Introduction Evidence from observational and genetic studies suggests a bidirectional relationship between loneliness and psychosis. To our knowledge, no previous study has assessed the association between loneliness in childhood and first-episode psychosis (FEP). Objectives We aimed to assess the association between loneliness in childhood and the odds of FEP and clinical variables of interest (i.e., diagnosis and clinical and functional severity) in FEP and to explore gender differences in this association. Methods This was an observational, case-control study, based on the AGES-CM cohort, a longitudinal prospective study including patients with FEP ages 7-40, their first-degree relatives, and an age- and sex-matched sample of controls in seven university hospitals in the region of Madrid. We assessed loneliness in childhood with the question “Have you ever felt lonely for more than 6 months before the age of 12” and objetive social isolation with the peer relationships item from the childhood subscale of the Premorbid Adjustment Scale. We conducted logistic and linear regression analyses to assess the association between childhood loneliness and i) the odds of presenting a FEP and ii) clinical variables of interest (diagnosis and scores on positive, negative, general, depressive, and manic symptoms and functioning), while adjusting for demographic variables. Results The study sample comprised 285 patients with FEP (32.6% female, age 24.50 ± 6.2 years) and 546 controls (48.7% female, age 25.93 ± 5.5 years). Loneliness in childhood was associated with increased odds of FEP (adjusted odds ratio; aOR: 2.17, 95% CI [1.40-3.51], p=.002). This association remained significant after controlling for objective social isolation in childhood (aOR:2.70, IC 95% [1.58-4.62], p<.001). The effect of the association was stronger in females (aOR:4.74, 95% CI [2.23-10.05], p<.001) than in males (aOR:1.17, IC 95% [0.63-2.19], p=.623). In females with FEP, loneliness in childhood was significantly associated with increased odds of receiving a diagnosis of other psychosis (aOR:0.155, 95% CI [0.048-0.506], p=.002) relative to an SSD diagnosis. In the FEP sample, loneliness in childhood was associated with greater severity of positive and affective symptoms and worse functioning. Conclusions Loneliness in childhood is associated with increased odds of FEP and clinical variables of interest. This suggests the potential role of this phenotype as an early risk marker for psychosis that could help guide targeted interventions. Disclosure of Interest C. Díaz-Caneja Grant / Research support from: Instituto de Salud Carlos III (PI17/00481, PI20/00721, JR19/00024), European Union, Consultant of: Angelini, L. Donaire: None Declared, V. Cavone: None Declared, Á. Andreu-Bernabeu: None Declared, J. González-Peñas: None Declared, M. Díaz-Marsá: None Declared, R. Rodríguez-Jiménez: None Declared, Á. Ibáñez: None Declared, E. Baca-García: None Declared, J. C. Leza: None Declared, M. F. Bravo-Ortiz: None Declared, J. L. Ayuso-Mateos: None Declared, C. Arango Grant / Research support from: Madrid Regional Government (R&D activities in Biomedicine S2022/BMD-7216 AGES 3-CM), Instituto de Salud Carlos III, European Union, Consultant of: Acadia, Angelini, Biogen, Boehringer, Gedeon Richter, Janssen Cilag, Lundbeck, Medscape, Menarini, Minerva, Otsuka, Pfizer, Roche, Sage, Servier, Shire, Schering Plough, Sumitomo Dainippon Pharma, Sunovion and Takeda

INTRODUCTION:Suicidal ideation is common among individuals with first episode psychosis (FEP), with prevalence estimates up to 56.5 %. Despite its high prevalence, relatively little is known about how sociodemographic, clinical and/or developmental characteristics contribute to the experience of suicidal ideation in individuals with FEP. METHODS:In this cross-sectional study (FEP n = 551 and controls n = 857), univariate logistic regression analyses were performed to study the associations of sociodemographic, clinical, and developmental factors with suicidal ideation in individuals with FEP as well as controls. Suicidal ideation was assessed using the Community Assessment of Psychic Experiences (CAPE). In addition, multivariate logistic regression analyses were conducted based on a stepwise approach. RESULTS:In FEP, only depressive symptoms remained significantly associated with suicidal ideation when all correlates were integrated into one model. In the multivariate model in controls, depressive symptoms, positive symptoms, and traumatic childhood experiences were significantly associated with suicidal ideation. CONCLUSIONS:This study showed that depressive symptoms are an important factor relating to suicidal ideation in individuals with FEP, over and above other clinical, sociodemographic, and developmental factors. This underscores the relevance of screening for suicidal ideation in individuals with FEP, and highlights the need for a better understanding of the diagnostic uncertainty and course of mood symptoms in early psychosis. LIMITATIONS:Cross-sectional study design, self-reported questionnaires.

Background We examined whether cannabis use contributes to the increased risk of psychotic disorder for non-western minorities in Europe.Methods We used data from the EU-GEI study (collected at sites in Spain, Italy, France, the United Kingdom, and the Netherlands) on 825 first-episode patients and 1026 controls. We estimated the odds ratio (OR) of psychotic disorder for several groups of migrants compared with the local reference population, without and with adjustment for measures of cannabis use.Results The OR of psychotic disorder for non-western minorities, adjusted for age, sex, and recruitment area, was 1.80 (95% CI 1.39-2.33). Further adjustment of this OR for frequency of cannabis use had a minimal effect: OR = 1.81 (95% CI 1.38-2.37). The same applied to adjustment for frequency of use of high-potency cannabis. Likewise, adjustments of ORs for most sub-groups of non-western countries had a minimal effect. There were two exceptions. For the Black Caribbean group in London, after adjustment for frequency of use of high-potency cannabis the OR decreased from 2.45 (95% CI 1.25-4.79) to 1.61 (95% CI 0.74-3.51). Similarly, the OR for Surinamese and Dutch Antillean individuals in Amsterdam decreased after adjustment for daily use: from 2.57 (95% CI 1.07-6.15) to 1.67 (95% CI 0.62-4.53).Conclusions The contribution of cannabis use to the excess risk of psychotic disorder for non-western minorities was small. However, some evidence of an effect was found for people of Black Caribbean heritage in London and for those of Surinamese and Dutch Antillean heritage in Amsterdam.

Background. Cannabis use and familial vulnerability to psychosis have been associated with social cognition deficits. This study examined the potential relationship between cannabis use and cognitive biases underlying social cognition and functioning in patients with first episode psychosis (FEP), their siblings, and controls. Methods. We analyzed a sample of 543 participants with FEP, 203 siblings, and 1168 controls from the EU-GEI study using a correlational design. We used logistic regression analyses to examine the influence of clinical group, lifetime cannabis use frequency, and potency of cannabis use on cognitive biases, accounting for demographic and cognitive variables. Results. FEP patients showed increased odds of facial recognition processing (FRP) deficits (OR = 1.642, CI 1.123-2.402) relative to controls but not of speech illusions (SI) or jumping to conclusions (JTC) bias, with no statistically significant differences relative to siblings. Daily and occasional lifetime cannabis use were associated with decreased odds of SI (OR = 0.605, CI 0.368-0.997 and OR = 0.646, CI 0.457-0.913 respectively) and JTC bias (OR = 0.625, CI 0.422-0.925 and OR = 0.602, CI 0.460-0.787 respectively) compared with lifetime abstinence, but not with FRP deficits, in the whole sample. Within the cannabis user group, low-potency cannabis use was associated with increased odds of SI (OR = 1.829, CI 1.297-2.578, FRP deficits (OR = 1.393, CI 1.031-1.882, and JTC (OR = 1.661, CI 1.271-2.171) relative to high-potency cannabis use, with comparable effects in the three clinical groups. Conclusions. Our findings suggest increased odds of cognitive biases in FEP patients who have never used cannabis and in low-potency users. Future studies should elucidate this association and its potential implications.

Only a small number of studies have assessed structural differences between the two hemispheres during childhood and adolescence. However, the existing findings lack consistency or are restricted to a particular brain region, a specific brain feature, or a relatively narrow age range. Here, we investigated associations between brain asymmetry and age as well as sex in one of the largest pediatric samples to date (n = 4265), aged 1-18 years, scanned at 69 sites participating in the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) consortium. Our study revealed that significant brain asymmetries already exist in childhood, but their magnitude and direction depend on the brain region examined and the morphometric measurement used (cortical volume or thickness, regional surface area, or subcortical volume). With respect to effects of age, some asymmetries became weaker over time while others became stronger; sometimes they even reversed direction. With respect to sex differences, the total number of regions exhibiting significant asymmetries was larger in females than in males, while the total number of measurements indicating significant asymmetries was larger in males (as we obtained more than one measurement per cortical region). The magnitude of the significant asymmetries was also greater in males. However, effect sizes for both age effects and sex differences were small. Taken together, these findings suggest that cerebral asymmetries are an inherent organizational pattern of the brain that manifests early in life. Overall, brain asymmetry appears to be relatively stable throughout childhood and adolescence, with some differential effects in males and females.

Abstract Introduction People with mental health disorders (MHDs) have worse physical health compared to the general population. To date, no comprehensive epidemiological overview exists and the extent of the excess public health burden is unknown. Our aim was to estimate the prevalence of excess PHC diagnoses associated with MHDs in the European working-age population. Methods We estimated excess PHC diagnoses associated with depressive disorders (DD), bipolar disorder (BD), schizophrenia (SZ), and alcohol use disorders (AUD) for year 2019. Levels of excess risks for PHCs were identified by a structured literature review and synthesised per MHD and categories of PHCs using random-effects meta-analyses. Estimated relative risks (RRs) were combined with country-level disease prevalence and population data to calculate population attributable fractions (PAFs). Based on obtained PAFs we calculated excess PHC diagnoses due to underlying MHDs for all EU-27 member states, Iceland, Liechtenstein, Norway, Switzerland, and the United Kingdom. Results We identified 72 studies for estimating excess levels of risk for PHCs, focused on DD (n = 29, 40%), SZ (n = 26, 36%), BD (n = 9, 13%), AUD (n = 4, 6%), or multiple MHDs (n = 4, 6%). Estimated RRs ranged from 1.3 to 1.8 (DD), from 1.8 to 15.8 (BD), from 1.5 to 4.0 (SZ), and from 1.9 to 3.3 (AUD). Corresponding excess PHC diagnoses in the total European working-age population (312.5 million) were 24.6 million (AUD), 12.6 million (DD), 6.6 million (BD), and 0.9 million (SZ). Discussion This is the first comprehensive estimation of the public health burden of excess PHCs associated with DD, BD, SZ, and AUD in the European working-age population. Our results unequivocally demonstrate broader population health benefits of investments into integrated mental and physical healthcare. Targeted policies should consider prevention strategies as sustainable and equitable approaches to alleviate substantial physical health disparities in people with MHDs. Key messages • Working-age individuals with mental health disorders in Europe suffer from substantial physical health disparities in nearly all physical health areas. • Integrated mental and physical healthcare, and prevention strategies are equitable and sustainable approaches to reduce these physical health disparities.

AbstractBackgroundTobacco is a highly prevalent substance of abuse in patients with psychosis. Previous studies have reported an association between tobacco use and schizophrenia. The aim of this study was to analyze the relationship between tobacco use and first-episode psychosis (FEP), age at onset of psychosis, and specific diagnosis of psychosis.MethodsThe sample consisted of 1105 FEP patients and 1355 controls from the European Network of National Schizophrenia Networks Studying Gene–Environment Interactions (EU-GEI) study. We assessed substance use with the Tobacco and Alcohol Questionnaire and performed a series of regression analyses using case-control status, age of onset of psychosis, and diagnosis as outcomes and tobacco use and frequency of tobacco use as predictors. Analyses were adjusted for sociodemographic characteristics, alcohol, and cannabis use.ResultsAfter controlling for cannabis use, FEP patients were 2.6 times more likely to use tobacco [p ⩽ 0.001; adjusted odds ratio (AOR) 2.6; 95% confidence interval (CI) [2.1–3.2]] and 1.7 times more likely to smoke 20 or more cigarettes a day (p = 0.003; AOR 1.7; 95% CI [1.2–2.4]) than controls. Tobacco use was associated with an earlier age at psychosis onset (β = −2.3; p ⩽ 0.001; 95% CI [−3.7 to −0.9]) and was 1.3 times more frequent in FEP patients with a diagnosis of schizophrenia than in other diagnoses of psychosis (AOR 1.3; 95% CI [1.0–1.8]); however, these results were no longer significant after controlling for cannabis use.ConclusionsTobacco and heavy-tobacco use are associated with increased odds of FEP. These findings further support the relevance of tobacco prevention in young populations.

Introduction The Positive and Negative Syndrome Scale for Schizophrenia Autism Severity Scale (PAUSS) scale can be derived from the Positive and Negative Schizophrenia Syndrome Scale, enabling an assessment of psychotic and autistic dimensions with a single tool. Objectives The aim of the study was to investigate the prevalence of autistic traits and the diagnostic, developmental, clinical, and functional correlates of this phenotype in a sample of early-onset psychosis (onset before age 18 years; EOP). Methods Prospective observational 2 year- follow-up study in a sample of young people with a first-episode of EOP. Demographic, perinatal, developmental, cognitive, clinical, and functional data were collected. PAUSS total scores and socio-communication and repetitive behaviors subscores were calculated. We used the proposed cut-off points for adult populations to define prevalence of autistic traits (PAUSS≥30). Subgroups of patients with and without autistic traits were identified based on the total PAUSS terciles. We used the Cronbach’s alpha test to assess the PAUSS internal consistency. Linear mixed models were performed to compare changes in PAUSS during follow-up between diagnostic subgroups [i.e., non-affective psychosis (including schizophrenia and schizophreniform disorder), affective psychosis (including bipolar disorder, schizoaffective disorder and major depressive disorder with psychotic features), and other psychosis (including brief psychotic disorder and psychosis not otherwise specified)]. Developmental, clinical, and functional variables were compared between subgroups with and without autistic traits with logistic regression analysis. Results 248 patients with PIT were included (age 15.69 ± 1.86 years, 38.65% female). The prevalence of autistic traits in EOP was 7.04%, with significantly higher prevalence in the group of patients with non-affective psychosis (15.20%) than in other diagnostic groups. PAUSS scores significantly decreased over time, with no significant differences in the trajectories of the total PAUSS and its subscores among the three diagnostic subgroups during the 2-year follow-up. The PAUSS showed good internal consistency at all visits (Cronbach’s alpha > 0,88). Patients with autistic traits presented longer duration of untreated psychosis, longer duration of the first inpatient admission, poorer social adjustment in childhood, poorer functionality, greater clinical severity, and poorer response to treatment during follow-up than patients without autistic traits. Conclusions The PAUSS is an easy-to-apply tool that can be useful to differentiate psychosis subgroups with worse prognosis. Disclosure of Interest J. Suárez Campayo: None Declared, L. Pina-Camacho: None Declared, J. Merchán-Naranjo: None Declared, C. Ordas: None Declared, V. Cavone: None Declared, R. Panadero: None Declared, G. Sugranyes: None Declared, I. Baeza: None Declared, J. Castro-Fornieles: None Declared, E. de la Serna: None Declared, C. Arango Consultant of: Acadia, Angelini, Gedeon Richter, Janssen Cilag, Lundbeck, Minerva, Otsuka, Roche, Sage, Servier, Shire, Schering Plough, Sumitomo Dainippon Pharma, Sunovion and Takeda, C. Diaz Caneja Grant / Research support from: Exeltis and Angelini