The Maudsley Environmental Risk Score for Psychosis

AbstractBackgroundRisk prediction algorithms have long been used in health research and practice (e.g. prediction of cardiovascular disease and diabetes). However, similar tools have not been developed for mental health. For example, for psychotic disorders, attempts to sum environmental risk are rare, unsystematic and dictated by available data. In light of this, we sought to develop a valid, easy to use measure of the aggregate environmental risk score (ERS) for psychotic disorders.MethodsWe reviewed the literature to identify well-replicated and validated environmental risk factors for psychosis that combine a significant effect and large-enough prevalence. Pooled estimates of relative r…

Are Polygenic Risk Scores for Major Mental Disorders Associated with General or Specific Psychosis Symptom dimensions?

Background Psychotic symptoms can be conceptualised as dimensions of psychopathology cutting across diagnostic boundaries. Thus, they might be considered enhanced quantitative phenotypes to relate to genetic variants as summarised by Polygenic Risk Scores (PRSs) for Major Mental Disorders (MMDs), including Schizophrenia (SZ), Bipolar Disorder (BP), and Major Depressive Disorder (MDD). The objectives of this study were to: 1) identify the dimensional structure of symptoms at First Episode Psychosis (FEP), testing whether a bi-factor model statistically fits the conceptualization of psychosis as a single common construct (general psychosis factor) while also recognising multidimensionality (p…

THE RELATION OF THE PSYCHOSIS CONTINUUM WITH SCHIZOPHRENIA POLYGENIC RISK SCORE AND CANNABIS USE

Transdiagnostic dimensions of psychopathology at first episode psychosis: findings from the multinational EU-GEI study.

Background\ud The value of the nosological distinction between non-affective and affective psychosis has frequently been challenged. We aimed to investigate the transdiagnostic dimensional structure and associated characteristics of psychopathology at First Episode Psychosis (FEP). Regardless of diagnostic categories, we expected that positive symptoms occurred more frequently in ethnic minority groups and in more densely populated environments, and that negative symptoms were associated with indices of neurodevelopmental impairment.\ud \ud Method\ud This study included 2182 FEP individuals recruited across six countries, as part of the EUropean network of national schizophrenia networks st…

Synergistic effects of childhood adversity and polygenic risk in first-episode psychosis

The European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) Project is funded by grant agreement HEALTH-F2-2010-241909 (Project EU-GEI) from the European Community’s Seventh Framework Programme.

T110. FIRST EPISODE PSYCHOTIC PATIENTS WITH A HISTORY OF FREQUENT CANNABIS USE EXPRESS MORE POSITIVE SYMPTOMS AT ILLNESS ONSET THAN THOSE WHO NEVER USED CANNABIS

Abstract Background Robust evidence has demonstrated that cannabis use increases the risk to develop psychotic disorders. However, a limited number of studies have investigated if and how cannabis use influences psychopathology profiles at first episode psychosis (FEP). Based on the evidence that dopamine dysfunction contributes to explain positive symptoms in psychosis, and that the main cannabis’ psychoactive component, Δ9-Tetrahydrocannabinol (THC), modulates the dopamine system, we hypothesise that: 1) positive symptoms at FEP are more common among psychotic patients who used cannabis compared with never users; 2) this association is a dose-response relationship. Methods We analyzed a s…

Schizophrenia polygenic risk score and cannabis use modify psychosis expression in first episode psychosis patients and population controls

AbstractBackgroundDiagnostic categories within the psychosis spectrum are widely used in clinical practice, however psychosis may occur on a continuum. Therefore, we explored whether the continuous distribution of psychotic symptoms across categories is a function of genetic as well as environmental risk factors, such as polygenic risk scores (PRSs) and cannabis use.MethodsAs part of the EU-GEI study, we genotyped first episode psychosis patients (FEP) and population controls, for whom transdiagnostic dimensions of psychotic symptoms or experiences were generated using item response bi-factor modelling. Linear regression was used, separately in patients and controls, to test the association…

FIRST EPISODE PSYCHOTIC PATIENTS WITH A HISTORY OF FREQUENT CANNABIS USE EXPRESS MORE POSITIVE SYMPTOMS AT ILLNESS ONSET THAN THOSE WHO NEVER USED CANNABIS

Background: Robust evidence has demonstrated that cannabis use increases the risk to develop psychotic disorders. However, a limited number of studies have investigated if and how cannabis use influences psychopathology profiles at first episode psychosis (FEP). Based on the evidence that dopamine dysfunction contributes to explain positive symptoms in psychosis, and that the main cannabis’ psychoactive component, Δ9-Tetrahydrocannabinol (THC), modulates the dopamine system, we hypothesise that: 1) positive symptoms at FEP are more common among psychotic patients who used cannabis compared with never users; 2) this association is a dose-response relationship. Methods: We analyzed a sample o…

The influence of risk factors on the onset and outcome of psychosis: What we learned from the GAP study

The GAP multidisciplinary study carried out in South London, recruited 410 first episode of psychosis patients and 370 controls; the aim was to elucidate the multiple genetic and environmental factors influencing the onset and outcome of psychosis. The study demonstrated the risk increasing effect of adversity in childhood (especially parental loss, abuse, and bullying) on onset of psychosis especially positive symptoms. Adverse life events more proximal to onset, being from an ethnic minority, and cannabis use also played important roles; indeed, one quarter of new cases of psychosis could be attributed to use of high potency cannabis. The “jumping to conclusions” bias appeared to mediate …

IS THE ERA OF CANDIDATE GENES X CANNABIS USE REALLY DEAD?

Background: Historically, gene X environment examinations in psychotic disorders have employed candidate gene methods and environmental determinants impacting on similar biological mechanisms. However, genome wide association studies (GWAS) show that many variants associated with schizophrenia have a modest effect size on risk. In this respect, it is unclear whether the effect of cannabis on psychosis phenotypes is modified by a few genes, e.g. those involved in dopamine signalling, or by the overall genetic susceptibility to schizophrenia. Indeed, candidate gene approaches might be complementary to GWAS to test gene X cannabis interaction. We aimed to investigate the interactive effects of…

Duration of untreated psychosis in first-episode psychosis is not associated with common genetic variants for major psychiatric conditions: results from the multi-center EU-GEI Study

The EU-GEI Project is funded by the European Community’s Seventh Framework Programme under grant agreement No. HEALTH-F2-2010–241909 (Project EU-GEI).

The relationship of symptom dimensions with premorbid adjustment and cognitive characteristics at first episode psychosis: Findings from the EU-GEI study

Premorbid functioning and cognitive measures may reflect gradients of developmental impairment across diagnostic categories in psychosis. In this study, we sought to examine the associations of current cognition and premorbid adjustment with symptom dimensions in a large first episode psychosis (FEP) sample. We used data from the international EU-GEI study. Bifactor modelling of the Operational Criteria in Studies of Psychotic Illness (OPCRIT) ratings provided general and specific symptom dimension scores. Premorbid Adjustment Scale estimated premorbid social (PSF) and academic adjustment (PAF), and WAIS-brief version measured IQ. A MANCOVA model examined the relationship between symptom di…

5.4 BIOLOGICAL AND EPIDEMIOLOGICAL EXAMINATION OF TRANSDIAGNOSTIC AND SPECIFIC SYMPTOM DIMENSIONS AT PSYCHOSIS ONSET: FINDINGS FROM THE EUGEI STUDY

Abstract Background Current diagnostic models of psychosis have been questioned since Kraepelin’s original dichotomy of dementia praecox and manic depression. Indeed, increasing evidence has suggested that a dimensional approach might be a valid alternative platform for research. However, while an increasing number of studies have investigated how environmental risk factors for affective and non-affective psychosis map onto symptom dimensions, only a few have examined these dimensions in relation to genetic variants as summarised by Polygenic Risk Score (PRS). Furthermore, no studies have examined the putative effect of PRS for Schizophrenia (SZ), Bipolar Disorder (BP), and Major Depressive…

Use of multiple Polygenic Risk Scores for distinguishing Schizophrenia-spectrum disorder and Affective psychosis categories; the EUGEI study

ABSTRACTSchizophrenia (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 EUGEI 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 (573 cases, 1005 controls) of european ancestry from 17 sites as part of the EUGEI study were succes…

The independent and combined influence of schizophrenia polygenic risk score and heavy cannabis use on risk for psychotic disorder: A case-control analysis from the EUGEI study.

Background: Some recent studies have challenged the direction of causality for the association between cannabis use and psychotic disorder, suggesting that cannabis use initiation is explained by common genetic variants associated with risk of schizophrenia. We used data from the European Union Gene-Environment Interaction consortium (EUGEI) case-control study to test for the independent and combined effect of heavy cannabis use, and of Schizophrenia Polygenic risk score (SZ PRS), on risk for psychotic disorder. Methods: Genome-wide data were obtained from 492 first episode psychosis patients (FEPp) and from 787 controls of European Ancestry, and used to generate SZ PRS from the summary res…

S126. THE RELATION OF THE PSYCHOSIS CONTINUUM WITH SCHIZOPHRENIA POLYGENIC RISK SCORE AND CANNABIS USE

Abstract Background There has been much debate about whether research into psychosis should be conducted using symptom dimensions as opposed to diagnostic categories. Indeed, dimensions, like categories, may be practical but arbitrary tools for research and clinical practice; hence, they should not be based on psychometric data only. The aim of this study was to externally validate empirically derived symptom dimensions using combined genetic and environmental data. Specifically, we examined the hypothesis that the continuous multivariate distribution of psychosis is a function of cannabis use and genetic liability to schizophrenia, as summarised by polygenic risk score (SZ-PRS). Methods As…

Cannabis-associated symptom profiles in patients with first episode psychosis and population controls

AbstractObjectiveThe evidence is mixed on whether cannabis use is associated with a particular symptomatology in first episode psychosis (FEP) patients.The authors set out to investigate a) patterns of association between cannabis use and transdiagnostic symptom dimensions; b) whether the extent of use of cannabis contributes to the variation in clinical and subclinical symptom profiles.MethodThe authors analysed data from 901 patients and 1235 controls recruited across six countries, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. Item response modelling was used to estimate two bifactor models, which included genera…

Use of multiple polygenic risk scores for distinguishing schizophrenia-spectrum disorder and affective psychosis categories in a first-episode sample; the EU-GEI study

This work was supported by funding from the European Community’s Seventh Framework Programme under grant agreement No. HEALTH-F2-2010-241909 (Project EU-GEI). (...) CA was supported by the Spanish Ministry of Science and Innovation; Instituto de Salud Carlos III (SAM16PE07CP1, PI16/02012, PI19/024), co-financed by ERDF Funds from the European Commission, ‘A way of making Europe’, CIBERSAM. Madrid Regional Government (B2017/BMD-3740 AGES-CM-2), Fundación Familia Alonso and Fundación Alicia Koplowitz. MB was supported by the Ministry of Economy and Competitivity (PI08/0208; PI11/00325; PI14/00612), Instituto de Salud Carlos III – ERDF Funds from the European Commission, ‘A way of making Europ…

BIOLOGICAL AND EPIDEMIOLOGICAL EXAMINATION OF TRANSDIAGNOSTIC AND SPECIFIC SYMPTOM DIMENSIONS AT PSYCHOSIS ONSET: FINDINGS FROM THE EUGEI STUDY

Background Current diagnostic models of psychosis have been questioned since Kraepelin’s original dichotomy of dementia praecox and manic depression. Indeed, increasing evidence has suggested that a dimensional approach might be a valid alternative platform for research. However, while an increasing number of studies have investigated how environmental risk factors for affective and non-affective psychosis map onto symptom dimensions, only a few have examined these dimensions in relation to genetic variants as summarised by Polygenic Risk Score (PRS). Furthermore, no studies have examined the putative effect of PRS for Schizophrenia (SZ), Bipolar Disorder (BP), and Major Depressive Disorder…

F115POLYGENIC RISK SCORES FOR SCHIZOPHRENIA, BIPOLAR, AND MAJOR DEPRESSIVE DISORDERS PREDICT TRANSDIAGNOSTIC SYMPTOM DIMENSIONS AT FIRST EPISODE PSYCHOSIS

Background: The value of the nosological distinction between non-affective and affective psychosis has consistently been challenged. Indeed, psychotic syndromes are composed of dimensions of psychopathology cutting across diagnostic boundaries. Such transdiagnostic symptom dimensions might be enhanced phenotypes to test for association with common genetic variants for Major Mental Disorders (MMDs) as summarized by Polygenic Risk Scores (PRSs) for Schizophrenia (SZ), Bipolar Disorder (BP), and Major Depressive Disorder (MDD). The objectives of this study were to: 1) identify the symptom dimension structure at First Episode Psychosis (FEP); 2) examine the extent to which MMDs PRSs explain the…

The continuity of effect of schizophrenia polygenic risk score and patterns of cannabis use on transdiagnostic symptom dimensions at first-episode psychosis: findings from the EU-GEI study

The work was supported by Guarantors of Brain post-doctoral clinical fellowship to DQ; Clinician Scientist Medical Research Council fellowship (project reference MR/M008436/1) to MDF; Heisenberg professorship from the German Research Founda- tion (grant no. 389624707) to UR; the National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. The EU-GEI Project is funded by the European Community’s Seventh Framework Programme under grant agreement No. HEALTH-F2-…