres (GMTs) of IgG and median neutralising activity in seropositive patients with autoimmune rheumatic diseases compared with seronegative patients and seropositive and seronegative controls. We assessed safety in all participants randomly selected for this subgroup analysis. This study is registered with ClinicalTrials.gov, NCT04754698, and is ongoing for long-term immunogenicity evaluation. FINDINGS: Between Feb 4 and Feb 8, 2021, 1418 patients and 542 controls were recruited, of whom 1685 received two vaccinations (1193 patients and 492 controls). After random sampling, our immunogenicity analysis population comprised 942 participants, of whom 157 were SARS-CoV-2 seropositive patients with autoimmune rheumatic diseases, 157 were seropositive controls, 471 were seronegative patients, and 157 were seronegative controls; the median age was 48 years (IQR 38-56) and 594 (63%) were female and 348 (37%) were male. For seropositive patients and controls, an increase in anti-SARS-CoV-2 S1 and S2 IgG titres (seropositive patients GMT 52·3 [95% CI 42·9-63·9] at day 0 vs 128·9 [105·6-157·4] at day 28; seropositive controls 53·3 [45·4-62·5] at day 0 vs 202·0 [174·8-233·4] at day 28) and neutralising antibody activity (seropositive patients 59% [IQR 39-83] at day 0 vs 82% [54-96] at day 28; seropositive controls 58% [41-79] at day 0 vs 92% [79-96] at day 28), was observed from day 0 to day 28, without further increases from day 28 to day 69 (at day 69 seropositive patients' GMT was 137·1 [116·2-161·9] and neutralising antibody activity was 79% [57-94]); and seropositive controls' GMT was 188·6 [167·4-212·6] and neutralising antibody activity was 92% [75-96]). By contrast, for seronegative patients and controls, the second dose was required for maximum response at day 69, which was lower in seronegative patients than in seronegative controls. GMTs in seronegative patients were 2·3 (95% CI 2·2-2·3) at day 0, 5·7 (5·1-6·4) at day 28, and 29·6 (26·4-33·3) at day 69, and in seronegative controls were 2·3 (2·1-2·5) at day 0, 10·6 (8·7-13·1) at day 28, and 71·7 (63·5-81·0) at day 69; neutralising antibody activity in seronegative patients was 15% (IQR 15-15) on day 0, 15% (15-15) at day 28, and 39% (15-65) at day 69, and in seronegative controls was 15% (15-15) at day 0, 24% (15-37) at day 28, and 61% (37-79) at day 69. Neither seronegative patients nor seronegative controls reached the GMT or antibody activity levels of seropositive patients at day 69. INTERPRETATION: By contrast with seronegative patients with autoimmune rheumatic diseases, seropositive patients have a robust response after a single dose of CoronaVac. Our findings raise the possibility that the reduced immunogenicity observed in seronegative patients might not be the optimum response potential to SARS-CoV-2 vaccination, and therefore emphasise the importance of at least a single booster vaccination in these patients. FUNDING: Fundação de Amparo à Pesquisa do Estado de São Paulo, Conselho Nacional de Desenvolvimento Científico e Tecnológico, and B3-Bolsa de Valores do Brasil. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Trend in the prevalence of depressive symptoms in Brazil: results from the Brazilian National Health Survey 2013 and 2019 / Tendência na prevalência de sintomas depressivos no Brasil: resultados da Pesquisa Nacional de Saúde, 2013 e 2019 / Tendencia en la prevalencia de síntomas depresivos en Brasil: resultados de las Encuesta Nacional de Salud de 2013 y 2019

This study aims to evaluate national variation in depression prevalence and in different sociodemographic groups, health behaviors, and macroregions of Brazil from 2013 to 2019. Data were obtained from two nationwide Brazilian surveys - Brazilian National Health Survey 2013 and 2019. Participants aged 18 years or older were included, totaling 60,202 individuals in 2013 and 88,531 in 2019. Depression was evaluated with the Patient Health Questionnaire-9 (PHQ-9). All estimations accounted for the population weights and the complex sampling. The findings showed that during the six years between the two surveys, the prevalence of depression in Brazil increased by 36.7%, going from 7.9% in 2013 to 10.8% in 2019, and this increase is higher among unemployed young adults, aged 18 to 24 years, with the increase in the prevalence of depression almost tripled (3.7 in 2013 and 10.3 in 2019), an increase of 178.4%. Those dwelling in urban areas had a higher increase in the prevalence of depression in the six-year period (39.8%) when compared to residents in rural areas (20.2%). There was an increase in the prevalence of depression from 2013 to 2019 for the worst categories of the three health behaviors included in the study for both men and women: heavy drinking, smoking, and not exercising the recommended level of physical activity. Our results show a significant increase in the prevalence of depression over the six years between the two surveys, mainly among the younger and unemployed men. The country's economic recession during this period may explain these findings.

O estudo objetiva avaliar a variação nacional na prevalência geral da depressão e em diferentes grupos sociodemográficos, comportamentos de saúde e macrorregiões do Brasil entre 2013 e 2019. Os dados foram obtidos de dois inquéritos brasileiros de abrangência nacional, a Pesquisa Nacional de Saúde (PNS) 2013 e a 2019. Entre os participantes com idade de 18 anos ou mais, houve 60.202 indivíduos em 2013 e 88.531 em 2019. A depressão foi avaliada com o Questionário de Saúde do Paciente-9 (PHQ-9). Todas as estimativas levaram em conta os pesos populacionais e a amostragem complexa. Os achados mostraram que durante os seis anos entre as duas edições da PNS, a prevalência de depressão no Brasil aumentou em 36,7%, de 7,9% em 2013 para 10,8% em 2019, com um aumento ainda maior em adultos jovens, no grupo etário de 18 a 24 anos, e naqueles que não estavam trabalhando, onde houve um aumento de quase três vezes na prevalência de depressão (3,7% em 2013 e 10,3% em 2019), ou seja, um aumento de 178,4%. Indivíduos residindo em áreas urbanas tiveram um aumento maior na prevalência de depressão ao longo do período de seis anos (39,8%), em comparação com os residentes em áreas rurais (20,2%). Houve um aumento na prevalência de depressão entre 2013 e 2019 para as piores categorias dos três comportamentos de saúde incluídos no estado, tanto em homens quanto em mulheres: etilismo, tabagismo e sedentarismo. Nossos resultados mostram um aumento significativo na prevalência de depressão nos seis anos entre as duas edições da PNS, principalmente entre homens mais jovens e desempregados. A recessão econômica no Brasil durante o período pode explicar esses achados.

El objetivo de este estudio es evaluar la variación nacional en la prevalencia general de depresión, así como en diferentes grupos sociodemográficos, comportamientos de salud, y macrorregiones del país entre 2013-2019. Los datos se obtuvieron de dos encuestas nacionales brasileñas -Encuesta Nacional de Salud 2013 y 2019-. Los participantes con edades entre los 18 años y con más edad incluyeron a 60 202 personas en 2013 y 88 531 en 2019. La depresión se evaluó mediante el Cuestionario de Salud del Paciente-9 (PHQ-9). Todas las estimaciones justificaron los pesos de la población y el muestreo complejo. Los resultados mostraron que durante seis años entre las dos encuestas, la prevalencia de depresión en Brasil se incrementó en un 36,7%, yendo de un 7,9% en 2013 a un 10,8% en el 2019, y este incremento es mayor entre adultos jóvenes, de 18 a 24 años de edad, que no estaban trabajando, donde casi había un incremento tres veces superior en la prevalencia de depresión (3,7 en 2013 y 10,3 en 2019), un incremento de un 178,4%. Aquellos que vivían en áreas urbanas tenían un incremento mayor en la prevalencia de depresión durante el período de seis años (39,8%), cuando se comparó con los residentes en áreas rurales (20,2%). Hubo un incremento en la prevalencia de depresión entre 2013-2019 para las peores categorías de los tres comportamientos de salud incluidos en el estudio para tanto hombres como mujeres: consumo excesivo de alcohol, fumar, y no practicar deporte al nivel recomendado de actividad física. Nuestros resultados muestran un significado incremento en la prevalencia de depresión durante los seis años entre las dos encuestas, principalmente entre los hombres más jóvenes y desempleados. La recesión económica del país durante este periodo puede explicar estos resultados.

The continuity of effect of schizophrenia polygenic risk score and patterns of cannabis use on transdiagnostic symptom dimensions at first-episode psychosis: findings from the EU-GEI study.

Diagnostic categories do not completely reflect the heterogeneous expression of psychosis. Using data from the EU-GEI study, we evaluated the impact of schizophrenia polygenic risk score (SZ-PRS) and patterns of cannabis use on the transdiagnostic expression of psychosis. We analysed first-episode psychosis patients (FEP) and controls, generating transdiagnostic dimensions of psychotic symptoms and experiences using item response bi-factor modelling. Linear regression was used to test the associations between these dimensions and SZ-PRS, as well as the combined effect of SZ-PRS and cannabis use on the dimensions of positive psychotic symptoms and experiences. We found associations between SZ-PRS and (1) both negative (B = 0.18; 95%CI 0.03-0.33) and positive (B = 0.19; 95%CI 0.03-0.35) symptom dimensions in 617 FEP patients, regardless of their categorical diagnosis; and (2) all the psychotic experience dimensions in 979 controls. We did not observe associations between SZ-PRS and the general and affective dimensions in FEP. Daily and current cannabis use were associated with the positive dimensions in FEP (B = 0.31; 95%CI 0.11-0.52) and in controls (B = 0.26; 95%CI 0.06-0.46), over and above SZ-PRS. We provide evidence that genetic liability to schizophrenia and cannabis use map onto transdiagnostic symptom dimensions, supporting the validity and utility of the dimensional representation of psychosis. In our sample, genetic liability to schizophrenia correlated with more severe psychosis presentation, and cannabis use conferred risk to positive symptomatology beyond the genetic risk. Our findings support the hypothesis that psychotic experiences in the general population have similar genetic substrates as clinical disorders.

The relationship of symptom dimensions with premorbid adjustment and cognitive characteristics at first episode psychosis: Findings from the EU-GEI study.

Premorbid functioning and cognitive measures may reflect gradients of developmental impairment across diagnostic categories in psychosis. In this study, we sought to examine the associations of current cognition and premorbid adjustment with symptom dimensions in a large first episode psychosis (FEP) sample. We used data from the international EU-GEI study. Bifactor modelling of the Operational Criteria in Studies of Psychotic Illness (OPCRIT) ratings provided general and specific symptom dimension scores. Premorbid Adjustment Scale estimated premorbid social (PSF) and academic adjustment (PAF), and WAIS-brief version measured IQ. A MANCOVA model examined the relationship between symptom dimensions and PSF, PAF, and IQ, having age, sex, country, self-ascribed ethnicity and frequency of cannabis use as confounders. In 785 patients, better PSF was associated with fewer negative (B = -0.12, 95% C.I. -0.18, -0.06, p < 0.001) and depressive (B = -0.09, 95% C.I. -0.15, -0.03, p = 0.032), and more manic (B = 0.07, 95% C.I. 0.01, 0.14, p = 0.023) symptoms. Patients with a lower IQ presented with slightly more negative and positive, and fewer manic, symptoms. Secondary analysis on IQ subdomains revealed associations between better perceptual reasoning and fewer negative (B = -0.09, 95% C.I. -0.17, -0.01, p = 0.023) and more manic (B = 0.10, 95% C.I. 0.02, 0.18, p = 0.014) symptoms. Fewer positive symptoms were associated with better processing speed (B = -0.12, 95% C.I. -0.02, -0.004, p = 0.003) and working memory (B = -0.10, 95% C.I. -0.18, -0.01, p = 0.024). These findings suggest that the negative and manic symptom dimensions may serve as clinical proxies of different neurodevelopmental predisposition in psychosis.

Risk Factors for Death Among 120,804 Hospitalized Patients with Confirmed COVID-19 in São Paulo, Brazil.

São Paulo is a state in Brazil with one of the highest numbers of confirmed and severe cases of coronavirus disease (COVID-19), with an incidence of 294 hospitalizations per 100,000 inhabitants. We report the clinical characteristics and outcomes of 120,804 hospitalized patients with confirmed COVID-19 from February 26 to October 10, 2020, in São Paulo. Characteristics of patients who died and survived were compared using a survival analysis. The median age was 60 years (interquartile range [IQR], 47-72), 67,821 (56.1%) were men, and 61,659 (51.0%) were white. Most hospitalized patients (79,812; 66.1%) reported one or more comorbidities, 41,708 (34.5%) hospitalized patients were admitted to intensive care units, and 33,079 (27.4%) died. Men (hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.18-1.25), elderly individuals (HR, 3.85; 95% CI, 3.68-4.02), and patients with chronic cardiovascular disease including hypertension (HR, 1.05; 95% CI, 1.02-1.08), chronic lung disease (HR, 1.38; 95% CI, 1.31-1.45), diabetes mellitus (HR, 1.14; 95% CI, 1.11-1.18), and chronic neurological disease (HR, 1.48; 95% CI, 1.41-1.55) were at higher risk for death from COVID-19.

The Independent Effects of Psychosocial Stressors on Subclinical Psychosis: Findings From the Multinational EU-GEI Study.

The influence of psychosocial stressors on psychosis risk has usually been studied in isolation and after the onset of the disorder, potentially ignoring important confounding relationships or the fact that some stressors that may be the consequence of the disorder rather than preexisting. The study of subclinical psychosis could help to address some of these issues. In this study, we investigated whether there was (i) an association between dimensions of subclinical psychosis and several psychosocial stressors including: childhood trauma, self-reported discrimination experiences, low social capital, and stressful life experiences, and (ii) any evidence of environment-environment (ExE) interactions between these factors. Data were drawn from the EUGEI study, in which healthy controls (N = 1497) and siblings of subjects with a psychotic disorder (N = 265) were included in six countries. The association between psychosocial stressors and subclinical psychosis dimensions (positive, negative and depressive dimension as measured by the Community Assessment of Psychic Experiences (CAPE) scale) and possible ExE interactions were assessed using linear regression models. After adjusting for sex, age, ethnicity, country, and control/sibling status, childhood trauma (ß for positive dimension: 0.13, negative: 0.49, depressive: 0.26) and stressful life events (positive: 0.08, negative: 0.16, depressive: 0.17) were associated with the three dimensions. Lower social capital was associated with the negative and depression dimensions (negative: 0.26, depressive: 0.13), and self-reported discrimination experiences with the positive dimension (0.06). Our findings are in favor of independent, cumulative and non-specific influences of social adversities in subclinical psychosis in non-clinical populations, without arguments for E × E interactions.

Burnout among primary health care workers in Brazil: results of a multilevel analysis.

PURPOSE: Burnout among health care workers may hamper the quality of care and effectiveness of health systems. Hence, we examined the prevalence of burnout in primary care teams, including community health workers; and investigated associations between individuals' characteristics, team and primary care center factors, and burnout. METHODS: We carried out a cross-sectional study among primary care teams in the city of São Paulo, Brazil (n = 2940). We randomly selected 66 primary care centers. The Maslach burnout inventory was used to investigate burnout. We used multilevel modelling to examine the associations between individuals' characteristics, team and primary care center variables with burnout. RESULTS: We addressed 351 primary care teams, with 11.4% of participants presenting severe burnout. The variance in burnout among primary care workers was partially explained by individuals' characteristics, and by team and primary care center factors. Severe burnout was associated with the following: (1) individuals' characteristics: being black, being younger, a higher length of employment in primary care, and presenting a lack of feedback from supervisors; (2) team factors: working in deprived areas and not receiving the support of a multidisciplinary team; and (3) primary care center factors: inadequate infrastructure (less than one office available per team), and having a bad/very bad relationship with the community council. CONCLUSIONS: To reduce burnout among primary care teams, stakeholders should: (1) train managers/supervisors on leadership styles that prioritize performance feedback, support, and communication skills; (2) allocate catchment areas to teams according to each community's vulnerability; (3) provide a multidisciplinary team to support primary care workers; and (4) offer suitable facilities and infra-structure.

Duration of Untreated Psychosis in First-Episode Psychosis is not Associated With Common Genetic Variants for Major Psychiatric Conditions: Results From the Multi-Center EU-GEI Study.

Duration of untreated psychosis (DUP) is associated with clinical outcomes in people with a diagnosis of first-episode psychosis (FEP), but factors associated with length of DUP are still poorly understood. Aiming to obtain insights into the possible biological impact on DUP, we report genetic analyses of a large multi-center phenotypically well-defined sample encompassing individuals with a diagnosis of FEP recruited from 6 countries spanning 17 research sites, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. Genetic propensity was measured using polygenic scores for schizophrenia (SZ-PGS), bipolar disorder (BD-PGS), major depressive disorder (MDD-PGS), and intelligence (IQ-PGS), which were calculated based on the results from the most recent genome-wide association meta-analyses. Following imputation for missing data and log transformation of DUP to handle skewedness, the association between DUP and polygenic scores (PGS), adjusting for important confounders, was investigated with multivariable linear regression models. The sample comprised 619 individuals with a diagnosis of FEP disorders with a median age at first contact of 29.0 years (interquartile range [IQR] = 22.0-38.0). The median length of DUP in the sample was 10.1 weeks (IQR = 3.8-30.8). One SD increases in SZ-PGS, BD-PGS, MDD-PGS or IQ-PGS were not significantly associated with the length of DUP. Our results suggest that genetic variation does not contribute to the DUP in patients with a diagnosis of FEP disorders.

Effect of a Digital Intervention on Depressive Symptoms in Patients With Comorbid Hypertension or Diabetes in Brazil and Peru: Two Randomized Clinical Trials.

Importance: Depression is a leading contributor to disease burden globally. Digital mental health interventions can address the treatment gap in low- and middle-income countries, but the effectiveness in these countries is unknown. Objective: To investigate the effectiveness of a digital intervention in reducing depressive symptoms among people with diabetes and/or hypertension. Design, Setting, and Participants: Participants with clinically significant depressive symptoms (Patient Health Questionnaire-9 [PHQ-9] score ≥10) who were being treated for hypertension and/or diabetes were enrolled in a cluster randomized clinical trial (RCT) at 20 sites in São Paulo, Brazil (N=880; from September 2016 to September 2017; final follow-up, April 2018), and in an individual-level RCT at 7 sites in Lima, Peru (N=432; from January 2017 to September 2017; final follow-up, March 2018). Interventions: An 18-session, low-intensity, digital intervention was delivered over 6 weeks via a provided smartphone, based on behavioral activation principles, and supported by nurse assistants (n = 440 participants in 10 clusters in São Paulo; n = 217 participants in Lima) vs enhanced usual care (n = 440 participants in 10 clusters in São Paulo; n = 215 participants in Lima). Main Outcomes and Measures: The primary outcome was a reduction of at least 50% from baseline in PHQ-9 scores (range, 0-27; higher score indicates more severe depression) at 3 months. Secondary outcomes included a reduction of at least 50% from baseline PHQ-9 scores at 6 months. Results: Among 880 patients cluster randomized in Brazil (mean age, 56.0 years; 761 [86.5%] women) and 432 patients individually randomized in Peru (mean age, 59.7 years; 352 [81.5%] women), 807 (91.7%) in Brazil and 426 (98.6%) in Peru completed at least 1 follow-up assessment. The proportion of participants in São Paulo with a reduction in PHQ-9 score of at least 50% at 3-month follow-up was 40.7% (159/391 participants) in the digital intervention group vs 28.6% (114/399 participants) in the enhanced usual care group (difference, 12.1 percentage points [95% CI, 5.5 to 18.7]; adjusted odds ratio [OR], 1.6 [95% CI, 1.2 to 2.2]; P = .001). In Lima, the proportion of participants with a reduction in PHQ-9 score of at least 50% at 3-month follow-up was 52.7% (108/205 participants) in the digital intervention group vs 34.1% (70/205 participants) in the enhanced usual care group (difference, 18.6 percentage points [95% CI, 9.1 to 28.0]; adjusted OR, 2.1 [95% CI, 1.4 to 3.2]; P < .001). At 6-month follow-up, differences across groups were no longer statistically significant. Conclusions and Relevance: In 2 RCTs of patients with hypertension or diabetes and depressive symptoms in Brazil and Peru, a digital intervention delivered over a 6-week period significantly improved depressive symptoms at 3 months when compared with enhanced usual care. However, the magnitude of the effect was small in the trial from Brazil and the effects were not sustained at 6 months. Trial Registration: ClinicalTrials.gov: NCT02846662 (São Paulo) and NCT03026426 (Lima).

Trend in the prevalence of depression and correlates in Brazil: results from the National Health Surveys 2013 and 2019

This study aims to evaluate national variation in depression prevalence overall and in different socioeconomic and demographic groups, health behaviors, and macro-regions of the country, between 2013 and 2019. Data were obtained from the National Health Surveys ­ PNS 2013 and 2019, which are cross-sectional surveys of the Brazilian general population. Participants aged 18 years and older included 60,202 individuals in 2013 and 88,531 in 2019. Depression was evaluated through the Patient Health Questionnaire-9 (PHQ-9). Calculations were carried out population-weighted. Additional age-standardized analyses were conducted to account for demographic changes. The results showed that in the six-year period between the two surveys, the prevalence of depression in Brazil increased by 36.7%, going from 7.9% in 2013 to 10.8% in 2019, this increase is more marked among young adults, 18 to 24 years old, who were not working, where there was a significant and almost three-fold absolute difference increase in the prevalence of depression (3.7 in 2013 and 10.3 in 2019), an increase of 178.4%. Those living in urban areas of the country had a greater increase in the prevalence of depression in the six-year period (39.8%) when compared to residents in rural areas (20.2%). There was an increase in the prevalence of depression between 2013 and 2019 for the worst categories of the three health behaviors under study, for both sexes: heavy drinking, smoking, and lack of physical activity, following the pattern observed for the general population. Our results show evidence of a significant increase in the prevalence of depression over the six-year period between the two surveys, mainly among the younger and unemployed men. The country´s economic context of recession during this period may be an explanation for this finding.