0000000001310657
AUTHOR
Mara Parellada
Transcriptomic metaanalyses of autistic brains reveals shared gene expression and biological pathway abnormalities with cancer
Este es el artículo que se ha publicado de forma definitiva en: https://molecularautism.biomedcentral.com/articles/10.1186/s13229-019-0262-8 En este artículo también participa Joan Climent, Vera Pancaldi, Lourdes Fañanás, Celso Arango, Mara Parellada, Anaïs Baudot, Daniel Vogt, John L. Rubenstein, Alfonso Valencia y Rafael Tabarés-Seisdedos. Background: Epidemiological and clinical evidence points to cancer as a comorbidity in people with autism spectrum disorders (ASD). A significant overlap of genes and biological processes between both diseases has also been reported. Methods: Here, for the first time, we compared the gene expression profiles of ASD frontal cortex tissues and 22 cancer t…
White Noise Speech Illusions: A Trait-Dependent Risk Marker for Psychotic Disorder?
Supported by the European Community’s Seventh Framework Program under grant agreement No. HEALTH-F2-2009-241909 (Project EU-GEI)
The EUropean Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI)
Funder: FP7 Ideas: European Research Council; doi: http://dx.doi.org/10.13039/100011199; Grant(s): HEALTH-F2-2010-241909
Gene-environment interaction as a predictor of early adjustment in first episode psychosis.
Abstract Background This study aims to explore the gene-environment interaction hypothesis applied to pre-symptomatic neurodevelopmental phenotypes of first episode psychosis (FEP), that is, genetic factors might increase vulnerability to the effects of environmental adverse conditions occurring at later stages of development. Methods We constructed a schematic ‘two-hit’ model, with Val/Val homozygosity for the catechol- O -methyltransferase ( COMT ) Val158Met polymorphism as the ‘first hit’ and history of obstetric complications and parental socioeconomic status as ‘second hits’. Early adjustment, measured using the Premorbid Adjustment Scale, was considered the main outcome. The study pop…
The state of psychiatry in Spain
The 1986 General Health Act and the so-called 'psychiatric reform' were key issues in the development of the mental healthcare system (MHCS) in Spain. The World Health Organization Declaration and Action Plan on Mental Health in 2005 gave it a revitalizing impetus and resulted in the first National Health System (NHS) Mental Health Strategy in 2006. A literature search was performed using MEDLINE, Spanish journals, reference lists, national databases, and European and Spanish official documents to describe the current state of the MHCS in Spain. The main results were: (1) existence of great variability among the autonomous communities with respect to mental health resources and provision of…
Migration history and risk of psychosis: results from the multinational EU-GEI study.
The European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) Project was funded by grant agreement Health-F2-2010-241909 (Project EU-GEI) from the European Community’s Seventh Framework programme.
The collaborative outcomes study on health and functioning during infection times in adults (COH-FIT-Adults): Design and methods of an international online survey targeting physical and mental health effects of the COVID-19 pandemic
BACKGROUND: . High-quality comprehensive data on short-/long-term physical/mental health effects of the COVID-19 pandemic are needed. METHODS: . The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) is an international, multi-language (n=30) project involving >230 investigators from 49 countries/territories/regions, endorsed by national/international professional associations. COH-FIT is a multi-wave, on-line anonymous, cross-sectional survey [wave 1: 04/2020 until the end of the pandemic, 12 months waves 2/3 starting 6/24 months threreafter] for adults, adolescents (14-17), and children (6-13), utilizing non-probability/snowball and representative samp…
Auditory hallucinations in first-episode psychosis: A voxel-based morphometry study
Abstract Background Auditory hallucinations (AH) are a core symptom of psychosis. The brain abnormalities responsible for AH remain controversial due to inconsistent and conflicting findings across studies, with substantial confounding factors, such as chronicity. Few studies have examined the pathological changes that occur in the gray matter (GM) of patients with first-episode psychosis (FEP) and AH. The present study aims to validate the presence and characteristics of these structural abnormalities in relation to the intensity of psychotic symptoms and AH in a larger homogeneous sample than those of previous studies. Methods A magnetic resonance voxel-based morphometric analysis was app…
Age at First Episode Modulates Diagnosis-Related Structural Brain Abnormalities in Psychosis.
Brain volume and thickness abnormalities have been reported in first-episode psychosis (FEP). However, it is unclear if and how they are modulated by brain developmental stage (and, therefore, by age at FEP as a proxy). This is a multicenter cross-sectional case-control brain magnetic resonance imaging (MRI) study. Patients with FEP (n = 196), 65.3% males, with a wide age at FEP span (12-35 y), and healthy controls (HC) (n = 157), matched for age, sex, and handedness, were scanned at 6 sites. Gray matter volume and thickness measurements were generated for several brain regions using FreeSurfer software. The nonlinear relationship between age at scan (a proxy for age at FEP in patients) and…
Additional file 1: of Transcriptomic metaanalyses of autistic brains reveals shared gene expression and biological pathway abnormalities with cancer
Table S1. Datasets included in our study. Table S2. Age, gender and pmi distributions between cases and control samples at each step of the preprocessing procedure at the asd defferentail gene expression meta-analysis. Table S3. Final samples included in the asd meta-analysis. Table S4. Jointly same direction derregulated genes in asd ans sddcs and jointly oposite direction derregulated genes in asd and oddcs. Table S5. Genes jointly deregulated in asd and in sddcs and oddcs. Figure S1. Comaprison of differential gene expression analysis using limma with rlog transformed data and two state of the art rnaseq differential expression metdos. Figure S2. Patient overlap in the three asd studies.…
A replication study of JTC bias, genetic liability for psychosis and delusional ideation
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)
Estimating Exposome Score for Schizophrenia Using Predictive Modeling Approach in Two Independent Samples: The Results From the EUGEI Study
The EUGEI project was supported by the grant agreement HEALTH-F2-2010-241909 from the European Community’s Seventh Framework Programme. The authors are grateful to the patients and their families for participating in the project. They also thank all research personnel involved in the GROUP project, in particular J. van Baaren, E. Veermans, G. Driessen, T. Driesen, E. van’t Hag and J. de Nijs. Bart PF Rutten was funded by a VIDI award number 91718336 from the Netherlands Scientific Organisation.
Pre-training inter-rater reliability of clinical instruments in an international psychosis research project.
International audience
Impact of NTRK2, DRD2 and ACE polymorphisms on prolactin levels in antipsychotic-treated patients with first-episode psychosis.
Background: Hyperprolactinemia is a common side-effect of antipsychotics (APs), which may trigger serious secondary problems and compromise the adherence to treatment which is crucial for prognosis, especially in patients presenting with a first-episode of psychosis (FEP). Aims: We evaluated, in some cases for the first time, the effect of polymorphisms in multiple candidate genes on serum prolactin (PRL) levels in an AP-treated FEP cohort recruited in the multicenter PEPs study (Phenotype − genotype and environmental interaction; Application of a predictive model in first psychotic episodes). Methods: PRL concentration was measured in serum from 222 patients. A total of 167 polymorphisms w…
Treated Incidence of Psychotic Disorders in the Multinational EU-GEI Study
Importance: Psychotic disorders contribute significantly to the global disease burden, yet the latest international incidence study of psychotic disorders was conducted in the 1980s. Objectives: To estimate the incidence of psychotic disorders using comparable methods across 17 catchment areas in 6 countries and to examine the variance between catchment areas by putative environmental risk factors. Design, Setting, and Participants: An international multisite incidence study (the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions) was conducted from May 1, 2010, to April 1, 2015, among 2774 individuals from England (2 catchment areas), France (3 catch…
Physical and mental health impact of COVID-19 on children, adolescents, and their families: The Collaborative Outcomes study on Health and Functioning during Infection Times-Children and Adolescents (COH-FIT-C&A)
BACKGROUND: The COVID-19 pandemic has altered daily routines and family functioning, led to closing schools, and dramatically limited social interactions worldwide. Measuring its impact on mental health of vulnerable children and adolescents is crucial. METHODS: The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT - www.coh-fit.com) is an on-line anonymous survey, available in 30 languages, involving >230 investigators from 49 countries supported by national/international professional associations. COH-FIT has thee waves (until the pandemic is declared over by the WHO, and 6-18 months plus 24-36 months after its end). In addition to adults, COH-FIT also…
The EUropean Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI): Incidence and First-Episode Case-Control Programme. Soc Psychiatry Psychiatr Epidemiol
Purpose: The EUropean Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study contains an unparalleled wealth of comprehensive data that allows for testing hypotheses about (1) variations in incidence within and between countries, including by urbanicity and minority ethnic groups; and (2) the role of multiple environmental and genetic risk factors, and their interactions, in the development of psychotic disorders. Methods: Between 2010 and 2015, we identified 2774 incident cases of psychotic disorders during 12.9 million person-years at risk, across 17 sites in 6 countries (UK, The Netherlands, France, Spain, Italy, and Brazil). Of the 2774 incident…
The prevention of relapses in first episodes of schizophrenia: The 2EPs Project, background, rationale and study design.
Up to 80% of first-episode psychosis patients suffer a relapse within five years of the remission. Relapse should be an important focus of prevention given the potential harm to the patient and family. It threatens to disrupt their psychosocial recovery, increases the risk of resistance to treatment and has been associated with greater direct and indirect costs for society. Based on a previous project entitled "Genotype-phenotype and environment. Application to a predictive model in first psychotic episodes" (PEPs Project), the project "Clinical and neurobiological determinants of second episodes of schizophrenia. Longitudinal study of first episode of psychosis" was designed, also known as…
Evidence, and replication thereof, that molecular-genetic and environmental risks for psychosis impact through an affective pathway
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…
Smoking does not impact social and non-social cognition in patients with first episode psychosis.
Abstract Background Many studies having shown significant improvements in non-social and social cognitive performance in smoking FEP patients compared to non-smoking FEP patients. The findings are controversial. This study analyzed the effects of tobacco use on non-social and social cognitive function in a large group of FEP patients and a matched healthy control group. Methods A sample of 335 patients with FEP and 253 healthy controls was divided into four subgroups: control tobacco users (CTU), control non-tobacco users (CNTU), patient tobacco users (PTU) and patient non-tobacco users (PNTU). Demographic variables, tobacco use variables (presence or absence, frequency and duration of toba…
Examining facial emotion recognition as an intermediate phenotype for psychosis: Findings from the EUGEI study
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 (...)
Examining the association between exposome score for schizophrenia and functioning in schizophrenia, siblings, and healthy controls: results from the EUGEI study
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)...
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…
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-…
Unraveling the relationship of loneliness and isolation in schizophrenia: Polygenic dissection and causal inference
ABSTRACTThere is increasing recognition of the association between loneliness and social isolation (LNL-ISO) with schizophrenia. Here, we demonstrate significant LNL-ISO polygenic score prediction on schizophrenia in an independent case-control sample (N=3,488). We then dissect schizophrenia predisposing variation into subsets of variants based on their effect on LNL-ISO. Genetic variation with concordant effects in both phenotypes show significant SNP-based heritability enrichment, higher polygenic predictive ability in females and positive covariance with other mental disorders such as depression, anxiety, attention-deficit hyperactivity, alcohol use disorder, and autism. Conversely, gene…
Additional file 5: of Transcriptomic metaanalyses of autistic brains reveals shared gene expression and biological pathway abnormalities with cancer
Full differential gene expression meta-analysis results of cancer data. (ZIP 31237 kb)
Additional file 3: of Transcriptomic metaanalyses of autistic brains reveals shared gene expression and biological pathway abnormalities with cancer
Full ASD GSEA pre-ranked enrichment results for different molecular signatures (C2, H, GO_BP, GO_CC, and GO_MF). (XLSX 698 kb)
Additional file 5: of Transcriptomic metaanalyses of autistic brains reveals shared gene expression and biological pathway abnormalities with cancer
Full differential gene expression meta-analysis results of cancer data. (ZIP 31237 kb)
Additional file 3: of Transcriptomic metaanalyses of autistic brains reveals shared gene expression and biological pathway abnormalities with cancer
Full ASD GSEA pre-ranked enrichment results for different molecular signatures (C2, H, GO_BP, GO_CC, and GO_MF). (XLSX 698 kb)
Additional file 4: of Transcriptomic metaanalyses of autistic brains reveals shared gene expression and biological pathway abnormalities with cancer
gProfileR biological process overrepresentation results of the genes contained in the significant intersections of ASD, SDDCs, and ODDCs. (XLSX 233 kb)
Additional file 2: of Transcriptomic metaanalyses of autistic brains reveals shared gene expression and biological pathway abnormalities with cancer
Full ASD differential gene expression meta-analysis results. (CSV 1387 kb)
Additional file 2: of Transcriptomic metaanalyses of autistic brains reveals shared gene expression and biological pathway abnormalities with cancer
Full ASD differential gene expression meta-analysis results. (CSV 1387 kb)
Additional file 4: of Transcriptomic metaanalyses of autistic brains reveals shared gene expression and biological pathway abnormalities with cancer
gProfileR biological process overrepresentation results of the genes contained in the significant intersections of ASD, SDDCs, and ODDCs. (XLSX 233 kb)