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Psychotic experiences (PE) are prevalent in general and clinical populations and can increase the risk for mental disorders in young people. The Community Assessment of Psychic Experiences (CAPE) is a widely used measure to assess PE in different populations and settings. However, the current knowledge on their overall reliability is limited. We examined the reliability of the CAPE-42 and later versions, testing the role of age, sex, test scores, and clinical status as moderators. A systematic search was conducted on the Scopus, Web of Science, PubMed, EBSCOhost, ProQuest, and GoogleScholar databases. Internal consistency and temporal stability indices were examined through reliability generalization meta-analysis (RGMA). Moderators were tested through meta-regression analysis. From a pool of 1,015 records, 90 independent samples were extracted from 71 studies. Four versions showed quantitative evidence for inclusion: CAPE-42, CAPE-20, CAPE-P15, and CAPE-P8. Internal consistency indices were good (α/ω≈.725-0.917). Temporal stability was only analyzed for the CAPE-P15, yielding a moderate but not-significant effect (r=0.672). The evidence for temporal stability is scant due to the limited literature, and definitive conclusions cannot be drawn. Further evidence on other potential moderators such as adverse experiences or psychosocial functioning is required.

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BACKGROUND: Incidence of first-episode psychosis (FEP) varies substantially across geographic regions. Phenotypes of subclinical psychosis (SP), such as psychotic-like experiences (PLEs) and schizotypy, present several similarities with psychosis. We aimed to examine whether SP measures varied across different sites and whether this variation was comparable with FEP incidence within the same areas. We further examined contribution of environmental and genetic factors to SP. METHODS: We used data from 1497 controls recruited in 16 different sites across 6 countries. Factor scores for several psychopathological dimensions of schizotypy and PLEs were obtained using multidimensional item response theory models. Variation of these scores was assessed using multi-level regression analysis to estimate individual and between-sites variance adjusting for age, sex, education, migrant, employment and relational status, childhood adversity, and cannabis use. In the final model we added local FEP incidence as a second-level variable. Association with genetic liability was examined separately. RESULTS: Schizotypy showed a large between-sites variation with up to 15% of variance attributable to site-level characteristics. Adding local FEP incidence to the model considerably reduced the between-sites unexplained schizotypy variance. PLEs did not show as much variation. Overall, SP was associated with younger age, migrant, unmarried, unemployed and less educated individuals, cannabis use, and childhood adversity. Both phenotypes were associated with genetic liability to schizophrenia. CONCLUSIONS: Schizotypy showed substantial between-sites variation, being more represented in areas where FEP incidence is higher. This supports the hypothesis that shared contextual factors shape the between-sites variation of psychosis across the spectrum.

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Background: Depressive disorder is one of the leading causes of disability worldwide; however its prevalence and association with inequality and crime is poorly characterised in Latin America. This study aimed to: i. systematically review population-based studies of prevalence of ICD/DSM depressive disorder in Latin America, ii. report pooled regional, country, and sex-specific prevalence estimates, and iii. test its association with four country-level development indicators: human development (HDI), income (Gini) and gender inequality (GII), and intentional homicide rate (IHR). Methods: We conducted a systematic review and meta-analysis of population-based studies reporting primary data on the prevalence of ICD/DSM depressive disorder in Latin America from 1990 to 2023, irrespective of language. We searched PubMed, PsycINFO, Cochrane Library, SciELO (regional database), LILAC (regional database), and available grey literature. Study quality was assessed using JBI's critical appraisal tools. We generated pooled estimates using random-effects meta-analysis; heterogeneity was assessed using the I2 statistic. Meta-regression analyses were used to test associations of depression prevalence with indicators of inequality and human development. The study was registered with PROSPERO (CRD42019143054). Findings: Using data from 40 studies in Latin America, lifetime, 12-month, and current prevalence of ICD/DSM depressive disorder were calculated at 12.58% (95% CI 11.00%-14.16%); 5.30% (4.55-6.06%), and 3.12% (2.22-4.03), respectively. Heterogeneity was high across lifetime, 12-month, and current prevalence, sex, and countries. 12-month and current prevalence was associated with higher Gini and GII, 12-month prevalence with lower HDI, and current prevalence with higher IHR. Interpretation: We found a high prevalence of ICD/DSM depressive disorders in Latin America, and a statistically significant association with inequality and development indicators. The high heterogeneity found across prevalence periods and the major gaps in country representation underscore the need to escalate efforts to improve mental health access and research capabilities in Latin America. Systematic, comparable prevalence estimates would inform more effective decision-making in the region. Funding: Pfizer Independent Medical Education Grant.

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BACKGROUND: The Inner Santiago Health Study (ISHS) aimed to (i) estimate the prevalence of common mental disorders (CMD; i.e. depressive and anxiety disorders) among immigrants of Peruvian origin in Chile; (ii) determine whether such immigrants are at higher risk of CMD when compared with the native-born geographically matched population (i.e. non-immigrants); and (iii) identify factors associated with higher risk of any CMD among this immigrant group. A secondary aim was to describe access to mental health services by Peruvian immigrants meeting criteria for any CMD. METHODS: Findings are based on a population-based cross-sectional household mental health survey of 608 immigrant and 656 non-immigrant adults (18-64 years) residing in Santiago de Chile. Diagnoses of ICD-10 depressive and anxiety disorders and of any CMD were obtained using the Revised Clinical Interview Schedule. The relationships between demographic, economic, psychosocial, and migration-specific predictor variables, and risk of any CMD were analyzed with a series of stepwise multivariate logistic regression models. RESULTS: The one-week prevalence of any CMD was 29.1% (95% CI: 25.2-33.1) among immigrants and 34.7% (95% CI: 30.7-38.7) among non-immigrants. Depending on the statistical model used in the pooled sample, we found the prevalence of any CMD among non-immigrants to be higher (OR=1.53; 95% CI: 1.05-2.25) or similar (OR=1.34; 95% CI: 0.94-19.2) when compared with immigrants. In the multivariate stepwise regression of any CMD in immigrants only, the prevalence was higher for females, those with primary compared to higher education, in debt and exposed to discrimination. Conversely, higher levels of functional social support, sense of comprehensibility, and manageability were associated with a lower risk of any CMD in immigrants. In addition, no differences were observed between immigrants and non-immigrants reporting any CMD in mental health service utilization. CONCLUSION: Our results evidence high levels of current CMD in this immigrant group, particularly amongst women. However, lower adjusted prevalence of any CMD in immigrants compared to non-immigrants was limited to preliminary statistical models, thus failing to provide clear support for a "healthy immigrant effect". The study sheds new light on differences in CMD prevalence by immigrant status in Latin America by examining differential exposure to risk factors in immigrant versus non-immigrant groups.

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

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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.

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BACKGROUND: Cannabis use is associated with increased risk of later psychotic disorder but whether it affects incidence of the disorder remains unclear. We aimed to identify patterns of cannabis use with the strongest effect on odds of psychotic disorder across Europe and explore whether differences in such patterns contribute to variations in the incidence rates of psychotic disorder. METHODS: We included patients aged 18-64 years who presented to psychiatric services in 11 sites across Europe and Brazil with first-episode psychosis and recruited controls representative of the local populations. We applied adjusted logistic regression models to the data to estimate which patterns of cannabis use carried the highest odds for psychotic disorder. Using Europe-wide and national data on the expected concentration of Δ9-tetrahydrocannabinol (THC) in the different types of cannabis available across the sites, we divided the types of cannabis used by participants into two categories: low potency (THC <10%) and high potency (THC ≥10%). Assuming causality, we calculated the population attributable fractions (PAFs) for the patterns of cannabis use associated with the highest odds of psychosis and the correlation between such patterns and the incidence rates for psychotic disorder across the study sites. FINDINGS: Between May 1, 2010, and April 1, 2015, we obtained data from 901 patients with first-episode psychosis across 11 sites and 1237 population controls from those same sites. Daily cannabis use was associated with increased odds of psychotic disorder compared with never users (adjusted odds ratio [OR] 3·2, 95% CI 2·2-4·1), increasing to nearly five-times increased odds for daily use of high-potency types of cannabis (4·8, 2·5-6·3). The PAFs calculated indicated that if high-potency cannabis were no longer available, 12·2% (95% CI 3·0-16·1) of cases of first-episode psychosis could be prevented across the 11 sites, rising to 30·3% (15·2-40·0) in London and 50·3% (27·4-66·0) in Amsterdam. The adjusted incident rates for psychotic disorder were positively correlated with the prevalence in controls across the 11 sites of use of high-potency cannabis (r = 0·7; p=0·0286) and daily use (r = 0·8; p=0·0109). INTERPRETATION: Differences in frequency of daily cannabis use and in use of high-potency cannabis contributed to the striking variation in the incidence of psychotic disorder across the 11 studied sites. Given the increasing availability of high-potency cannabis, this has important implications for public health. FUNDING SOURCE: Medical Research Council, the European Community's Seventh Framework Program grant, São Paulo Research Foundation, National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust and King's College London and the NIHR BRC at University College London, Wellcome Trust.

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Importance: Psychotic disorders contribute significantly to the global disease burden, yet the latest international incidence study of psychotic disorders was conducted in the 1980s. Objectives: To estimate the incidence of psychotic disorders using comparable methods across 17 catchment areas in 6 countries and to examine the variance between catchment areas by putative environmental risk factors. Design, Setting, and Participants: An international multisite incidence study (the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions) was conducted from May 1, 2010, to April 1, 2015, among 2774 individuals from England (2 catchment areas), France (3 catchment areas), Italy (3 catchment areas), the Netherlands (2 catchment areas), Spain (6 catchment areas), and Brazil (1 catchment area) with a first episode of nonorganic psychotic disorders (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] codes F20-F33) confirmed by the Operational Criteria Checklist. Denominator populations were estimated using official national statistics. Exposures: Age, sex, and racial/ethnic minority status were treated as a priori confounders. Latitude, population density, percentage unemployment, owner-occupied housing, and single-person households were treated as catchment area-level exposures. Main Outcomes and Measures: Incidence of nonorganic psychotic disorders (ICD-10 codes F20-F33), nonaffective psychoses (ICD-10 codes F20-F29), and affective psychoses (ICD-10 codes F30-F33) confirmed by the Operational Criteria Checklist. Results: A total of 2774 patients (1196 women and 1578 men; median age, 30.5 years [interquartile range, 23.0-41.0 years]) with incident cases of psychotic disorders were identified during 12.9 million person-years at risk (crude incidence, 21.4 per 100 000 person-years; 95% CI, 19.4-23.4 per 100 000 person-years). A total of 2183 patients (78.7%) had nonaffective psychotic disorders. After direct standardization for age, sex, and racial/ethnic minority status, an 8-fold variation was seen in the incidence of all psychotic disorders, from 6.0 (95% CI, 3.5-8.6) per 100 000 person-years in Santiago, Spain, to 46.1 (95% CI, 37.3-55.0) per 100 000 person-years in Paris, France. Rates were elevated in racial/ethnic minority groups (incidence rate ratio, 1.6; 95% CI, 1.5-1.7), were highest for men 18 to 24 years of age, and were lower in catchment areas with more owner-occupied homes (incidence rate ratio, 0.8; 95% CI, 0.7-0.8). Similar patterns were observed for nonaffective psychoses; a lower incidence of affective psychoses was associated with higher area-level unemployment (incidence rate ratio, 0.3; 95% CI, 0.2-0.5). Conclusions and Relevance: This study confirmed marked heterogeneity in risk for psychotic disorders by person and place, including higher rates in younger men, racial/ethnic minorities, and areas characterized by a lower percentage of owner-occupied houses.

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BACKGROUND: Childhood adversity has been associated with onset of psychosis in adulthood but these studies have used only general definitions of this environmental risk indicator. Therefore, we sought to explore the prevalence of more specific adverse childhood experiences amongst those with and without psychotic disorders using detailed assessments in a large epidemiological case-control sample (AESOP). METHOD: Data were collected on 182 first-presentation psychosis cases and 246 geographically matched controls in two UK centres. Information relating to the timing and frequency of exposure to different types of childhood adversity (neglect, antipathy, physical and sexual abuse, local authority care, disrupted living arrangements and lack of supportive figure) was obtained using the Childhood Experience of Care and Abuse Questionnaire. RESULTS: Psychosis cases were three times more likely to report severe physical abuse from the mother that commenced prior to 12 years of age, even after adjustment for other significant forms of adversity and demographic confounders. A non-significant trend was also evident for greater prevalence of reported severe maternal antipathy amongst those with psychosis. Associations with maternal neglect and childhood sexual abuse disappeared after adjusting for maternal physical abuse and antipathy. Paternal maltreatment and other forms of adversity were not associated with psychosis nor was there evidence of a dose-response effect. CONCLUSIONS: These findings suggest that only specific adverse childhood experiences are associated with psychotic disorders and only in a minority of cases. If replicated, this greater precision will ensure that research into the mechanisms underlying the pathway from childhood adversity to psychosis is more fruitful.

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BACKGROUND: Several studies have suggested that neuropsychological and structural brain deficits are implicated in poor insight. Few insight studies however have combined neurocognitive and structural neuroanatomical measures. AIMS: Focusing on the ability to relabel psychotic symptoms as pathological, we examined insight, brain structure and neurocognition in first-onset psychosis.METHOD: Voxel-based magnetic resonance imaging data were acquired from 82 individuals with psychosis and 91 controls assessed with a brief neuropsychological test battery. Insight was measured using the Schedule for the Assessment of Insight. RESULTS: The principal analysis showed reduced general neuropsychological function was linked to poor symptom relabelling ability. A subsequent between-psychosis group analysis found those with no symptom relabelling ability had significant global and regional grey matter deficits primarily located at the posterior cingulate gyrus and right precuneus/cuneus. CONCLUSIONS: The cingulate gyrus (as part of a midline cortical system) along with right hemisphere regions may be involved in illness and symptom self-appraisal in first-onset psychosis.

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BACKGROUND: It remains unclear if the excess of neurological soft signs, or of certain types of neurological soft signs, is common to all psychoses, and whether this excess is simply an epiphenomenon of the lower general cognitive ability present in psychosis. AIMS: To investigate whether an excess of neurological soft signs is independent of diagnosis (schizophrenia v. affective psychosis) and cognitive ability (IQ). METHOD: Evaluation of types of neurological soft signs in a prospective cohort of all individuals presenting with psychoses over 2 years (n=310), and in a control group from the general population (n=239). RESULTS: Primary (P<0.001), motor coordination (P<0.001), and motor sequencing (P<0.001) sign scores were significantly higher in people with any psychosis than in the control group. However, only primary and motor coordination scores remained higher when individuals with psychosis and controls were matched for premorbid and current IQ. CONCLUSIONS: Higher rates of primary and motor coordination signs are not associated with lower cognitive ability, and are specific to the presence of psychosis.

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BACKGROUND: Grey matter and other structural brain abnormalities are consistently reported in first-onset schizophrenia, but less is known about the extent of neuroanatomical changes in first-onset affective psychosis. AIMS: To determine which brain abnormalities are specific to (a) schizophrenia and (b) affective psychosis. METHOD: We obtained dual-echo (proton density/T2-weighted) magnetic resonance images and carried out voxel-based analysis on the images of 73 patients with first-episode psychosis (schizophrenia n=44, affective psychosis n=29) and 58 healthy controls. RESULTS: Both patients with schizophrenia and patients with affective psychosis had enlarged lateral and third ventricle volumes. Regional cortical grey matter reductions (including bilateral anterior cingulate gyrus, left insula and left fusiform gyrus) were evident in affective psychosis but not in schizophrenia, although patients with schizophrenia displayed decreased hippocampal grey matter and increased striatal grey matter at a more liberal statistical threshold. CONCLUSIONS: Both schizophrenia and affective psychosis are associated with volumetric abnormalities at the onset of frank psychosis, with some of these evident in common brain areas.

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CONTEXT Convention suggests uniformity of incidence of schizophrenia and other psychoses; variation would have implications for their causes and biological characteristics. OBJECTIVE To investigate variability in the incidence of psychotic syndromes in terms of place, ethnicity, age, and sex. DESIGN Three-center, prospective, comprehensive survey of clinically relevant first-onset psychotic syndromes over a 2-year period (1997-1999). Census data provided the denominator. SETTING Southeast London, Nottingham, and Bristol, England. PARTICIPANTS One million six hundred thousand person-years yielded 568 subjects aged 16 to 64 years with clinically relevant psychotic syndromes. MAIN OUTCOME MEASURES The World Health Organization Psychosis Screen and the Schedules for Clinical Assessment in Neuropsychiatry to classify, blind to ethnicity, all DSM-IV psychotic syndromes and the subclasses of schizophrenia, other nonaffective disorders, affective disorders, and substance-induced psychosis.

RESULTS All syndromes showed a characteristic age distribution. Schizophrenia was significantly more common in men (incidence rate ratio [IRR], 2.3 [95% confidence interval (CI), 1.7-3.1]); affective disorders occurred equally in men and women (IRR, 1.0 [95% CI, 0.7-1.3]). All psychoses were more common in the black and minority ethnic group (crude IRR, 3.6 [95% CI, 3.0-4.2]). Differences in age, sex, and study center accounted for approximately a quarter of this effect (adjusted IRR, 2.9 [95% CI, 2.4-3.5]) in each psychosis outcome. The age-sex standardized incidence rate for all psychoses was higher in Southeast London (IRR, 49.4 [95% CI, 43.6-55.3]) than Nottingham (IRR, 23.9 [95% CI, 20.6-27.2]) or Bristol (IRR, 20.4 [95% CI, 15.1-25.7]). Rates of all outcomes except affective disorders remained significantly higher in Southeast London when the model was expanded to control for ethnicity. CONCLUSIONS There is significant and independent variation of incidence of schizophrenia and other psychoses in terms of sex, age, ethnicity, and place. This confirms that environmental effects at the individual, and perhaps neighborhood level, may interact together and with genetic factors in the etiology of psychosis.

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Subjects at their first psychotic episode show an enlarged volume of the pituitary gland, but whether this is due to hypothalamic–pituitary–adrenal (HPA) axis hyperactivity, or to stimulation of the prolactin-secreting cells by antipsychotic treatment, is unclear. We measured pituitary volume, using 1.5-mm, coronal, 1.5 T, high-resolution MRI images, in 78 patients at the first psychotic episode and 78age- and gender-matched healthy controls. In all, 18 patients were antipsychotic-free (12 of these were antipsychotic-naý¨ve), 26 werereceiving atypical antipsychotics, and 33 were receiving typical antipsychotics. As hypothesized, patients had a larger pituitary volume than controls (+22percent , p=0.001). When divided by antipsychotic treatment, and compared to controls, the pituitary volume was 15 percent larger in antipsychotic-free patients (p¼0.028), 17 percent larger in patients receiving atypicals (p¼0.01), and 30 percent larger in patients receiving typicals (p=0.001). Patients receiving typicals not only had the largest pituitary volume compared to controls but also showed a trend for a larger pituitary volume compared to the other patients grouped together (11 percent, p¼0.08). When divided by diagnosis, and compared to controls, the pituitary volume was 24 percent larger in patients with schizophrenia/schizophreniform disorder (n¼40, p=0.001), 19 percent larger in depressed patients (n¼13, p¼0.022), 16 percent larger in bipolar patients (n¼16, p¼0.037), and 12 percent larger in those with other psychoses (n¼9, p¼0.2). In conclusion, the first-episode of a psychotic disorder is associated with a larger pituitary independently of the presenceof antipsychotic treatment, and this could be due to activation of the HPA axis. Typical antipsychotics exert an additional enlarging effecton pituitary volume, likely to be related to activation of prolactin-secreting cells...

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Patients with schizophrenia and related psychoses have an excess of minor neurological abnormalities (neurological soft signs of unclear neuropathological origin. These include poor motor coordination, sensory perceptual difficulties and difficulties in sequencing complex motor tasks. Neurological soft signs seem not to reflect primary tract or nuclear pathology. It still has to be established whether neurological soft signs result from specific or diffuse brain structural abnormalities. Studying their anatomical correlates can provide not only a better understanding of the aetiopathogenesis of soft signs, but also of the pathophysiology of schizophrenia. Suprisingly few studies have investigated the brain correlates of neurological soft signs. In the present study, we investigated the relationship between brain structure and neurological soft signs in an epidemiologically based sample of 77 first-episode psychosis patients. We used the Neurological Evaluation Scale for neurological assessment and high-resolution MRI and voxel based methods of image analysis to investigate brain structure. Higher rates of soft neurological signs (both motor and sensory) were associated with a reduction of grey matter volume of subcortical structures (putamen, globus pallidus and thalamus). Signs of sensory integration deficits were additionally associated with volume reduction in the cerebral cortex, including the precentral, superior and middle temporal, and lingual gyri. Neurological soft signs and their associated brain changes were independent of antipsychotic exposure. We conclude that neurological soft signs are associated with regional grey matter volume changes and that they may represent a clinical sign of the perturbed cortical-subcortical connectivity that putatively underlies psychotic disorders(AU)

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