Neurocognition and brain functional connectivity in a non-clinical population-based sample with psychotic experiences.

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.

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.

Low doses of fluoxetine for the treatment of emotional premenstrual syndrome: a randomized double-blind, placebo-controlled, pilot study.

INTRODUCTION: The neuroactive metabolite of progesterone, allopregnanolone (ALLO), has been implicated in premenstrual syndrome (PMS) physiopathology and preclinical studies suggested that low doses of fluoxetine increase the ALLO brain concentration. OBJECTIVES: To assess which low dose of fluoxetine (2 mg/d, 5 mg/d or 10 mg/d), administered exclusively during the luteal phase of menstrual cycle, has a potential effect for preventing or mitigating emotional PMS symptoms. METHODS: In this randomized, double-blind, placebo-controlled pilot study, we followed 40 women (mean age = 29.7 +/- 7.4 years) with emotional PMS, during two menstrual cycles: cycle 1, without pharmacological intervention; and cycle 2, with pharmacological intervention. Participants took capsules, on average, seven days preceding the likely date of menses. We assessed the severity of PMS symptoms in both cycles using the Daily Record of Severity of Problems scale (DRSP). RESULTS: There was an increase in the DRSP scores during the late luteal phase of cycle 1, confirming the diagnosis of emotional PMS. Low doses of fluoxetine (5 mg/d: 33.5%; 10 mg/d: 48.4%) reduced DRSP total score in the day before menses (day-1) at cycle 2 compared with day-1 at cycle 1. Fluoxetine 10 mg/d had the most consistent decline in emotional PMS symptoms; 70% of the participants reported a reduction greater than 40% in the DRSP score. CONCLUSIONS: Low doses of fluoxetine, which may have no or few effect on the serotonergic system, but may interfere in the progesterone metabolization, seem to have some potential to mitigate emotional PMS symptoms. While the 10 mg/d of fluoxetine had the best performance on reducing emotional PMS symptoms, the 5 mg/d dose also seems to have some effect on emotional PMS symptoms. Further larger studies will help establish the lowest effective dose of flouxetine for PMS treatment.

Differences in Patterns of Stimulant Use and Their Impact on First-Episode Psychosis Incidence: An Analysis of the EUGEI Study.

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.

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.

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.

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.

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

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.

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.

Child maltreatment, migration and risk of first-episode psychosis: results from the multinational EU-GEI study.

BACKGROUND: Child maltreatment (CM) and migrant status are independently associated with psychosis. We examined prevalence of CM by migrant status and tested whether migrant status moderated the association between CM and first-episode psychosis (FEP). We further explored whether differences in CM exposure contributed to variations in the incidence rates of FEP by migrant status. METHODS: We included FEP patients aged 18-64 years in 14 European sites and recruited controls representative of the local populations. Migrant status was operationalized according to generation (first/further) and region of origin (Western/non-Western countries). The reference population was composed by individuals of host country's ethnicity. CM was assessed with Childhood Trauma Questionnaire. Prevalence ratios of CM were estimated using Poisson regression. We examined the moderation effect of migrant status on the odds of FEP by CM fitting adjusted logistic regressions with interaction terms. Finally, we calculated the population attributable fractions (PAFs) for CM by migrant status. RESULTS: We examined 849 FEP cases and 1142 controls. CM prevalence was higher among migrants, their descendants and migrants of non-Western heritage. Migrant status, classified by generation (likelihood test ratio:χ2 = 11.3, p = 0.004) or by region of origin (likelihood test ratio:χ2 = 11.4, p = 0.003), attenuated the association between CM and FEP. PAFs for CM were higher among all migrant groups compared with the reference populations. CONCLUSIONS: The higher exposure to CM, despite a smaller effect on the odds of FEP, accounted for a greater proportion of incident FEP cases among migrants. Policies aimed at reducing CM should consider the increased vulnerability of specific subpopulations.

First-Episode Psychosis Patients Who Deteriorated in the Premorbid Period Do Not Have Higher Polygenic Risk Scores Than Others: A Cluster Analysis of EU-GEI Data.

Cluster studies identified a subgroup of patients with psychosis whose premorbid adjustment deteriorates before the onset, which may reflect variation in genetic influence. However, other studies reported a complex relationship between distinctive patterns of cannabis use and cognitive and premorbid impairment that is worthy of consideration. We examined whether: (1) premorbid social functioning (PSF) and premorbid academic functioning (PAF) in childhood and adolescence and current intellectual quotient (IQ) define different clusters in 802 first-episode of psychosis (FEP) patients; resulting clusters vary in (2) polygenic risk scores (PRSs) for schizophrenia (SCZ_PRS), bipolar disorder (BD_PRS), major depression (MD_PRS), and IQ (IQ_PRS), and (3) patterns of cannabis use, compared to 1,263 population-based controls. Four transdiagnostic clusters emerged (BIC = 2268.5): (1) high-cognitive-functioning (n = 205), with the highest IQ (Mean = 106.1, 95% CI: 104.3, 107.9) and PAF, but low PSF. (2) Low-cognitive-functioning (n = 223), with the lowest IQ (Mean = 73.9, 95% CI: 72.2, 75.7) and PAF, but normal PSF. (3) Intermediate (n = 224) (Mean_IQ = 80.8, 95% CI: 79.1, 82.5) with low-improving PAF and PSF. 4) Deteriorating (n = 150) (Mean_IQ = 80.6, 95% CI: 78.5, 82.7), with normal-deteriorating PAF and PSF. The PRSs explained 7.9% of between-group membership. FEP had higher SCZ_PRS than controls [F(4,1319) = 20.4, P < .001]. Among the clusters, the deteriorating group had lower SCZ_PRS and was likelier to have used high-potency cannabis daily. Patients with FEP clustered according to their premorbid and cognitive abilities. Pronounced premorbid deterioration was not typical of most FEP, including those more strongly predisposed to schizophrenia, but appeared in a cluster with a history of high-potency cannabis use.

Lifetime cannabis use and childhood trauma increase risk of psychosis in carriers of CNR1 genetic variants: findings from the STREAM study

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.

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.

Validation of the Brazilian version of the Hinting Task and Facial Emotion Recognition Test (FERT-100) in patients with schizophrenia / Validação da versão brasileira do Hinting Task e do Teste de Reconhecimento de Emoções Faciais (FERT-100) em pacientes com esquizofrenia

ABSTRACT Social cognition is an especially relevant domain in schizophrenia due to its association with functional impairment. However, we still do not have studies that have validated instruments with internationally established psychometric qualities for the Brazilian population. Objectives: This study aimed to present psychometric qualities and contribute to the validation of the Brazilian version of the Hinting Task and Facial Emotion Recognition Test (FERT-100). Methods: A total of 104 stabilized patients living in the community diagnosed with schizophrenia and 89 controls were evaluated. We assess the psychometric properties of Hinting Task and FERT-100 for discriminant construct validity, divergent construct validity, convergent construct validity, concurrent criterion validity, and reliability. Results: There is a statistically significant difference between patients and controls regarding social cognition (Hinting Task: Z=6.85, p<0.001; FERT-100: t=4.88, p<0.001). The main predictors of variation in social cognition were the neurocognitive domains. The associations between social cognition tests and other studied variables are similar to what is found in the literature. Social cognition maintains correlation with functional capacity even when neurocognition is taken into account. Conclusions: The validity of the Brazilian version of Hinting Task and FERT-100 can be determined, since the relationship of these tests with other clinical variables is similar to that observed in the literature.

RESUMO A cognição social é um domínio especialmente relevante na esquizofrenia devido à sua associação com o comprometimento funcional. No entanto, ainda não temos estudos que validaram instrumentos com qualidades psicométricas internacionalmente estabelecidas para a população brasileira. Objetivos: Apresentar as qualidades psicométricas e contribuir para a validação da versão brasileira do Hinting Task e do Teste de Reconhecimento de Emoções Faciais (FERT-100). Métodos: Foram avaliados 104 pacientes estabilizados residentes na comunidade com diagnóstico de esquizofrenia e 89 controles. Avaliou-se as propriedades psicométricas do Hinting Task e FERT-100 para validade de construto discriminante, validade de construto divergente, validade de construto convergente, validade de critério concorrente e confiabilidade. Resultados: Houve uma diferença estatisticamente significativa entre pacientes e controles quanto à cognição social (Hinting Task: Z=6,85; p<0,001. FERT-100: t=4,88; p<0,001). Os principais preditores da variação na cognição social foram os domínios neurocognitivos. As associações entre os testes de cognição social e outras variáveis estudadas são semelhantes às encontradas na literatura. A cognição social mantém correlação com a capacidade funcional mesmo quando a neurocognição é levada em consideração. Conclusões: A validade da versão brasileira do Hinting Task e do FERT-100 pode ser determinada, pois a relação desses testes com outras variáveis clínicas é semelhante à observada na literatura.

Preterm birth and postpartum depression within 6 months after childbirth in a Brazilian cohort.

Preterm birth (PTB) and postpartum depression (PPD) are important public health issues, and although literature mainly supports the association between them, some reviews have highlighted methodological limitations in the studies in this field, restricting the interpretation of such finding. This study aimed at assessing the association between PTB and PPD, by comparing groups of preterm and full-term mothers in two Brazilian cities with contrasting sociodemographic indicators. This prospective convenience cohort study assessed 1421 women during pregnancy, at childbirth, and in the postpartum period. The Edinburgh Postnatal Depression Scale (EPDS) was administrated to assess PPD within 6 months after delivery and women were considered probably depressed if scores were EDPS ≥ 12. PTB was defined as the delivery before 37 completed weeks of pregnancy. A multivariate Poisson regression was used to estimate relative risk for PPD in mothers of preterm infants, and the final analysis models were adjusted for psychosocial variables, selected according to the directed acyclic graph (DAG) approach. Frequencies of PPD were not significantly different in mothers of preterm and full-term infants, in neither city. In the final adjusted model, PTB was not associated with PPD. The association between PTB and PPD was not confirmed in two large samples from two Brazilian cities with contrasting socioeconomic profile. However, maternal health during pregnancy plays an important role in predicting PPD. Prenatal care should promote maternal mental health as an effort towards decreasing unfavored outcomes for mothers, infants, and families.

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.

Validation of the Brazilian version of the Hinting Task and Facial Emotion Recognition Test (FERT-100) in patients with schizophrenia.

Social cognition is an especially relevant domain in schizophrenia due to its association with functional impairment. However, we still do not have studies that have validated instruments with internationally established psychometric qualities for the Brazilian population. Objectives: This study aimed to present psychometric qualities and contribute to the validation of the Brazilian version of the Hinting Task and Facial Emotion Recognition Test (FERT-100). Methods: A total of 104 stabilized patients living in the community diagnosed with schizophrenia and 89 controls were evaluated. We assess the psychometric properties of Hinting Task and FERT-100 for discriminant construct validity, divergent construct validity, convergent construct validity, concurrent criterion validity, and reliability. Results: There is a statistically significant difference between patients and controls regarding social cognition (Hinting Task: Z=6.85, p<0.001; FERT-100: t=4.88, p<0.001). The main predictors of variation in social cognition were the neurocognitive domains. The associations between social cognition tests and other studied variables are similar to what is found in the literature. Social cognition maintains correlation with functional capacity even when neurocognition is taken into account. Conclusions: The validity of the Brazilian version of Hinting Task and FERT-100 can be determined, since the relationship of these tests with other clinical variables is similar to that observed in the literature.

A cognição social é um domínio especialmente relevante na esquizofrenia devido à sua associação com o comprometimento funcional. No entanto, ainda não temos estudos que validaram instrumentos com qualidades psicométricas internacionalmente estabelecidas para a população brasileira. Objetivos: Apresentar as qualidades psicométricas e contribuir para a validação da versão brasileira do Hinting Task e do Teste de Reconhecimento de Emoções Faciais (FERT-100). Métodos: Foram avaliados 104 pacientes estabilizados residentes na comunidade com diagnóstico de esquizofrenia e 89 controles. Avaliou-se as propriedades psicométricas do Hinting Task e FERT-100 para validade de construto discriminante, validade de construto divergente, validade de construto convergente, validade de critério concorrente e confiabilidade. Resultados: Houve uma diferença estatisticamente significativa entre pacientes e controles quanto à cognição social (Hinting Task: Z=6,85; p<0,001. FERT-100: t=4,88; p<0,001). Os principais preditores da variação na cognição social foram os domínios neurocognitivos. As associações entre os testes de cognição social e outras variáveis estudadas são semelhantes às encontradas na literatura. A cognição social mantém correlação com a capacidade funcional mesmo quando a neurocognição é levada em consideração. Conclusões: A validade da versão brasileira do Hinting Task e do FERT-100 pode ser determinada, pois a relação desses testes com outras variáveis clínicas é semelhante à observada na literatura.

Early intervention in psychosis in emerging countries: Findings from a first-episode psychosis programme in the Ribeirão Preto catchment area, southeastern Brazil.

AIM: People presenting with first-episode psychosis (FEP) can benefit from early intervention programmes. However, such programmes are scarce in low- and middle-income countries (LMICs). In Brazil, there are a few programmes, but they are unequally distributed across the country. We aimed to describe the implementation and performance of the Ribeirão Preto Early Intervention in Psychosis Programme (Ribeirão Preto-EIP), an outpatient service for patients presenting with FEP residing in the Ribeirão Preto catchment area in Southeastern Brazil. METHODS: A detailed description of the service, staff and theoretical framework was compiled. Furthermore, a retrospective cohort study of patients attending the programme throughout 4 years (2015-2018) was conducted. Data were obtained by analysing the medical records of all patients, and sociodemographic and diagnostic stability information for this period was recorded. RESULTS: The Ribeirão Preto-EIP had 358 new referrals during the study period. Among them, 237 patients were assessed for an average (median) duration of 14 months. Most patients were male (64.1%) and single (84.8%). The median age was 23.5 years (range, 9-86 years). Schizophrenia was the main diagnosis (43.4%), followed by substance-induced (25.7%) and affective (18.6%) psychosis. Referrals occurred from emergency, inpatient, community-based mental health and primary care services. CONCLUSIONS: Programmes such as the Ribeirão Preto-EIP demonstrate that early intervention in psychosis is feasible in LMICs despite significant challenges for their access and integration in the health system. Strategic scale-up policies could be undertaken to offer better short- and long-term outcomes for individuals presenting with FEP and their families.

Migration history and risk of psychosis: results from the multinational EU-GEI study.

BACKGROUND: Psychosis rates are higher among some migrant groups. We hypothesized that psychosis in migrants is associated with cumulative social disadvantage during different phases of migration. METHODS: We used data from the EUropean Network of National Schizophrenia Networks studying Gene-Environment Interactions (EU-GEI) case-control study. We defined a set of three indicators of social disadvantage for each phase: pre-migration, migration and post-migration. We examined whether social disadvantage in the pre- and post-migration phases, migration adversities, and mismatch between achievements and expectations differed between first-generation migrants with first-episode psychosis and healthy first-generation migrants, and tested whether this accounted for differences in odds of psychosis in multivariable logistic regression models. RESULTS: In total, 249 cases and 219 controls were assessed. Pre-migration (OR 1.61, 95% CI 1.06-2.44, p = 0.027) and post-migration social disadvantages (OR 1.89, 95% CI 1.02-3.51, p = 0.044), along with expectations/achievements mismatch (OR 1.14, 95% CI 1.03-1.26, p = 0.014) were all significantly associated with psychosis. Migration adversities (OR 1.18, 95% CI 0.672-2.06, p = 0.568) were not significantly related to the outcome. Finally, we found a dose-response effect between the number of adversities across all phases and odds of psychosis (⩾6: OR 14.09, 95% CI 2.06-96.47, p = 0.007). CONCLUSIONS: The cumulative effect of social disadvantages before, during and after migration was associated with increased odds of psychosis in migrants, independently of ethnicity or length of stay in the country of arrival. Public health initiatives that address the social disadvantages that many migrants face during the whole migration process and post-migration psychological support may reduce the excess of psychosis in migrants.