Transdiagnostic dimensions of symptoms and experiences associated with immune proteins in the continuity of psychosis.

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.

Exploring the mediation of DNA methylation across the epigenome between childhood adversity and First Episode of Psychosis-findings from the EU-GEI study.

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.

Synergistic effects of childhood adversity and polygenic risk in first-episode psychosis: the EU-GEI study.

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.

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.

The relationship between genetic liability, childhood maltreatment, and IQ: findings from the EU-GEI multicentric case-control study.

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.

The independent and combined effects of cannabis use and systemic inflammation during the early stages of psychosis: exploring the two-hit hypothesis.

BACKGROUND: Cannabis consumption is a modifiable risk factor associated with psychosis, but not all cannabis users develop psychosis. Animal studies suggest that an antecedent active immune system interacts with subsequent cannabis exposure and moderates the cannabis-psychosis association, supporting the two-hit hypothesis. The clinical investigations are few, and it is unclear if the immune system is a biological candidate moderating the cannabis-psychosis association or whether cannabis increases inflammation, which in turn, augments psychosis likelihood. METHODS: We explored the mediating and moderating role of blood inflammation using PROCESS macro. We used data from a cross-sectional study, including 153 first-episode psychosis patients and 256 community-based controls. Participants answered the Cannabis Experience Questionnaire (cannabis frequency, age of onset, and duration), and plasma cytokines were measured [interleukin (IL)-1ß, IL-6, IL-4, IL-10, tumour necrosis factor-α (TNF-α), interferon-γ (IFN-γ), transforming growth factor-ß (TGF-ß); multiplex]. We computed an inflammatory composite score (ICS) to represent the systemic inflammatory state. Confounders included sex, age, ethnicity, educational level, body mass index, tobacco smoking, lifetime use of other drugs, and antipsychotic treatment. RESULTS: Mediation: Cannabis consumption was not associated with increased inflammation, thus not supporting a mediating effect of inflammation. Moderation: Daily use and age of onset <17 interacted significantly with the ICS to increase the odds of psychosis beyond their individual effects and were only associated with psychosis among those scoring medium-high in the ICS. CONCLUSIONS: Immune dysregulation might be part of the pathophysiology of psychosis, not explained by cannabis use or other confounders. We provide the first and initial evidence that immune dysregulation modifies the cannabis-psychosis association, in line with a two-hit hypothesis.

Social disadvantage, linguistic distance, ethnic minority status and first-episode psychosis: results from the EU-GEI case-control study.

BACKGROUND: Ethnic minority groups in Western countries face an increased risk of psychotic disorders. Causes of this long-standing public health inequality remain poorly understood. We investigated whether social disadvantage, linguistic distance and discrimination contributed to these patterns. METHODS: We used case-control data from the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study, carried out in 16 centres in six countries. We recruited 1130 cases and 1497 population-based controls. Our main outcome measure was first-episode ICD-10 psychotic disorder (F20-F33), and exposures were ethnicity (white majority, black, mixed, Asian, North-African, white minority and other), generational status, social disadvantage, linguistic distance and discrimination. Age, sex, paternal age, cannabis use, childhood trauma and parental history of psychosis were included as a priori confounders. Exposures and confounders were added sequentially to multivariable logistic models, following multiple imputation for missing data. RESULTS: Participants from any ethnic minority background had crude excess odds of psychosis [odds ratio (OR) 2.03, 95% confidence interval (CI) 1.69-2.43], which remained after adjustment for confounders (OR 1.61, 95% CI 1.31-1.98). This was progressively attenuated following further adjustment for social disadvantage (OR 1.52, 95% CI 1.22-1.89) and linguistic distance (OR 1.22, 95% CI 0.95-1.57), a pattern mirrored in several specific ethnic groups. Linguistic distance and social disadvantage had stronger effects for first- and later-generation groups, respectively. CONCLUSION: Social disadvantage and linguistic distance, two potential markers of sociocultural exclusion, were associated with increased odds of psychotic disorder, and adjusting for these led to equivocal risk between several ethnic minority groups and the white majority.

Jumping to conclusions, general intelligence, and psychosis liability: findings from the multi-centre EU-GEI case-control study.

BACKGROUND: The 'jumping to conclusions' (JTC) bias is associated with both psychosis and general cognition but their relationship is unclear. In this study, we set out to clarify the relationship between the JTC bias, IQ, psychosis and polygenic liability to schizophrenia and IQ. METHODS: A total of 817 first episode psychosis patients and 1294 population-based controls completed assessments of general intelligence (IQ), and JTC, and provided blood or saliva samples from which we extracted DNA and computed polygenic risk scores for IQ and schizophrenia. RESULTS: The estimated proportion of the total effect of case/control differences on JTC mediated by IQ was 79%. Schizophrenia polygenic risk score was non-significantly associated with a higher number of beads drawn (B = 0.47, 95% CI -0.21 to 1.16, p = 0.17); whereas IQ PRS (B = 0.51, 95% CI 0.25-0.76, p < 0.001) significantly predicted the number of beads drawn, and was thus associated with reduced JTC bias. The JTC was more strongly associated with the higher level of psychotic-like experiences (PLEs) in controls, including after controlling for IQ (B = -1.7, 95% CI -2.8 to -0.5, p = 0.006), but did not relate to delusions in patients. CONCLUSIONS: Our findings suggest that the JTC reasoning bias in psychosis might not be a specific cognitive deficit but rather a manifestation or consequence, of general cognitive impairment. Whereas, in the general population, the JTC bias is related to PLEs, independent of IQ. The work has the potential to inform interventions targeting cognitive biases in early psychosis.

Daily use of high-potency cannabis is associated with more positive symptoms in first-episode psychosis patients: the EU-GEI case-control study.

BACKGROUND: Daily use of high-potency cannabis has been reported to carry a high risk for developing a psychotic disorder. However, the evidence is mixed on whether any pattern of cannabis use is associated with a particular symptomatology in first-episode psychosis (FEP) patients. METHOD: We analysed data from 901 FEP patients and 1235 controls recruited across six countries, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. We used item response modelling to estimate two bifactor models, which included general and specific dimensions of psychotic symptoms in patients and psychotic experiences in controls. The associations between these dimensions and cannabis use were evaluated using linear mixed-effects models analyses. RESULTS: In patients, there was a linear relationship between the positive symptom dimension and the extent of lifetime exposure to cannabis, with daily users of high-potency cannabis having the highest score (B = 0.35; 95% CI 0.14-0.56). Moreover, negative symptoms were more common among patients who never used cannabis compared with those with any pattern of use (B = -0.22; 95% CI -0.37 to -0.07). In controls, psychotic experiences were associated with current use of cannabis but not with the extent of lifetime use. Neither patients nor controls presented differences in depressive dimension related to cannabis use. CONCLUSIONS: Our findings provide the first large-scale evidence that FEP patients with a history of daily use of high-potency cannabis present with more positive and less negative symptoms, compared with those who never used cannabis or used low-potency types.

Perceived major experiences of discrimination, ethnic group, and risk of psychosis in a six-country case-control study.

BACKGROUND: Perceived discrimination is associated with worse mental health. Few studies have assessed whether perceived discrimination (i) is associated with the risk of psychotic disorders and (ii) contributes to an increased risk among minority ethnic groups relative to the ethnic majority. METHODS: We used data from the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions Work Package 2, a population-based case-control study of incident psychotic disorders in 17 catchment sites across six countries. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) for the associations between perceived discrimination and psychosis using mixed-effects logistic regression models. We used stratified and mediation analyses to explore differences for minority ethnic groups. RESULTS: Reporting any perceived experience of major discrimination (e.g. unfair treatment by police, not getting hired) was higher in cases than controls (41.8% v. 34.2%). Pervasive experiences of discrimination (≥3 types) were also higher in cases than controls (11.3% v. 5.5%). In fully adjusted models, the odds of psychosis were 1.20 (95% CI 0.91-1.59) for any discrimination and 1.79 (95% CI 1.19-1.59) for pervasive discrimination compared with no discrimination. In stratified analyses, the magnitude of association for pervasive experiences of discrimination appeared stronger for minority ethnic groups (OR = 1.73, 95% CI 1.12-2.68) than the ethnic majority (OR = 1.42, 95% CI 0.65-3.10). In exploratory mediation analysis, pervasive discrimination minimally explained excess risk among minority ethnic groups (5.1%). CONCLUSIONS: Pervasive experiences of discrimination are associated with slightly increased odds of psychotic disorders and may minimally help explain excess risk for minority ethnic groups.

Recruitment, training and supervision of nurses and nurse assistants for a task-shifting depression intervention in two RCTs in Brazil and Peru.

BACKGROUND: Task-shifting and technology in psychological interventions are two solutions to increasing access to mental health intervention and overcoming the treatment gap in low and middle-income countries. The CONEMO intervention combines a smartphone app with support from non-specialized professionals, aiming to treat depression in patients with diabetes and/or hypertension. The aim of this paper is to describe the process of recruitment, training and supervision of the non-specialized professionals who participated in the CONEMO task-shifting intervention in Brazil and Peru. METHODS: We described and analyzed data related to the recruitment, training and supervision of 62 nurse assistants from the health system in Sao Paulo, Brazil, and three hired nurses in Lima, Peru. The data were collected from information provided by nurses and nurse assistants, supervisor records from supervision meetings and the CONEMO platform database. RESULTS: We found that task-shifting was feasible using existing resources in Sao Paulo and additional human resources in Lima. Training and supervision were found to be crucial and well received by the staff; however, time was a limitation when using existing human resources. Ensuring technological competence prior to the start of the intervention was essential. Group supervision meetings allowed non-specialized professionals to learn from each other's experiences. CONCLUSION: Carefully considering recruitment, training and supervision of non-specialized professionals is important for effective task-shifting when delivering an mHealth intervention for depression. Opportunities and challenges of working in different health systems are described, which should be considered in future implementation, either for research or real settings. Trial registration NCT028406662 (Sao Paulo), NCT03026426 (Peru).

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.

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).

Cytokine profile in first-episode psychosis, unaffected siblings and community-based controls: the effects of familial liability and childhood maltreatment.

BACKGROUND: Inflammation is a possible biological mechanism underlying the association between childhood maltreatment and psychosis. Previous investigations on this regard were mainly conducted on chronic schizophrenia and lacked control for confounders. We aim to investigate the role of familial liability, childhood maltreatment and recent stress in determining cytokine abnormalities at the onset of psychosis. METHODS: We recruited 114 first-episode psychosis (FEP) patients, 57 unaffected biological siblings of FEP patients, and 251 community-based controls. Plasma cytokines (IL-1ß, IL-6, TNF-α, IFN-γ, IL-4, IL-10 and TGF-ß) were measured and differences across the groups analysed after adjusting for potential confounders. RESULTS: FEP had a higher pro- and anti-inflammatory cytokine profile (IL-1ß, IL-6, TNF-α, IL-10 and TGF-ß), which was not observed in unaffected siblings. Siblings presented decreased IL-1ß when compared with patients and controls. Childhood maltreatment was associated with higher levels of TGF-ß in both patients and siblings when compared with controls. Physical childhood abuse was associated with increased levels of TGF-ß in FEP patients but with decreased levels in controls. Other childhood maltreatment subtypes or recent stressors did not affect cytokine levels in any of the groups. CONCLUSIONS: Normal or reduced cytokines in siblings represent possibly a protective factor and suggest that the identified inflammatory profile in FEP can be a real pathophysiological component of psychosis. Experience of childhood maltreatment may contribute as long-term immune priming for the TGF-ß pathway, and increased levels of this cytokine in both patients and siblings exposed to childhood maltreatment point to a possible biological candidate of familial risk for psychosis.

The EUropean Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI): Incidence and First-Episode Case-Control Programme.

PURPOSE: The EUropean Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study contains an unparalleled wealth of comprehensive data that allows for testing hypotheses about (1) variations in incidence within and between countries, including by urbanicity and minority ethnic groups; and (2) the role of multiple environmental and genetic risk factors, and their interactions, in the development of psychotic disorders. METHODS: Between 2010 and 2015, we identified 2774 incident cases of psychotic disorders during 12.9 million person-years at risk, across 17 sites in 6 countries (UK, The Netherlands, France, Spain, Italy, and Brazil). Of the 2774 incident cases, 1130 cases were assessed in detail and form the case sample for case-control analyses. Across all sites, 1497 controls were recruited and assessed. We collected data on an extensive range of exposures and outcomes, including demographic, clinical (e.g. premorbid adjustment), social (e.g. childhood and adult adversity, cannabis use, migration, discrimination), cognitive (e.g. IQ, facial affect processing, attributional biases), and biological (DNA via blood sample/cheek swab). We describe the methodology of the study and some descriptive results, including representativeness of the cohort. CONCLUSIONS: This resource constitutes the largest and most extensive incidence and case-control study of psychosis ever conducted.

Urbanicity and risk of first-episode psychosis: incidence study in Brazil.

We estimated the incidence of first-episode psychosis over a 3-year period in a Brazilian catchment area comprising the region's main city, Ribeirão Preto (1 425 306 persons-years at risk), and 25 other municipalities with a total of 1 646 556 persons-years at risk. The incidence rates were estimated and adjusted by gender and age, using the direct standardisation method to the world population as reference. The incidence of psychosis was higher in the younger groups, men, and among Black and minority ethnic Brazilians. Psychosis incidence was lower in Ribeirão Preto (16.69/100 000 person-years at risk; 95% CI 15.68-17.70) compared with the average incidence in the remaining municipalities (21.25/100 000 person-years at risk; 95% CI 20.20-22.31), which have lower population density, suggesting a distinct role for urbanicity in the incidence of first-episode psychosis in low- and middle-income countries.

Transdiagnostic dimensions of psychopathology at first episode psychosis: findings from the multinational EU-GEI study.

BACKGROUND: The value of the nosological distinction between non-affective and affective psychosis has frequently been challenged. We aimed to investigate the transdiagnostic dimensional structure and associated characteristics of psychopathology at First Episode Psychosis (FEP). Regardless of diagnostic categories, we expected that positive symptoms occurred more frequently in ethnic minority groups and in more densely populated environments, and that negative symptoms were associated with indices of neurodevelopmental impairment. METHOD: This study included 2182 FEP individuals recruited across six countries, as part of the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study. Symptom ratings were analysed using multidimensional item response modelling in Mplus to estimate five theory-based models of psychosis. We used multiple regression models to examine demographic and context factors associated with symptom dimensions. RESULTS: A bifactor model, composed of one general factor and five specific dimensions of positive, negative, disorganization, manic and depressive symptoms, best-represented associations among ratings of psychotic symptoms. Positive symptoms were more common in ethnic minority groups. Urbanicity was associated with a higher score on the general factor. Men presented with more negative and less depressive symptoms than women. Early age-at-first-contact with psychiatric services was associated with higher scores on negative, disorganized, and manic symptom dimensions. CONCLUSIONS: Our results suggest that the bifactor model of psychopathology holds across diagnostic categories of non-affective and affective psychosis at FEP, and demographic and context determinants map onto general and specific symptom dimensions. These findings have implications for tailoring symptom-specific treatments and inform research into the mood-psychosis spectrum.

Depression and excess mortality in the elderly living in low- and middle-income countries: Systematic review and meta-analysis.

OBJECTIVE: To investigate the association between depression and mortality in the elderly living in low- and middle-income countries. METHODS: A systematic review and meta-analysis was performed. We searched in five electronic databases for observational studies investigating the association between mortality and depression. Two reviewers worked independently to select articles, extract data, and assess study quality. RESULTS: A total of 10 studies including 13 828 participants (2402 depressed and 11 426 nondepressed) from six countries (Brazil, four articles; China, two articles; Botswana, India, South Africa, and South Korea, one article) were included. The overall unadjusted relative risk (RR) of mortality in depressed relative to nondepressed participants was 1.62 (95% CI, 1.39-1.88; P < 0.001), with high heterogeneity (I2  = 66%; 95% CI, 33-83; P < 0.005). After adjustment for publication bias, the overall RR decreased to 1.60 (95% CI, 1.37-1.86; P < 0.001). No significant differences were observed between subgroups except those defined by study quality. The high-quality studies had a pooled RR of 1.48 (95% CI, 1.32-1.67; P < 0.001), while the low-quality studies resulted had a pooled RR of 1.82 (95% CI, 1.25-2.65; P < 0.005). CONCLUSIONS: Depression is associated with excess mortality in the elderly living in low- and middle-income countries. In addition, this excess mortality does not differ substantially from that found in high-income countries. This suggests environmental factors occurring in low- and middle-income countries might not have a direct association with the excess mortality in the depressed elderly.

Type of delivery is not associated with maternal depression.

Although many women experience depressive symptoms during the first year after childbirth, the relationship between type of delivery and maternal depression is not clear. The purpose of this study is to evaluate relationship between type of delivery and maternal depression, between 6 to 16 months after childbirth. We performed a prospective cohort study of 558 low-socioeconomic status pregnant women without depression. All participants were recruited from primary care clinics of the public sector in three administrative districts in the Western area of the city of São Paulo, Brazil. Depressive symptoms were assessed using the Self-Report Questionnaire (SRQ-20). Type of delivery was classified as uncomplicated spontaneous vaginal delivery (UVD) (no episiotomy and no more than a first-degree perineal laceration), complicated vaginal delivery (CVD) (episiotomy or more than a second-degree perineal laceration), and cesarean delivery (CD). Data about type of delivery were extracted from medical charts. Crude and adjusted risk ratios with 95% confidence intervals were estimated using Poisson regression with robust variance estimates to examine the association between type of delivery with maternal depression. Among 482 women reassessed during 6 to 16 months after delivery, 18% had symptoms of depression. According to the type of delivery, 250 (51.8%), 85 (21.7%), and 147 (30.5%) were UVD, CVD, and CD, respectively. There was no association between type of delivery and maternal depression. In comparison with women submitted to uncomplicated vaginal, women who had a cesarean or perineal trauma/episiotomy did not show greater risk of maternal depression, in the medium to long term after delivery.

Unplanned pregnancy and risk of maternal depression: secondary data analysis from a prospective pregnancy cohort.

PURPOSE: to evaluate the relationship between unplanned pregnancy (UP), a common problem in high and low income countries and maternal depression (MD). METHODS: Secondary analysis of data from a prospective cohort study with pregnant women recruited from 10 primary care clinics of the public sector in São Paulo, Brazil. Participants were questioned about pregnancy intention at 20-30 weeks of gestation. The Self Report Questionnaire score >7 was used to evaluated the presence of depression during pregnancy and 11 months after childbirth. Four groups of MD were defined: never; antenatal only; postnatal only; persistent (both antenatal/postnatal). Multinomial logistic regression was used to assess the relationship between UP and MD, controlling for confounding. RESULTS: Data were analysed for 701 at the postpartum period. Five hundred and sixty-two (67.8%) women did not plan the pregnancy. Women with UP had 2.5 more risk of being depressed during both assessments (during pregnancy and postpartum) when compared to women with a planned pregnancy (RR: 2.5; 95% CI: 1.47:4.30). In the adjusted models, women with UP were significantly more likely to have persistent depression (RR: 2.3; 95% CI: 1.2:4.3). CONCLUSION: UP is an independent risk factor for persistent depression, but not for postpartum depression.