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BACKGROUND: Suicide is a global health concern whose rates are soaring in many low-and-middle-income countries. Public awareness campaigns have been implemented in Brazil; however, their impact is uncertain. METHODS: This was an ecological study using population data from DATA-SUS, a Brazilian official notification system, selecting only deaths that were voluntarily self-inflicted (CID-10 × 60-X84). We analyzed all available data from 2000 to 2019 to assess trends before and after the national Yellow September (YS) campaign started in 2015. Differences in trends were assessed by Joinpoint Analysis (JA) and Regression Discontinuity Analysis (RDD), unadjusted and adjusted for economic factors. RESULTS: Overall, there was a progressive increase in the rate of relative (per 100,000 inhabitants) number of suicides over time between 2000 and 2019 (57 % increase). The JA detected a change in the slope of the curve representing an acceleration in suicides starting in the year 2015. Adjusted RDD revealed the year that Yellow September started significantly change the slope of the association between time and rates of suicide (pinteraction < 0.01), and marginal analysis detected the coefficient increased from 0.07 (95%CI 0.04-0.10) to 0.27 (95%CI -0.07-0.60) suicides/year per 100,000 inhabitants. LIMITATIONS: The ecological nature of the manuscript compromises causational implications. CONCLUSIONS: We found an increase in suicidal trends in Brazil, against the global trend that coincides with the beginning of a large national awareness campaign. Although we cannot attribute causality, our results reinforce the need of further studies to better understand the role of awareness campaigns in suicide reduction interventions, including potential unintended effects.
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Prevenção do Suicídio , Suicídio , Humanos , Brasil/epidemiologia , Suicídio/estatística & dados numéricos , Suicídio/tendências , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Promoção da Saúde , Adolescente , IdosoRESUMO
We characterized the neurocognitive profile of communed-based individuals and unaffected siblings of patients with psychosis from Brazil reporting psychotic experiences (PEs). We also analyzed associations between PEs and the intra and inter-functional connectivity (FC) in the Default Mode Network (DMN), the Fronto-Parietal Network (FPN) and the Salience Network (SN) measured by functional magnetic resonance imaging. The combined sample of communed-based individuals and unaffected siblings of patients with psychosis comprised 417 (neurocognition) and 85 (FC) volunteers who were divided as having low (<75th percentile) and high (≥75th percentile) PEs (positive, negative, and depressive dimensions) assessed by the Community Assessment of Psychic Experiences. The neurocognitive profile and the estimated current brief intellectual quotient (IQ) were assessed using the digit symbol (processing speed), arithmetic (working memory), block design (visual learning) and information (verbal learning) subtests of Wechsler Adult Intelligence Scale-third edition. Logistic regression models were performed for neurocognitive analysis. For neuroimaging, we used the CONN toolbox to assess FC between the specified regions, and ROI-to-ROI analysis. In the combined sample, high PEs (all dimensions) were related to lower processing speed performance. High negative PEs were related to poor visual learning performance and lower IQ, while high depressive PEs were associated with poor working memory performance. Those with high negative PEs presented FPN hypoconnectivity between the right and left lateral prefrontal cortex. There were no associations between PEs and the DMN and SN FC. Brazilian individuals with high PEs showed neurocognitive impairments like those living in wealthier countries. Hypoconnectivity in the FPN in a community sample with high PEs is coherent with the hypothesis of functional dysconnectivity in schizophrenia.
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Conectoma , Imageamento por Ressonância Magnética , Transtornos Psicóticos , Humanos , Masculino , Feminino , Adulto , Transtornos Psicóticos/fisiopatologia , Transtornos Psicóticos/diagnóstico por imagem , Adulto Jovem , Rede Nervosa/fisiopatologia , Rede Nervosa/diagnóstico por imagem , Rede de Modo Padrão/fisiopatologia , Rede de Modo Padrão/diagnóstico por imagem , Irmãos , Brasil , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Pessoa de Meia-Idade , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/diagnóstico por imagemRESUMO
OBJECTIVE: To ascertain whether sociodemographic and health-related characteristics known from previous research to have a substantive impact on recovery from depression modified the effect of a digital intervention designed to improve depressive symptoms (CONEMO). METHODS: The CONEMO study consisted of two randomized controlled trials, one conducted in Lima, Peru, and one in São Paulo, Brazil. As a secondary trial plan analysis, mixed logistic regression was used to explore interactions between the treatment arm and subgroups of interest defined by characteristics measured before randomization - suicidal ideation, race/color, age, gender, income, type of mobile phone, alcohol misuse, tobacco use, and diabetes/hypertension - in both trials. We estimated interaction effects between the treatment group and these subgroup factors for the secondary outcomes using linear mixed regression models. RESULTS: Increased effects of the CONEMO intervention on the primary outcome (reduction of at least 50% in depressive symptom scores at 3-month follow-up) were observed among older and wealthier participants in the Lima trial (p = 0.030 and p = 0.001, respectively). CONCLUSION: There was no evidence of such differential effects in São Paulo, and no evidence of impact of any other secondary outcomes in either trial. CLINICAL TRIAL REGISTRATION: NCT02846662 (São Paulo, Brazil - SP), NCT03026426 (Lima, Peru - LI).
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Depressão , Fatores Socioeconômicos , Telemedicina , Humanos , Masculino , Feminino , Brasil , Adulto , Pessoa de Meia-Idade , Peru , Depressão/terapia , Depressão/psicologia , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: There is limited evidence as to whether the immune protein profile is associated with a particular symptomatology pattern across the psychosis continuum. METHODS: We estimated two bifactor models of general and specific dimensions of psychotic experiences in unaffected siblings of patients (n = 52) and community controls (n = 200), and of psychotic symptoms in first-episode psychosis (FEP) patients (n = 110). We evaluated associations between these transdiagnostic dimensions and trait (TNF-α, IFN-γ), state (IL-6, IL-1ß), and regulatory (TGF-ß, IL-10, IL-4) cytokines. We explored whether schizophrenia genetic liability (schizophrenia polygenic risk score; SZ-PRS) modified the associations. RESULTS: High levels of trait marker IFN-γ were associated with the severity of general psychosis dimension in the unaffected siblings and community controls, expanding to the depressive dimension in siblings and to the manic dimension in FEP. High TNF-α levels were associated with more positive psychotic experiences in unaffected siblings and manic symptoms in FEP. Low levels of state markers IL-6 and IL-1ß were observed in unaffected siblings presenting more depressive experiences. Still, high levels of IL-6 and IL-1ß were associated with the severity of the depressive and negative symptom dimensions at FEP. The severity of transdiagnostic dimension scores across the three groups was associated with lower regulatory cytokines. Exploratory analysis suggested that a high SZ-PRS contributed mostly to associations with psychotic dimensions. CONCLUSIONS: IFN-γ mapped onto the multidimensional expression of psychosis, reinforcing the trait concept. State markers IL-6 and IL-1ß may fluctuate along the spectrum. Dysfunction in the regulatory arm may disinhibit the inflammatory system. Associations with psychotic dimensions may be more prone to SZ-PRS susceptibility.
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Objective: To ascertain whether sociodemographic and health-related characteristics known from previous research to have a substantive impact on recovery from depression modified the effect of a digital intervention designed to improve depressive symptoms (CONEMO). Methods: The CONEMO study consisted of two randomized controlled trials, one conducted in Lima, Peru, and one in São Paulo, Brazil. As a secondary trial plan analysis, mixed logistic regression was used to explore interactions between the treatment arm and subgroups of interest defined by characteristics measured before randomization - suicidal ideation, race/color, age, gender, income, type of mobile phone, alcohol misuse, tobacco use, and diabetes/hypertension - in both trials. We estimated interaction effects between the treatment group and these subgroup factors for the secondary outcomes using linear mixed regression models. Results: Increased effects of the CONEMO intervention on the primary outcome (reduction of at least 50% in depressive symptom scores at 3-month follow-up) were observed among older and wealthier participants in the Lima trial (p = 0.030 and p = 0.001, respectively). Conclusion: There was no evidence of such differential effects in São Paulo, and no evidence of impact of any other secondary outcomes in either trial. Clinical trial registration: NCT02846662 (São Paulo, Brazil - SP), NCT03026426 (Lima, Peru - LI). Funded by the U.S. National Institute of Mental Health (grant U19MH098780).
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Importance: Depression is a leading cause of disability worldwide, and there is increasing interest in nonpharmacological treatments. Auricular acupuncture (AA) is a simple, low-cost, and well-tolerated option, but further studies are needed to establish its efficacy and safety. Objective: To estimate the efficacy and safety of auricular acupuncture as a treatment for depression. Design, Setting, and Participants: This randomized clinical trial was conducted at 4 university research centers in Brazil, from March to July 2023. Eligible patients were adults aged 18 to 50 years whose score on the Patient Health Questionnaire-9 (PHQ-9) indicated moderate depression (score 10-14) or moderately severe depression (score 15-19). Exclusion criteria included previous application of AA, risk of suicidal ideation, or severe depression (PHQ-9 score >20). An intent-to-treat analysis and modified intent-to-treat analysis were conducted. Intervention: Participants were randomized into 2 treatment groups, which included specific AA (SA) and nonspecific AA (NSA). Both groups received 12 sessions of AA with semipermanent needles with daily stimulation twice a week over 6 weeks and were followed-up for 3 months. All participants continued with their usual care for ethical reasons. The SA group's treatment protocol consisted of 6 acupuncture points on the auricular pavilion chosen according to the diagnosis of depression by traditional Chinese medicine (Shenmen, subcortex, heart, lung, liver, and kidney). The NSA group's acupuncture points were the external ear, the cheek and face area, and 4 nonspecific points in the helix region unassociated with mental health symptoms. A locator device was used to confirm which areas had neuroreactive points. Main Outcomes and Measures: The primary outcome was a reduction of at least 50% in the PHQ-9 score (ie, depression recovery) at 3 months. Secondary outcomes included depression recovery at 4 and 6 weeks; depression remission (PHQ-9 score < 5) at 4 weeks, 6 weeks, and 3 months); and adverse events. Results: A total of 304 participants were screened, and 74 participants (62 women [84%]; median [IQR] age, 29 [23-27] years) were included in the intention-to-treat analysis, with 37 participants randomized to each group (SA and NSA). A total of 47 participants (64%) were followed-up through 3 months. The results showed no statistically significant difference in depressive recovery between the groups at 3 months (14 of 24 participants in the SA group [58%] vs 10 of 23 participants in the NSA group [43%]; risk ratio [RR], 1.34; 95% CI, 0.76-2.45; P = .38). The proportions of depression recovery and remission at 4 and 6 weeks based on the PHQ-9 were higher in the SA group (except for depression recovery at 6 weeks) with no statistically significant differences. However, a statistically significant difference was observed in symptom remission at 3 months (11 of 24 participants in the SA group [46%] vs 3 of 23 participants in the NSA group [13%]; RR, 1.99; 95% CI, 1.16-3.34; P = .02) in favor of SA. There were no significant differences in adverse event rates between the groups, evidencing the intervention's safety. Most participants reported mild pain at the needle application site (33 patients [94%] in the SA group vs 32 patients [91%] in the NSA group). Five participants dropped out of the study due to adverse events. Conclusions and Relevance: The results of this randomized clinical trial suggest that SA over 6 weeks is safe. Although there was no statistically significant difference between groups for the primary efficacy outcome, patients receiving SA did experience greater symptom remission at 3 months. A larger sample size and longer intervention are needed to further evaluate the efficacy of SA for depression. Trial Registration: ClinicalTrials.gov Identifier: NCT05855421.
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Terapia por Acupuntura , Acupuntura Auricular , Transtorno Depressivo , Adulto , Humanos , Feminino , Depressão/terapia , BrasilRESUMO
BACKGROUND: Use of illegal stimulants is associated with an increased risk of psychotic disorder. However, the impact of stimulant use on odds of first-episode psychosis (FEP) remains unclear. Here, we aimed to describe the patterns of stimulant use and examine their impact on odds of FEP. METHODS: We included patients with FEP aged 18-64 years who attended psychiatric services at 17 sites across 5 European countries and Brazil, and recruited controls representative of each local population (FEP = 1130; controls = 1497). Patterns of stimulant use were described. We computed fully adjusted logistic regression models (controlling for age, sex, ethnicity, cannabis use, and education level) to estimate their association with odds of FEP. Assuming causality, we calculated the population-attributable fractions for stimulant use associated with the odds for FEP. FINDINGS: Prevalence of lifetime and recent stimulant use in the FEP sample were 14.50% and 7.88% and in controls 10.80% and 3.8%, respectively. Recent and lifetime stimulant use was associated with increased odds of FEP compared with abstainers [fully adjusted odds ratio 1.74,95% confidence interval (CI) 1.20-2.54, P = .004 and 1.62, 95% CI 1.25-2.09, P < .001, respectively]. According to PAFs, a substantial number of FEP cases (3.35% [95% CI 1.31-4.78] for recent use and 7.61% [95% CI 3.68-10.54] for lifetime use) could have been prevented if stimulants were no longer available and the odds of FEP and PAFs for lifetime and recent stimulant use varied across countries. INTERPRETATION: Illegal stimulant use has a significant and clinically relevant influence on FEP incidence, with varying impacts across countries.
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Cannabis , Estimulantes do Sistema Nervoso Central , Transtornos Psicóticos , Humanos , Transtornos Psicóticos/epidemiologia , Transtornos Psicóticos/psicologia , Cannabis/efeitos adversos , Europa (Continente) , Etnicidade , IncidênciaRESUMO
This study investigated if the association between childhood maltreatment and cognition among psychosis patients and community controls was partially accounted for by genetic liability for psychosis. Patients with first-episode psychosis (N = 755) and unaffected controls (N = 1219) from the EU-GEI study were assessed for childhood maltreatment, intelligence quotient (IQ), family history of psychosis (FH), and polygenic risk score for schizophrenia (SZ-PRS). Controlling for FH and SZ-PRS did not attenuate the association between childhood maltreatment and IQ in cases or controls. Findings suggest that these expressions of genetic liability cannot account for the lower levels of cognition found among adults maltreated in childhood.
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Maus-Tratos Infantis , Transtornos Psicóticos , Esquizofrenia , Adulto , Humanos , Criança , Estudos de Casos e Controles , Transtornos Psicóticos/genética , Esquizofrenia/epidemiologia , Esquizofrenia/genética , CogniçãoRESUMO
BACKGROUND: A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to the number of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing polygenic vulnerability. Here, we investigated, in the largest sample of first-episode psychosis (FEP) cases to date, whether childhood adversity and high polygenic risk scores for schizophrenia (SZ-PRS) combine synergistically to increase the risk of psychosis, over and above the effect of each alone. METHODS: We assigned a schizophrenia-polygenic risk score (SZ-PRS), calculated from the Psychiatric Genomics Consortium (PGC2), to all participants in a sample of 384 FEP patients and 690 controls from the case-control component of the EU-GEI study. Only participants of European ancestry were included in the study. A history of childhood adversity was collected using the Childhood Trauma Questionnaire (CTQ). Synergistic effects were estimated using the interaction contrast ratio (ICR) [odds ratio (OR)exposure and PRS - ORexposure - ORPRS + 1] with adjustment for potential confounders. RESULTS: There was some evidence that the combined effect of childhood adversities and polygenic risk was greater than the sum of each alone, as indicated by an ICR greater than zero [i.e. ICR 1.28, 95% confidence interval (CI) -1.29 to 3.85]. Examining subtypes of childhood adversities, the strongest synergetic effect was observed for physical abuse (ICR 6.25, 95% CI -6.25 to 20.88). CONCLUSIONS: Our findings suggest possible synergistic effects of genetic liability and childhood adversity experiences in the onset of FEP, but larger samples are needed to increase precision of estimates.
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Experiências Adversas da Infância , Transtornos Psicóticos , Humanos , Transtornos Psicóticos/etiologia , Transtornos Psicóticos/genética , Genômica , Herança Multifatorial , Razão de ChancesRESUMO
ABTRACT: Studies conducted in psychotic disorders have shown that DNA-methylation (DNAm) is sensitive to the impact of Childhood Adversity (CA). However, whether it mediates the association between CA and psychosis is yet to be explored. Epigenome wide association studies (EWAS) using the Illumina Infinium-Methylation EPIC array in peripheral blood tissue from 366 First-episode of psychosis and 517 healthy controls was performed. Adversity scores were created for abuse, neglect and composite adversity with the Childhood Trauma Questionnaire (CTQ). Regressions examining (I) CTQ scores with psychosis; (II) with DNAm EWAS level and (III) between DNAm and caseness, adjusted for a variety of confounders were conducted. Divide-Aggregate Composite-null Test for the composite null-hypothesis of no mediation effect was conducted. Enrichment analyses were conducted with missMethyl package and the KEGG database. Our results show that CA was associated with psychosis (Composite: OR = 1.68; p = <0.001; abuse: OR = 2.16; p < 0.001; neglect: OR = 2.27; p = <0.001). None of the CpG sites significantly mediated the adversity-psychosis association after Bonferroni correction (p < 8.1 × 10-8). However, 28, 34 and 29 differentially methylated probes associated with 21, 27, 20 genes passed a less stringent discovery threshold (p < 5 × 10-5) for composite, abuse and neglect respectively, with a lack of overlap between abuse and neglect. These included genes previously associated to psychosis in EWAS studies, such as PANK1, SPEG TBKBP1, TSNARE1 or H2R. Downstream gene ontology analyses did not reveal any biological pathways that survived false discovery rate correction. Although at a non-significant level, DNAm changes in genes previously associated with schizophrenia in EWAS studies may mediate the CA-psychosis association. These results and associated involved processes such as mitochondrial or histaminergic disfunction, immunity or neural signalling requires replication in well powered samples. The lack of overlap between mediating genes associated with abuse and neglect suggests differential biological trajectories linking CA subtypes and psychosis.
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Experiências Adversas da Infância , Testes Psicológicos , Transtornos Psicóticos , Autorrelato , Humanos , Criança , Metilação de DNA/genética , Epigenoma , Transtornos Psicóticos/genéticaRESUMO
Objectives: 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 conducted 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 were included in the systematic review and 43 were included in the meta-analysis. The 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, with 26.8% being cohort studies. In the subanalyses, 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.
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OBJECTIVES: Gene-environment interactions increase the risk of psychosis. The objective of this study was 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 encoding D2R (DRD2: rs1799978, rs7131056, rs6275), NMDAR (GRIN1: rs4880213, rs11146020; GRIN2A: rs1420040, rs11866328; GRIN2B: rs890, rs2098469, rs7298664), and CB1R (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. Gene-gene and gene-environment associations were assessed using nonparametric Multifactor Dimensionality Reduction software. RESULTS: Single-locus analyses among the 23 SNVs for 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 an SNV in CNR1 and cannabis use. The best-performing model was the combination of 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 T-allele carriers of CNR1 SNVs, childhood trauma, and cannabis use.
Assuntos
Experiências Adversas da Infância , Cannabis , Transtornos Psicóticos , Humanos , Cannabis/efeitos adversos , Genótipo , Polimorfismo de Nucleotídeo Único/genética , Transtornos Psicóticos/genética , Receptor CB1 de Canabinoide/genéticaRESUMO
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.
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Hospitais Psiquiátricos , Transtornos Relacionados ao Uso de Substâncias , Recém-Nascido , Humanos , Masculino , Feminino , Brasil/epidemiologia , Seguimentos , Fatores de Risco , Causas de MorteRESUMO
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 conducted 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 were included in the systematic review and 43 were included in the meta-analysis. The 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, with 26.8% being cohort studies. In the subanalyses, 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.
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Agressão , Espiritualidade , Adolescente , Humanos , Agressão/psicologia , Pessoal de Saúde , ViolênciaRESUMO
Objectives: Gene-environment interactions increase the risk of psychosis. The objective of this study was 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 encoding D2R (DRD2: rs1799978, rs7131056, rs6275), NMDAR (GRIN1: rs4880213, rs11146020; GRIN2A: rs1420040, rs11866328; GRIN2B: rs890, rs2098469, rs7298664), and CB1R (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. Gene-gene and gene-environment associations were assessed using nonparametric Multifactor Dimensionality Reduction software. Results: Single-locus analyses among the 23 SNVs for 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 an SNV in CNR1 and cannabis use. The best-performing model was the combination of 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 T-allele carriers of CNR1 SNVs, childhood trauma, and cannabis use.
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Background and Hypothesis: It is argued that availability of diagnostic models will facilitate a more rapid identification of individuals who are at a higher risk of first episode psychosis (FEP). Therefore, we developed, evaluated, and validated a diagnostic risk estimation model to classify individual with FEP and controls across six countries. Study Design: We used data from a large multi-center study encompassing 2627 phenotypically well-defined participants (aged 18-64 years) recruited from six countries spanning 17 research sites, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions study. To build the diagnostic model and identify which of important factors for estimating an individual risk of FEP, we applied a binary logistic model with regularization by the least absolute shrinkage and selection operator. The model was validated employing the internal-external cross-validation approach. The model performance was assessed with the area under the receiver operating characteristic curve (AUROC), calibration, sensitivity, and specificity. Study Results: Having included preselected 22 predictor variables, the model was able to discriminate adults with FEP and controls with high accuracy across all six countries (rangesAUROCâ =â 0.84-0.86). Specificity (rangeâ =â 73.9-78.0%) and sensitivity (rangeâ =â 75.6-79.3%) were equally good, cumulatively indicating an excellent model accuracy; though, calibration slope for the diagnostic model showed a presence of some overfitting when applied specifically to participants from France, the UK, and The Netherlands. Conclusions: The new FEP model achieved a good discrimination and good calibration across six countries with different ethnic contributions supporting its robustness and good generalizability.
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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.
Assuntos
Armadilhas Extracelulares , Esquizofrenia , Estresse Psicológico , Animais , Ratos , Interleucina-6 , NeutrófilosRESUMO
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.
RESUMO
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.
RESUMO
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.