0000000000136720
AUTHOR
Pak C. Sham
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…
Population differences in the International Multi-Centre ADHD Gene Project.
Contains fulltext : 71443.pdf (Publisher’s version ) (Closed access) The International Multi-Centre ADHD Gene sample consists of 674 families from eight countries (Belgium, England, Germany, Holland, Ireland, Israel, Spain, and Switzerland) ascertained from clinics for combined-type attention definity hyperactivity disorder in an offspring. 863 SNPs were successfully genotyped across 47 autosomal genes implicated in psychiatric disorders yielding a single nucleotide polymorphism (SNP) density of approximately one SNP per 2.5 kb. A global test of heterogeneity showed 269 SNPs nominally significant (expected 43). Inclusion of the Israeli population accounted for approximately 70% of these nom…
DSM-IV Combined Type ADHD Shows Familial Association With Sibling Trait Scores
Contains fulltext : 69060.pdf (Publisher’s version ) (Closed access) Attention deficit hyperactivity disorder (ADHD) is a discrete clinical syndrome characterized by the triad of inattention, hyperactivity, and impulsivity in the context of marked impairments. Molecular genetic studies have been successful in identifying genetic variants associated with ADHD, particularly with DSM-IV inattentive and combined subtypes. Quantitative trait locus (QTL) approaches to linkage and association mapping have yet to be widely used in ADHD research, although twin studies investigating individual differences suggest that genetic liability for ADHD is continuously distributed throughout the population, u…
O4.8. CAN YOU SPOT EMOTIONS? FACIAL EMOTION RECOGNITION AND GENETIC RISK FOR PSYCHOSIS
Background Facial emotion recognition (FER) is a key component of social cognition which has been found consistently impaired in schizophrenia. Deficits in global facial affect recognition have been also found in First Episode Psychosis (FEP) with the same severity as at further stages, especially for anger recognition. Literature to date has shown intermediate emotion recognition ability in either people with family history for psychotic disorders and unaffected relatives of psychotic patients, in a continuum between patients and healthy controls. Furthermore, Polygenic Risk Score (PRS) for schizophrenia has been found associated with social cognition, especially with facial emotion identi…
Longitudinal heritability of childhood aggression
The genetic and environmental contributions to the variation and longitudinal stability in childhood aggressive behavior were assessed in two large twin cohorts, the Netherlands Twin Register (NTR), and the Twins Early Development Study (TEDS; United Kingdom). In NTR, maternal ratings on aggression from the Child Behavior Checklist (CBCL) were available for 10,765 twin pairs at age 7, for 8,557 twin pairs at age 9/10, and for 7,176 twin pairs at age 12. In TEDS, parental ratings of conduct disorder from the Strength and Difficulty Questionnaire (SDQ) were available for 6,897 twin pairs at age 7, for 3,028 twin pairs at age 9 and for 5,716 twin pairs at age 12. In both studies, stability and…
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…
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.
S77. JUMPING TO CONCLUSIONS AND FACIAL EMOTION RECOGNITION IMPAIRMENT IN FIRST EPISODE PSYCHOSIS ACROSS EUROPE
Abstract Background Jumping to conclusions (JTC) is a well-established reasoning and data gathering bias found in patients with psychosis even at illness onset (First Episode Psychosis, FEP). Preliminary work in this field focused primarily on the association with delusions, although jumping to conclusions has also been found in non-deluded schizophrenia patients after remission, and in individual with at risk mental state. Moreover, psychotic patients tend to show impairments in social cognition, struggling in identifying, processing and interpreting social clues. Deficits in facial emotion recognition (FER) – a key component of the construct – represent a well-replicated finding in schizo…
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…
T42. JUMPING TO CONCLUSIONS IS ASSOCIATED WITH THE POLYGENIC RISK SCORE FOR INTELLIGENCE BUT NOT FOR SCHIZOPHRENIA. PRELIMINARY FINDINGS FROM THE EU-GEI STUDY
Background Psychotic patients tend to require less evidence to make decisions compared to general population. This bias named Jumping to Conclusions (JTC) has been found at First Episode Psychosis (FEP) in schizophrenia patients and associated with proneness to psychotic-like experiences in the general population. Interesting findings showed also strong association with lower cognitive functioning in psychotic patients, which in turn has been shown as a candidate intermediate phenotype for psychosis. Overall, findings to date could suggest a shared genetic liability between the occurrence of JTC and psychosis, potentially via IQ. The present study aims to investigate whether the presence of…
Jumping To Conclusions, General Intelligence, And Psychosis Liability: Findings From The Multi-Centre EU-GEI Case-Control Study
AbstractBackgroundThe “jumping to conclusions” (JTC) bias is associated with both psychosis and general cognition but their relationship is unclear. In this study, we set out to clarify the relationship between the JTC bias, IQ, psychosis and polygenic liability to schizophrenia and IQ.Methods817 FEP patients and 1294 population-based controls completed assessments of general intelligence (IQ), and JTC (assessed by the number of beads drawn on the probabilistic reasoning “beads” task) and provided blood or saliva samples from which we extracted DNA and computed polygenic risk scores for IQ and schizophrenia.ResultsThe estimated proportion of the total effect of case/control differences on J…
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…
Linkage studies of bipolar disorder in the region of the Darier's disease gene on chromosome 12q23-24.1.
We have recently described a family in which there is cosegregation of major affective disorder with Darier's disease and have mapped this autosomal dominant skin disorder to 12q23-q24.1. This has provided an interesting candidate region for genetic studies of bipolar disorder. We have studied the segregation of seven markers spanning the Darier's disease locus in 45 bipolar disorder pedigrees and found modest evidence in support of linkage under heterogeneity for 5 of these markers. Nonparametric analyses were suggestive of linkage with a marker at the gene encoding a secretory form of phospholipase A2. Our sample has relatively low power to detect linkage under heterogeneity and independe…
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…
Genetic determinants of heel bone properties: genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium
Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and repli…
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…
Jumping to conclusions, general intelligence, and psychosis liability: Findings from the multi-centre EU-GEI case-control study
This study was funded by the Medical Research Council, the European Community’s Seventh Framework Program grant [agreement HEALTH-F2-2009-241909 (Project EU-GEI)], São Paulo Research Foundation (grant 2012/0417-0), the National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust and King’s College London, the NIHR BRC at University College London and the Wellcome Trust (grant 101272/Z/12/Z).
Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture
Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10 -8). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral…
Linkage to chromosome 1p36 for attention-deficit/hyperactivity disorder traits in school and home settings.
Contains fulltext : 69485.pdf (Publisher’s version ) (Closed access) BACKGROUND: Limited success has been achieved through previous attention-deficit/hyperactivity disorder (ADHD) linkage scans, which were all designed to map genes underlying the dichotomous phenotype. The International Multi-centre ADHD Genetics (IMAGE) project performed a whole genome linkage scan specifically designed to map ADHD quantitative trait loci (QTL). METHODS: A set of 1094 single selected Caucasian ADHD nuclear families was genotyped on a highly accurate and informative single nucleotide polymorphism (SNP) panel. Two quantitative traits measuring the children's symptoms in home and school settings were collecte…
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…
T52. COGNITION, METACOGNITION AND SOCIAL COGNITION AFTER A FIRST EPISODE PSYCHOSIS. PRELIMINARY RESULTS FROM A 5-YEAR-FOLLOW-UP STUDY
Abstract Background Cognitive impairment is considered a core feature of psychotic disorders. Deficits in cognition, metacognition and social cognition have been reported to be correlated, and indeed predictors, of functional outcome or level of disability. Psychotic patients tend to present lower IQ and show impairment in specific cognitive domains, and in social cognition, than controls. Several studies have found deficits in facial emotion recognition (FER) and a higher prevalence of the jumping to conclusions (JTC) reasoning and data gathering biases among psychotic patients, even at time of illness onset, compared to controls. However, the trajectory of this impairment remains unclear.…
The contribution of cannabis use to variation in the incidence of psychotic disorder across Europe (EU-GEI): a multicentre case-control study.
Background: Cannabis use is associated with increased risk of later psychotic disorder but whether it affects incidence of the disorder remains unclear. We aimed to identify patterns of cannabis use with the strongest effect on odds of psychotic disorder across Europe and explore whether differences in such patterns contribute to variations in the incidence rates of psychotic disorder. Methods: We included patients aged 18–64 years who presented to psychiatric services in 11 sites across Europe and Brazil with first-episode psychosis and recruited controls representative of the local populations. We applied adjusted logistic regression models to the data to estimate which patterns of canna…
Identifying gene-environment interactions in schizophrenia: contemporary challenges for integrated, large-scale investigations
European Community Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular genetic variants is small. There are now also a limited number of studies that have investigated molecular genetic candidate gene-environment interactions (G x E), however, so far, thorough replication of findings is rare and G x E research still faces several conceptual and methodological challenges. in this article, we aim to review these recent developments and illustrate h…
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-…