0000000000469107
AUTHOR
Alexander Richards
showing 21 related works from this author
Are Polygenic Risk Scores for Major Mental Disorders Associated with General or Specific Psychosis Symptom dimensions?
2019
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 Relationship Between Polygenic Risk Scores and Cognition in Schizophrenia
2020
Abstract Background Cognitive impairment is a clinically important feature of schizophrenia. Polygenic risk score (PRS) methods have demonstrated genetic overlap between schizophrenia, bipolar disorder (BD), major depressive disorder (MDD), educational attainment (EA), and IQ, but very few studies have examined associations between these PRS and cognitive phenotypes within schizophrenia cases. Methods We combined genetic and cognitive data in 3034 schizophrenia cases from 11 samples using the general intelligence factor g as the primary measure of cognition. We used linear regression to examine the association between cognition and PRS for EA, IQ, schizophrenia, BD, and MDD. The results wer…
Examining the independent and joint effects of genomic and exposomic liabilities for schizophrenia across the psychosis spectrum
2020
The EUGEI project was supported by the European Community’s Seventh Framework Program under grant agreement no. HEALTH-F2-2009-241909 (Project EU-GEI). Dr O’Donovan is supported by MRC programme grant (G08005009) and an MRC Centre grant (MR/ L010305/1). Dr Rutten was funded by a VIDI award number 91718336 from the Netherlands Scientific Organisation. Drs Guloksuz and van Os are supported by the Ophelia research project, ZonMw grant number: 636340001. Dr Arango was supported by the Spanish Ministry of Science and Innovation; Instituto de Salud Carlos III (SAM16PE07CP1, PI16/02012, PI19/024); CIBERSAM; Madrid Regional Government (B2017/BMD-3740, AGES-CM-2); Fundación Familia Alonso and Fundac…
Schizophrenia polygenic risk score and cannabis use modify psychosis expression in first episode psychosis patients and population controls
2019
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…
Duration of untreated psychosis in first-episode psychosis is not associated with common genetic variants for major psychiatric conditions: results f…
2021
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).
A replication study of JTC bias, genetic liability for psychosis and delusional ideation
2022
The EUGEI project was supported by the European Community's Seventh Framework Program under grant agreement No. HEALTH-F2-2009-241909 (Project EU-GEI). Dr O'Donovan is supported by MRC programme grant (G08005009) and an MRC Centre grant (MR/L010305/1)
Jumping To Conclusions, General Intelligence, And Psychosis Liability: Findings From The Multi-Centre EU-GEI Case-Control Study
2019
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
2018
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
2021
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 an…
2019
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
2021
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).
Evidence, and replication thereof, that molecular-genetic and environmental risks for psychosis impact through an affective pathway
2022
AbstractBackgroundThere is evidence that environmental and genetic risk factors for schizophrenia spectrum disorders are transdiagnostic and mediated in part through a generic pathway of affective dysregulation.MethodsWe analysed to what degree the impact of schizophrenia polygenic risk (PRS-SZ) and childhood adversity (CA) on psychosis outcomes was contingent on co-presence of affective dysregulation, defined as significant depressive symptoms, in (i) NEMESIS-2 (n = 6646), a representative general population sample, interviewed four times over nine years and (ii) EUGEI (n = 4068) a sample of patients with schizophrenia spectrum disorder, the siblings of these patients and controls.ResultsT…
Ks0andΛproduction inppinteractions ats=0.9and 7 TeV measured with the ATLAS detector at the LHC
2012
The production of K(S)(0) and Lambda hadrons is studied in pp collision data at root s = 0.9 and 7 TeV collected with the ATLAS detector at the LHC using a minimum-bias trigger. The observed distributions of transverse momentum, rapidity, and multiplicity are corrected to hadron level in a model-independent way within well-defined phase-space regions. The distribution of the production ratio of (Lambda) over bar to Lambda baryons is also measured. The results are compared with various Monte Carlo simulation models. Although most of these models agree with data to within 15% in the K(S)(0) distributions, substantial disagreements are found in the Lambda distributions of transverse momentum.
Examining facial emotion recognition as an intermediate phenotype for psychosis: Findings from the EUGEI study
2022
The EUGEI project was supported by the European Community’s Seventh Framework Program under grant agreement No. HEALTH-F2- 2009-241909 (Project EU-GEI). Dr. Arango was supported by the Spanish Ministry of Science and Innovation; Instituto de Salud Carlos III (SAM16-PE07CP1, PI16/02012, PI19/024); CIBERSAM (...)
Use of multiple polygenic risk scores for distinguishing schizophrenia-spectrum disorder and affective psychosis categories in a first-episode sample…
2022
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…
Measurement of the WW cross section in s=7 TeV pp collisions with the ATLAS detector and limits on anomalous gauge couplings
2012
This Letter reports a measurement of the W W production cross section in root s = 7 TeV pp collisions using data corresponding to an integrated luminosity of 1.02 fb(-1) collected with the ATLAS de ...
Examining the association between exposome score for schizophrenia and functioning in schizophrenia, siblings, and healthy controls: results from the…
2021
European Community's Seventh Framework Program, European Commission [HEALTH-F2-2009-241909]; Scientific and Technological Research Council of Turkey, 2219 International Postdoctoral Research Fellowship Program; Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (SAM16PE07CP1, PI16/02012, and PI19/024)...
Identifying gene-environment interactions in schizophrenia: contemporary challenges for integrated, large-scale investigations
2014
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 PSYC…
2019
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…
Search for an excess of events with an identical flavour lepton pair and significant missing transverse momentum in root s=7 TeV proton-proton collis…
2011
Results are presented of a search for supersymmetric particles decaying into final states with significant missing transverse momentum and exactly two identical flavour leptons (e or mu) of opposite charge in sqrt{s}=7 TeV collisions at the Large Hadron Collider. This channel is particularly sensitive to supersymmetric particle cascade decays producing flavour correlated lepton pairs. Flavour uncorrelated backgrounds are subtracted using a sample of opposite flavour lepton pair events. Observation of an excess beyond Standard Model expectations following this subtraction procedure would offer one of the best routes to measuring the masses of supersymmetric particles. In a data sample corres…
IS THE ERA OF CANDIDATE GENES X CANNABIS USE REALLY DEAD?
2019
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…