Previous studies identified clusters of first-episode psychosis (FEP) patients based on cognition and premorbid adjustment. This study examined a range of socio-environmental risk factors associated with clusters of FEP, aiming a) to compare clusters of FEP and community controls using the Maudsley Environmental Risk Score for psychosis (ERS), a weighted sum of the following risks: paternal age, childhood adversities, cannabis use, and ethnic minority membership; b) to explore the putative differences in specific environmental risk factors in distinguishing within patient clusters and from controls.

A univariable general linear model (GLS) compared the ERS between 1,263 community controls and clusters derived from 802 FEP patients, namely, low (n = 223) and high-cognitive-functioning (n = 205), intermediate (n = 224) and deteriorating (n = 150), from the EU-GEI study. A multivariable GLS compared clusters and controls by different exposures included in the ERS.

The ERS was higher in all clusters compared to controls, mostly in the deteriorating (β=2.8, 95% CI 2.3 3.4, η2 = 0.049) and the low-cognitive-functioning cluster (β=2.4, 95% CI 1.9 2.8, η2 = 0.049) and distinguished them from the cluster with high-cognitive-functioning. The deteriorating cluster had higher cannabis exposure (meandifference = 0.48, 95% CI 0.49 0.91) than the intermediate having identical IQ, and more people from an ethnic minority (meandifference = 0.77, 95% CI 0.24 1.29) compared to the high-cognitive-functioning cluster.

High exposure to environmental risk factors might result in cognitive impairment and lower-than-expected functioning in individuals at the onset of psychosis. Some patients’ trajectories involved risk factors that could be modified by tailored interventions.

Both childhood adversity (CA) and first-episode psychosis (FEP) have been linked to alterations in cortical thickness (CT). The interactive effects between different types of CAs and FEP on CT remain understudied.

One-hundred sixteen individuals with FEP (mean age = 23.8 ± 6.9 years, 34% females, 80.2% non-affective FEP) and 98 healthy controls (HCs) (mean age = 24.4 ± 6.2 years, 43% females) reported the presence/absence of CA <17 years using an adapted version of the Childhood Experience of Care and Abuse (CECA.Q) and the Retrospective Bullying Questionnaire (RBQ) and underwent magnetic resonance imaging (MRI) scans. Correlation analyses were used to assess associations between brain maps of CA and FEP effects. General linear models (GLMs) were performed to assess the interaction effects of CA and FEP on CT.

Eighty-three individuals with FEP and 83 HCs reported exposure to at least one CA. CT alterations in FEP were similar to those found in participants exposed to separation from parents, bullying, parental discord, household poverty, and sexual abuse (r = 0.50 to 0.25). Exposure to neglect (β = −0.24, 95% CI [−0.37 to −0.12], p = 0.016) and overall maltreatment (β = −0.13, 95% CI [−0.20 to −0.06], p = 0.043) were associated with cortical thinning in the right medial orbitofrontal region.

Cortical alterations in individuals with FEP are similar to those observed in the context of socio-environmental adversity. Neglect and maltreatment may contribute to CT reductions in FEP. Our findings provide new insights into the specific neurobiological effects of CA in early psychosis.

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.

Considering the recently growing number of potentially traumatic events in Europe, the European Psychiatric Association undertook a study to investigate clinicians’ treatment choices for post-traumatic stress disorder (PTSD).

The case-based analysis included 611 participants, who correctly classified the vignette as a case of PTSD, from Central/ Eastern Europe (CEE) (n = 279), Southern Europe (SE) (n = 92), Northern Europe (NE) (n = 92), and Western Europe (WE) (N = 148).

About 82% woulduse antidepressants (sertraline being the most preferred one). Benzodiazepines and antipsychotics were significantly more frequently recommended by participants from CEE (33 and 4%, respectively), compared to participants from NE (11 and 0%) and SE (9% and 3%). About 52% of clinicians recommended trauma-focused cognitive behavior therapy and 35% psychoeducation, irrespective of their origin. In the latent class analysis, we identified four distinct “profiles” of clinicians. In Class 1 (N = 367), psychiatrists would less often recommend any antidepressants. In Class 2 (N = 51), clinicians would recommend trazodone and prolonged exposure therapy. In Class 3 (N = 65), they propose mirtazapine and eye movement desensitization reprocessing therapy. In Class 4 (N = 128), clinicians propose different types of medications and cognitive processing therapy. About 50.1% of participants in each region stated they do not adhere to recognized treatment guidelines.

Clinicians’ decisions for PTSD are broadly similar among European psychiatrists, but regional differences suggest the need for more dialogue and education to harmonize practice across Europe and promote the use of guidelines.

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.

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.

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.

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.

Many autistic children experience difficulties in their communication and language skills development, with consequences for social development into adulthood, often resulting in challenges over the life-course and high economic impacts for individuals, families, and society. The Preschool Autism Communication Trial (PACT) intervention is effective in terms of improved social communication and some secondary outcomes. A previously published within-trial economic analysis found that results at 13 months did not support its cost-effectiveness. We modeled cost-effectiveness over 6 years and across four European countries.

Using simulation modeling, we built on economic analyses in the original trial, exploring longer-term cost-effectiveness at 6 years (in England). We adapted our model to undertake an economic analysis of PACT in Ireland, Italy, and Spain. Data on resource use were taken from the original trial and a more recent Irish observational study.

PACT is cost-saving over time from a societal perspective, even though we confirmed that, at 13 months post-delivery, PACT is more expensive than usual treatment (across all countries) when given to preschool autistic children. After 6 years, we found that PACT has lower costs than usual treatment in terms of unpaid care provided by parents (in all countries). Also, if we consider only out-of-pocket expenses from an Irish study, PACT costs less than usual treatment.

PACT may be recommended as a cost-saving early intervention for families with an autistic child.

Autism is a lifelong complex neurodevelopmental condition that affects brain development and behaviour with significant consequences for everyday life. Despite its personal, familial, and societal impact, Europe-wide harmonised guidelines are still lacking for early detection, diagnosis, and intervention, leading to an overall unsatisfactory autistic person and carer journey.

The care pathway for autistic children and adolescents was analysed in Italy, Spain and the UK from the perspective of carers (using a survey aimed at caregivers of autistic children 0–18 years old), the autistic community, and professionals in order to identify major barriers (treatment gaps) preventing carers from receiving information, support, and timely screening/diagnosis and intervention.

Across all three countries, analysis of the current care pathway showed: long waits from the time carers raised their first concerns about a child’s development and/or behaviour until screening and confirmed diagnosis; delayed or no access to intervention once a diagnosis was confirmed; limited information about autism and how to access early detection services; and deficient support for families throughout the journey.

These findings call for policy harmonisation in Europe to shorten long wait times for diagnosis and intervention and therefore, improve autistic people and their families’ journey experience and quality of life.

Autism and epilepsy often occur together. Epilepsy and other associated conditions have a substantial impact on the well-being of autistic people and their families, reduce quality of life, and increase premature mortality. Despite this, there is a lack of studies investigating the care pathway of autistic children with co-occurring epilepsy in Europe.

We analyzed the care pathway for autistic children with associated epilepsy in Italy, Spain, and the United Kingdom from the perspective of caregivers (using a survey aimed at caregivers of autistic children 0–18 years old), the autistic community, and professionals, in order to identify major barriers preventing caregivers and autistic children from receiving timely screening and treatment of possible co-occurring epilepsy.

Across all three countries, an analysis of the current care pathway showed a lack of systematic screening of epilepsy in all autistic children, lack of treatment of co-occurring epilepsy, and inappropriate use of antiepileptic drugs. A major challenge is the lack of evidence-based harmonized guidelines for autism with co-occurring epilepsy in these countries.

Our findings show both heterogeneity and major gaps in the care pathway for autism with associated epilepsy and the great efforts that caregivers must make for timely screening, diagnosis, and adequate management of epilepsy in autistic children. We call for policy harmonization in Europe in order to improve the experiences and quality of life of autistic people and their families.

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.

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 3 indicators of social disadvantage for each phase: pre-migration, migration, and post-migration.

249 cases and 219 controls were assessed. Pre-migration (OR 1.61, 95%CI 1.06-2.44, p=0.027) and postmigration 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. We found a dose-response effect between number of adversities across all phases and odds of psychosis (≥6: OR 14.09, 95%CI 2.06-96-47, p=0.007).

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 be reduce the excess of psychosis in migrants.

None Declared

Early-onset psychosis (EOP) refers to the development of a first episode of psychosis before 18 years of age. Individuals at clinical high risk for psychosis (CHR-P) include adolescents and young adults, although most evidence has focused on adults. Negative symptoms are important prognostic indicators in psychosis. However, research focusing on children and adolescents is limited.

To provide meta-analytical evidence and a comprehensive review of the status and advances in the diagnosis, prognosis and treatment of negative symptoms in children and adolescents with EOP and at CHR-P.

PRISMA/MOOSE-compliant systematic review (PROSPERO: CRD42022360925) from inception to 18 August 2022, in any language, to identify individual studies conducted in EOP/CHR-P children and adolescents (mean age <18 years) providing findings on negative symptoms. Findings were systematically appraised. Random-effects meta-analyses were performed on the prevalence of negative symptoms, carrying out sensitivity analyses, heterogeneity analyses, publication bias assessment and quality assessment using the Newcastle–Ottawa Scale.

Of 3289 articles, 133 were included (n = 6776 EOP, mean age 15.3 years (s.d. = 1.6), males = 56.1%; n = 2138 CHR-P, mean age 16.1 years (s.d. = 1.0), males = 48.6%). There were negative symptoms in 60.8% (95% CI 46.4%–75.2%) of the children and adolescents with EOP and 79.6% (95% CI 66.3–92.9%) of those at CHR-P. Prevalence and severity of negative symptoms were associated with poor clinical, functional and intervention outcomes in both groups. Different interventions were piloted, with variable results requiring further replication.

Negative symptoms are common in children and adolescents at early stages of psychosis, particularly in those at CHR-P, and are associated with poor outcomes. Future intervention research is required so that evidence-based treatments will become available.

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’.

Functional recovery is a treatment goal that goes beyond symptomatic remission and encompasses multiple aspects of schizophrenia patients’ lives, including quality of life, physical, and mental functioning. There is evidence that long-acting injectable (LAI) treatments promote adherence and reduce rehospitalisation and functional decline, which could facilitate patients’ ability to reach functional recovery. Despite this, LAIs are underused in the first-episode (FEP) and early-phase (EP) patient population, due to physician hesitancy and concerns around stigma. A Delphi panel was held to gain expert consensus on an approach to the domains and assessment of functional recovery elements in FEP and EP schizophrenia patients.

A literature review and input from a steering committee of 5 experts in psychiatry informed statements development for a three-round modified Delphi process. Round one was conducted via one-to-one video conference interviews, and the successive rounds were conducted via electronic surveys, which enabled international collaboration. Statements on the different domains and assessment for functional recovery were presented to 17 psychiatrists, practicing in 7 countries (France, Italy, US, Germany, Spain, Denmark, and UK), experienced in the treatment of schizophrenia with LAIs. Several analysis rules determined whether a statement could progress to the next round and specified the level of agreement required to achieve consensus. Measures of central tendency (mode, mean) and variability (interquartile range) were reported back to help panelists look at their previous responses in the context of the overall group.

A consensus was reached (defined a priori as ≥80% agreement) on all 27 statements covering the dimensions, assessment, and level of achieved functional recovery for FEP and EP patients. The following domains are important to consider when assessing functional recovery: depression, aggressive behaviour, social interaction, family functioning, education/employment, sexual functioning, and leisure activities. Additionally, panellists reached consensus that dimensions should be minimally impairing, if present (excluding sexual functioning) and asked about at every encounter with the patient (excluding sexual functioning and leisure activities). In summary, this Delphi panel yielded agreement that functional recovery is multidimensional and should be assessed regularly as part of usual care on an individual patient level in FEP and EP schizophrenia patients.

Lundbeck Otsuka Alliance

Schizophrenia is among the top ten causes of years lost due to disability. Goals of treatment are evolving beyond remission of psychotic symptoms to include physical and mental functioning, quality of life, and long-term functional recovery. Evidence has shown long-acting injectables (LAIs) are beneficial for schizophrenia patients by increasing treatment adherence and decreasing relapse and rehospitalisation. This potentially reduces disease progression and facilitates functional recovery. However, LAIs are underused and often seen as a last resort for first-episode (FEP) and early-phase (EP) patients, due to physicians’ lack of familiarity and stigma.

A three-round modified Delphi panel was held to gain expert consensus on an approach to functional recovery in FEP and EP patients with LAIs. A literature review and input from a steering committee of 5 experts in psychiatry informed the development of statements. Round one was carried out via one-to-one video conference interviews, and the subsequent rounds were conducted via electronic surveys, which enabled international collaboration. Delphi panellists were 17 psychiatrists with schizophrenia treatment experience, practicing in 7 countries (France, Italy, US, Germany, Spain, Denmark, and UK). Several analysis rules determined whether a statement could progress to the next round and specified the level of agreement required to achieve consensus. Measures of central tendencies (mode, mean) and variability (interquartile range) of aggregated responses from the previous round were reported to panelists to understand their response in relation to the group.

There was consensus (defined a priori as ≥80% agreement) on the 8 statements relating to long-term treatment goals and LAI links to functional recovery. LAI treatment in FEP and EP patients increases adherence and reduces treatment burden and functional decline compared to the same and other oral medication. Additionally, there was consensus that LAIs lead to better treatment outcome and functional recovery. Other important factors to achieving functional recovery include patient attitude towards treatment and psychoeducation. Furthermore, consensus was reached that functional recovery and quality of life are linked. In summary, this Delphi panel yielded agreement that functional recovery is a reachable goal for FEP and EP patients and can be enhanced using LAIs.

Lundbeck Otsuka Alliance

Subjective response (SR) to antipsychotic medication is relevant for quality of life, adherence and recovery. Here, we evaluate (1) the extent of variation in SR in patients using a single antipsychotic; (2) the association between subjective and symptomatic response; and (3) predictors of SR.

Open-label, single treatment condition with amisulpride in 339 patients with a first episode of a schizophrenia spectrum disorder, at most minimally treated before inclusion. Patients were evaluated at baseline, before start with amisulpride and after four weeks of treatment with the Subjective Wellbeing under Neuroleptic scale, the Positive and Negative Syndrome Scale, and the Calgary Depression Scale for Schizophrenia.

(1) 26.8% of the patients had a substantial favorable SR, and 12.4% of the patients experienced a substantial dysphoric SR during treatment with amisulpride. (2) Modest positive associations were found between SR and 4 weeks change on symptom subscales (r = 0.268–0.390, p values < 0.001). (3) Baseline affective symptoms contributed to the prediction of subjective remission, demographic characteristics did not. Lower start dosage of amisulpride was associated with a more favorable SR (r = −0.215, p < 0.001).

We conclude that variation in individual proneness for an unfavorable SR is substantial and only modestly associated with symptomatic response. We need earlier identification of those most at risk for unfavorable SR and research into interventions to improve SR to antipsychotic medication in those at risk.

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.

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.

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.

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.

While shared clinical decision-making (SDM) is the preferred approach to decision-making in mental health care, its implementation in everyday clinical practice is still insufficient. The European Psychiatric Association undertook a study aiming to gather data on the clinical decision-making style preferences of psychiatrists working in Europe.

We conducted a cross-sectional online survey involving a sample of 751 psychiatrists and psychiatry specialist trainees from 38 European countries in 2021, using the Clinical Decision-Making Style – Staff questionnaire and a set of questions regarding clinicians’ expertise, training, and practice.

SDM was the preferred decision-making style across all European regions ([central and eastern Europe, CEE], northern and western Europe [NWE], and southern Europe [SE]), with an average of 73% of clinical decisions being rated as SDM. However, we found significant differences in non-SDM decision-making styles: participants working in NWE countries more often prefer shared and active decision-making styles rather than passive styles when compared to other European regions, especially to the CEE. Additionally, psychiatry specialist trainees (compared to psychiatrists), those working mainly with outpatients (compared to those working mainly with inpatients) and those working in community mental health services/public services (compared to mixed and private settings) have a significantly lower preference for passive decision-making style.

The preferences for SDM styles among European psychiatrists are generally similar. However, the identified differences in the preferences for non-SDM styles across the regions call for more dialogue and educational efforts to harmonize practice across Europe.