The association between cannabis and psychosis is established, but the role of underlying genetics is unclear. We used data from the EU-GEI case-control study and UK Biobank to examine the independent and combined effect of heavy cannabis use and schizophrenia polygenic risk score (PRS) on risk for psychosis.

Genome-wide association study summary statistics from the Psychiatric Genomics Consortium and the Genomic Psychiatry Cohort were used to calculate schizophrenia and cannabis use disorder (CUD) PRS for 1098 participants from the EU-GEI study and 143600 from the UK Biobank. Both datasets had information on cannabis use.

In both samples, schizophrenia PRS and cannabis use independently increased risk of psychosis. Schizophrenia PRS was not associated with patterns of cannabis use in the EU-GEI cases or controls or UK Biobank cases. It was associated with lifetime and daily cannabis use among UK Biobank participants without psychosis, but the effect was substantially reduced when CUD PRS was included in the model. In the EU-GEI sample, regular users of high-potency cannabis had the highest odds of being a case independently of schizophrenia PRS (OR daily use high-potency cannabis adjusted for PRS = 5.09, 95% CI 3.08–8.43, p = 3.21 × 10−10). We found no evidence of interaction between schizophrenia PRS and patterns of cannabis use.

Regular use of high-potency cannabis remains a strong predictor of psychotic disorder independently of schizophrenia PRS, which does not seem to be associated with heavy cannabis use. These are important findings at a time of increasing use and potency of cannabis worldwide.

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.

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.

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.

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.

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).

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.

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.

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.

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.

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

We examined whether cannabis use contributes to the increased risk of psychotic disorder for non-western minorities in Europe.

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.

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).

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.

Little is known about when youth may be at greatest risk for attempting suicide, which is critically important information for the parents, caregivers, and professionals who care for youth at risk. This study used adolescent and parent reports, and a case-crossover, within-subject design to identify 24-hour warning signs (WS) for suicide attempts.

Adolescents (N = 1094, ages 13 to 18) with one or more suicide risk factors were enrolled and invited to complete bi-weekly, 8–10 item text message surveys for 18 months. Adolescents who reported a suicide attempt (survey item) were invited to participate in an interview regarding their thoughts, feelings/emotions, and behaviors/events during the 24-hours prior to their attempt (case period) and a prior 24-hour period (control period). Their parents participated in an interview regarding the adolescents’ behaviors/events during these same periods. Adolescent or adolescent and parent interviews were completed for 105 adolescents (81.9% female; 66.7% White, 19.0% Black, 14.3% other).

Both parent and adolescent reports of suicidal communications and withdrawal from social and other activities differentiated case and control periods. Adolescent reports also identified feelings (self-hate, emotional pain, rush of feelings, lower levels of rage toward others), cognitions (suicidal rumination, perceived burdensomeness, anger/hostility), and serious conflict with parents as WS in multi-variable models.

This study identified 24-hour WS in the domains of cognitions, feelings, and behaviors/events, providing an evidence base for the dissemination of information about signs of proximal risk for adolescent suicide attempts.

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.

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).

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.

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.

The PAUSS is an easy-to-apply tool that can be useful to differentiate psychosis subgroups with worse prognosis.

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

Childhood adversity and cannabis use are considered independent risk factors for psychosis, but whether different patterns of cannabis use may be acting as mediator between adversity and psychotic disorders has not yet been explored. The aim of this study is to examine whether cannabis use mediates the relationship between childhood adversity and psychosis.

Data were utilised on 881 first-episode psychosis patients and 1231 controls from the European network of national schizophrenia networks studying Gene–Environment Interactions (EU-GEI) study. Detailed history of cannabis use was collected with the Cannabis Experience Questionnaire. The Childhood Experience of Care and Abuse Questionnaire was used to assess exposure to household discord, sexual, physical or emotional abuse and bullying in two periods: early (0–11 years), and late (12–17 years). A path decomposition method was used to analyse whether the association between childhood adversity and psychosis was mediated by (1) lifetime cannabis use, (2) cannabis potency and (3) frequency of use.

The association between household discord and psychosis was partially mediated by lifetime use of cannabis (indirect effect coef. 0.078, s.e. 0.022, 17%), its potency (indirect effect coef. 0.059, s.e. 0.018, 14%) and by frequency (indirect effect coef. 0.117, s.e. 0.038, 29%). Similar findings were obtained when analyses were restricted to early exposure to household discord.

Harmful patterns of cannabis use mediated the association between specific childhood adversities, like household discord, with later psychosis. Children exposed to particularly challenging environments in their household could benefit from psychosocial interventions aimed at preventing cannabis misuse.

While cannabis use is a well-established risk factor for psychosis, little is known about any association between reasons for first using cannabis (RFUC) and later patterns of use and risk of psychosis.

We used data from 11 sites of the multicentre European Gene-Environment Interaction (EU-GEI) case–control study. 558 first-episode psychosis patients (FEPp) and 567 population controls who had used cannabis and reported their RFUC.

We ran logistic regressions to examine whether RFUC were associated with first-episode psychosis (FEP) case–control status. Path analysis then examined the relationship between RFUC, subsequent patterns of cannabis use, and case–control status.

Controls (86.1%) and FEPp (75.63%) were most likely to report ‘because of friends’ as their most common RFUC. However, 20.1% of FEPp compared to 5.8% of controls reported: ‘to feel better’ as their RFUC (χ2 = 50.97; p < 0.001). RFUC ‘to feel better’ was associated with being a FEPp (OR 1.74; 95% CI 1.03–2.95) while RFUC ‘with friends’ was associated with being a control (OR 0.56; 95% CI 0.37–0.83). The path model indicated an association between RFUC ‘to feel better’ with heavy cannabis use and with FEPp-control status.

Both FEPp and controls usually started using cannabis with their friends, but more patients than controls had begun to use ‘to feel better’. People who reported their reason for first using cannabis to ‘feel better’ were more likely to progress to heavy use and develop a psychotic disorder than those reporting ‘because of friends’.

Tobacco 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.

The 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.

After 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.

Tobacco and heavy-tobacco use are associated with increased odds of FEP. These findings further support the relevance of tobacco prevention in young populations.

Gene x environment (G×E) interactions, i.e. genetic modulation of the sensitivity to environmental factors and/or environmental control of the gene expression, have not been reliably established regarding aetiology of psychotic disorders. Moreover, recent studies have shown associations between the polygenic risk scores for schizophrenia (PRS-SZ) and some risk factors of psychotic disorders, challenging the traditional gene v. environment dichotomy. In the present article, we studied the role of GxE interaction between psychosocial stressors (childhood trauma, stressful life-events, self-reported discrimination experiences and low social capital) and the PRS-SZ on subclinical psychosis in a population-based sample.

Data were drawn from the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study, in which subjects without psychotic disorders were included in six countries. The sample was restricted to European descendant subjects (n = 706). Subclinical dimensions of psychosis (positive, negative, and depressive) were measured by the Community Assessment of Psychic Experiences (CAPE) scale. Associations between the PRS-SZ and the psychosocial stressors were tested. For each dimension, the interactions between genes and environment were assessed using linear models and comparing explained variances of ‘Genetic’ models (solely fitted with PRS-SZ), ‘Environmental’ models (solely fitted with each environmental stressor), ‘Independent’ models (with PRS-SZ and each environmental factor), and ‘Interaction’ models (Independent models plus an interaction term between the PRS-SZ and each environmental factor). Likelihood ration tests (LRT) compared the fit of the different models.

There were no genes-environment associations. PRS-SZ was associated with positive dimensions (β = 0.092, R2 = 7.50%), and most psychosocial stressors were associated with all three subclinical psychotic dimensions (except social capital and positive dimension). Concerning the positive dimension, Independent models fitted better than Environmental and Genetic models. No significant GxE interaction was observed for any dimension.

This study in subjects without psychotic disorders suggests that (i) the aetiological continuum hypothesis could concern particularly the positive dimension of subclinical psychosis, (ii) genetic and environmental factors have independent effects on the level of this positive dimension, (iii) and that interactions between genetic and individual environmental factors could not be identified in this sample.

Online interventions can be a complement to maintain the long-term effectiveness of psychosocial interventions in First Episode Psychosis (FEP) that have already demonstrated their efficacy in the short and medium term (Calvo et al., 2015).

To test the effectiveness of a mobile app–based intervention (Thinkapp) to improve quality of life, functioning and symptomatology, and reduce days of admission and hospitalizations, in young people with FEP.

Fourteen patients with FEP, aged 14–30, recruited from Gregorio Marañón Hospital, Ramón y Cajal Hospital and AMAFE Foundation in Madrid (Spain) received treatment as usual plus a psychoeducational intervention through a mobile app. Changes in dependent variables over the course of the intervention were assessed by means of a battery of clinical tests at baseline, 3-month and 6-month follow-up using a Wilcoxon test.

Of the fourteen patients included, 7 patients completed the 6-month follow-up and 8 completed the 3-month follow-up. There were significant differences in days of admission (p = 0.042) between baseline and 6-month follow-up. No significant results were observed in other clinical variables.

The study provides preliminary data potentially related to the reduction of days of admissions.

No significant relationships.

Autism is a lifelong complex neurodevelopmental condition that affects brain development and behaviour with significant consequences for everyday life (WHO, 2018). Despite its personal, familial and societal impact, there is still a European-wide lack of harmonised guidelines about the support needed from early stages, the most sensitive time to gain positive future outcomes (Berajamo-Martin et al, 2019).

The objectives were: 1. To analyse autistic children care pathway and patient/carer journey in three European countries: Italy, Spain and U.K. 2. To propose policy recommendations on how to improve this pathway.

To identify major barriers and treatment gaps, we conducted a rapid literature review of the care pathway in Europe and a survey aimed at parents or carers of autistic children ages 0 to 18 living in the three countries. The survey gathered information on screening, diagnosis, accessibility and support received before, during and after diagnosis. Members of the working group met to discuss results and propose policy recommendations.

1. Current care pathway analysis showed the following treatment gaps: Long waiting time from first concerns until screening visit and confirmed diagnosis. Delayed or no access to intervention once diagnosis has been confirmed. Overall limited information about autism and how to access early detection services. Overall deficient support to families. 2. Please see Box 1 for our proposed policy recommendations.

Box 1. Policy recommendations

Our findings and recommendations will inform policy harmonisation in Europe to shorten long waiting times, diagnosis process and intervention, and therefore, improve autistic people and their families’ journey experience and quality of life.

No significant relationships.

Disruptive behavior disorders (DBD) are heterogeneous at the clinical and the biological level. Therefore, the aims were to dissect the heterogeneous neurodevelopmental deviations of the affective brain circuitry and provide an integration of these differences across modalities.

We combined two novel approaches. First, normative modeling to map deviations from the typical age-related pattern at the level of the individual of (i) activity during emotion matching and (ii) of anatomical images derived from DBD cases (n = 77) and controls (n = 52) aged 8–18 years from the EU-funded Aggressotype and MATRICS consortia. Second, linked independent component analysis to integrate subject-specific deviations from both modalities.

While cases exhibited on average a higher activity than would be expected for their age during face processing in regions such as the amygdala when compared to controls these positive deviations were widespread at the individual level. A multimodal integration of all functional and anatomical deviations explained 23% of the variance in the clinical DBD phenotype. Most notably, the top marker, encompassing the default mode network (DMN) and subcortical regions such as the amygdala and the striatum, was related to aggression across the whole sample.

Overall increased age-related deviations in the amygdala in DBD suggest a maturational delay, which has to be further validated in future studies. Further, the integration of individual deviation patterns from multiple imaging modalities allowed to dissect some of the heterogeneity of DBD and identified the DMN, the striatum and the amygdala as neural signatures that were associated with aggression.

Schizophrenia (SZ), bipolar disorder (BD) and depression (D) run in families. This susceptibility is partly due to hundreds or thousands of common genetic variants, each conferring a fractional risk. The cumulative effects of the associated variants can be summarised as a polygenic risk score (PRS). Using data from the EUropean Network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) first episode case–control study, we aimed to test whether PRSs for three major psychiatric disorders (SZ, BD, D) and for intelligent quotient (IQ) as a neurodevelopmental proxy, can discriminate affective psychosis (AP) from schizophrenia-spectrum disorder (SSD).

Participants (842 cases, 1284 controls) from 16 European EU-GEI sites were successfully genotyped following standard quality control procedures. The sample was stratified based on genomic ancestry and analyses were done only on the subsample representing the European population (573 cases, 1005 controls). Using PRS for SZ, BD, D, and IQ built from the latest available summary statistics, we performed simple or multinomial logistic regression models adjusted for 10 principal components for the different clinical comparisons.

In case–control comparisons PRS-SZ, PRS-BD and PRS-D distributed differentially across psychotic subcategories. In case–case comparisons, both PRS-SZ [odds ratio (OR) = 0.7, 95% confidence interval (CI) 0.54–0.92] and PRS-D (OR = 1.31, 95% CI 1.06–1.61) differentiated AP from SSD; and within AP categories, only PRS-SZ differentiated BD from psychotic depression (OR = 2.14, 95% CI 1.23–3.74).

Combining PRS for severe psychiatric disorders in prediction models for psychosis phenotypes can increase discriminative ability and improve our understanding of these phenotypes. Our results point towards the potential usefulness of PRSs in specific populations such as high-risk or early psychosis phases.

Prof Mucci has been a consultant and/or advisor to or has received honoraria from Gedeon Richter Bulgaria, Janssen Pharmaceuticals, Lundbeck, Otsuka, Pfizer and Pierre Fabre.

Social cognition has been associated with functional outcome in patients with first episode psychosis (FEP). Social cognition has also been associated with neurocognition and cognitive reserve. Although cognitive reserve, neurocognitive functioning, social cognition, and functional outcome are related, the direction of their associations is not clear.

The aim of the study was to analyze the influence of social cognition as a mediator between cognitive reserve and cognitive domains on functioning in FEP both at baseline and at 2 years.

The sample of the study was composed of 282 FEP patients followed up for 2 years. To analyze whether social cognition mediates the influence of cognitive reserve and cognitive domains on functioning, a path analysis was performed. The statistical significance of any mediation effects was evaluated by bootstrap analysis.

At baseline, as neither cognitive reserve nor the cognitive domains studied were related to functioning, the conditions for mediation were not satisfied. Nevertheless, at 2 years of follow-up, social cognition acted as a mediator between cognitive reserve and functioning. Likewise, social cognition was a mediator between verbal memory and functional outcome. The results of the bootstrap analysis confirmed these significant mediations (95% bootstrapped CI (−10.215 to −0.337) and (−4.731 to −0.605) respectively).

Cognitive reserve and neurocognition are related to functioning, and social cognition mediates in this relationship.

This work was supported by the Carlos III Institute of Health and European Fund for Regional Development (PI08/1213, PI11/ 01977, PI14/01900, PI08/01026, PI11/02831, PI14/01621, PI08/1161, PI16/ 00359, PI16/01164, PI18/00805), the Basque Foundation for He

A cumulative environmental exposure score for schizophrenia (exposome score for schizophrenia [ES-SCZ]) may provide potential utility for risk stratification and outcome prediction. Here, we investigated whether ES-SCZ was associated with functioning in patients with schizophrenia spectrum disorder, unaffected siblings, and healthy controls.

This cross-sectional sample consisted of 1,261 patients, 1,282 unaffected siblings, and 1,525 healthy controls. The Global Assessment of Functioning (GAF) scale was used to assess functioning. ES-SCZ was calculated based on our previously validated method. The association between ES-SCZ and the GAF dimensions (symptom and disability) was analyzed by applying regression models in each group (patients, siblings, and controls). Additional models included polygenic risk score for schizophrenia (PRS-SCZ) as a covariate.

ES-SCZ was associated with the GAF dimensions in patients (symptom: B = −1.53, p-value = 0.001; disability: B = −1.44, p-value = 0.001), siblings (symptom: B = −3.07, p-value < 0.001; disability: B = −2.52, p-value < 0.001), and healthy controls (symptom: B = −1.50, p-value < 0.001; disability: B = −1.31, p-value < 0.001). The results remained the same after adjusting for PRS-SCZ. The degree of associations of ES-SCZ with both symptom and disability dimensions were higher in unaffected siblings than in patients and controls. By analyzing an independent dataset (the Genetic Risk and Outcome of Psychosis study), we replicated the results observed in the patient group.

Our findings suggest that ES-SCZ shows promise for enhancing risk prediction and stratification in research practice. From a clinical perspective, ES-SCZ may aid in efforts of clinical characterization, operationalizing transdiagnostic clinical staging models, and personalizing clinical management.

The top biomedical research institutions have traditionally been assumed to provide better medical treatment for their patients. However, this may not necessarily be the case. Low-to-moderate negative associations between research activity and the quality-of-care provided by clinical departments have been described. We aimed to examine this relationship in the psychiatric units of the largest hospitals in Spain.

Scientific publications for 50 hospitals were retrieved from the Web of Science (2006–2015), and quality of mental healthcare data were gathered from Spanish National Health System records (2008–2014). Spearman-rank correlation analyses (adjusting for number of beds and population) were used to examine the associations between research data and quality-of-care outcomes in psychiatry. Stepwise regression models were built in order to determine the predictive value of research productivity for healthcare outcomes.

We found a positive association between research activity indicators (i.e., number of publications, number of citations, cumulative impact factor, and institutional H-index) and better quality-of-care outcomes in psychiatry (i.e., number of readmissions, transfers, and discharges from hospital). In particular, a higher research activity predicted a lower level of readmissions for individuals with psychoses (p = 0.025; R = 0.317), explaining 8.2% of the variance when other factors were accounted for.

Higher research activity is associated with better quality of mental healthcare in psychiatry. Our results can inform decision-making in clinical and research management settings in order to determine the most appropriate quality measures of the impact of research on the prognosis of individuals with psychiatric conditions.

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.

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.

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%).

Pervasive experiences of discrimination are associated with slightly increased odds of psychotic disorders and may minimally help explain excess risk for minority ethnic groups.

Psychosis spectrum disorder has a complex pathoetiology characterised by interacting environmental and genetic vulnerabilities. The present study aims to investigate the role of gene–environment interaction using aggregate scores of genetic (polygenic risk score for schizophrenia (PRS-SCZ)) and environment liability for schizophrenia (exposome score for schizophrenia (ES-SCZ)) across the psychosis continuum.

The sample consisted of 1699 patients, 1753 unaffected siblings, and 1542 healthy comparison participants. The Structured Interview for Schizotypy-Revised (SIS-R) was administered to analyse scores of total, positive, and negative schizotypy in siblings and healthy comparison participants. The PRS-SCZ was trained using the Psychiatric Genomics Consortiums results and the ES-SCZ was calculated guided by the approach validated in a previous report in the current data set. Regression models were applied to test the independent and joint effects of PRS-SCZ and ES-SCZ (adjusted for age, sex, and ancestry using 10 principal components).

Both genetic and environmental vulnerability were associated with case-control status. Furthermore, there was evidence for additive interaction between binary modes of PRS-SCZ and ES-SCZ (above 75% of the control distribution) increasing the odds for schizophrenia spectrum diagnosis (relative excess risk due to interaction = 6.79, [95% confidential interval (CI) 3.32, 10.26], p < 0.001). Sensitivity analyses using continuous PRS-SCZ and ES-SCZ confirmed gene–environment interaction (relative excess risk due to interaction = 1.80 [95% CI 1.01, 3.32], p = 0.004). In siblings and healthy comparison participants, PRS-SCZ and ES-SCZ were associated with all SIS-R dimensions and evidence was found for an interaction between PRS-SCZ and ES-SCZ on the total (B = 0.006 [95% CI 0.003, 0.009], p < 0.001), positive (B = 0.006 [95% CI, 0.002, 0.009], p = 0.002), and negative (B = 0.006, [95% CI 0.004, 0.009], p < 0.001) schizotypy dimensions.

The interplay between exposome load and schizophrenia genetic liability contributing to psychosis across the spectrum of expression provide further empirical support to the notion of aetiological continuity underlying an extended psychosis phenotype.