title: Gene-environment interaction as a predictor of early adjustment in first episode psychosis.
abstract: 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.
  
  
  
  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 population comprised 221 adolescents and adults with FEP and 191 sex- and age-matched controls.
  
  
  
  The interaction between the Val/Val COMT genotype and a positive history of obstetric complications plus low parental socioeconomic status was significantly associated with poorer early adjustment. These results were observed both in FEP individuals and in controls, and remained significant after controlling for age, sex, and diagnosis.
  
  
  
  Individuals carrying Val/Val seem to be more sensitive to the synergistic effect of environmental factors acting early in neurodevelopment, which leads to vulnerability phenotypes such as impaired early adjustment.
authors.affiliation: Department of Child and Adolescent Psychiatry, Hospital General Universitario Gregorio Marañón, CIBERSAM, IiSGM, School of Medicine, Universidad Complutense, Madrid, Spain. Electronic address: david.fraguas@cibersam.es.
authors.forename: David
authors.initials: D
authors.lastname: Fraguas
authors.affiliation: Department of Child and Adolescent Psychiatry, Hospital General Universitario Gregorio Marañón, CIBERSAM, IiSGM, School of Medicine, Universidad Complutense, Madrid, Spain.
authors.forename: Covadonga M
authors.initials: CM
authors.lastname: Díaz-Caneja
authors.affiliation: Department of Psychiatry, Institut d'Investigació Biomèdica-Sant Pau (IIB-SANT PAU), Hospital de la Santa Creu i Sant Pau, Barcelona; Universitat Autònoma de Barcelona (UAB), CIBERSAM, Barcelona, Spain.
authors.forename: Iluminada
authors.initials: I
authors.lastname: Corripio
authors.affiliation: BIOARABA Health Research Institute. OSI Araba. University Hospital. University of the Basque Country, CIBERSAM, Vitoria, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: González-Pinto
authors.affiliation: Instituto de Investigación Sanitaria de Aragón (IIS Aragón), University of Zaragoza, CIBERSAM, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Lobo
authors.affiliation: Barcelona Clinic Schizophrenia Unit, Neuroscience Institute, Hospital Clinic of Barcelona, CIBERSAM, Spain.
authors.forename: Miquel
authors.initials: M
authors.lastname: Bioque
authors.affiliation: Department of Psychiatry, Complejo Hospitalario de Navarra, IdiSNA, Pamplona, Spain.
authors.forename: Manuel J
authors.initials: MJ
authors.lastname: Cuesta
authors.affiliation: Department of Psychiatry, Hospital Clinic, University of Valencia, INCLIVA, CIBERSAM, Valencia, Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: Sanjuán
authors.affiliation: Department of Child and Adolescent Psychiatry, Hospital General Universitario Gregorio Marañón, CIBERSAM, IiSGM, School of Medicine, Universidad Complutense, Madrid, Spain.
authors.forename: Elisa
authors.initials: E
authors.lastname: Rodríguez-Toscano
authors.affiliation: Departament de Biologia Evolutiva, Ecologia i Ciències Ambientals, Facultat de Biologia, Universitat de Barcelona, IBUB, CIBERSAM, Barcelona, Spain.
authors.forename: Bárbara
authors.initials: B
authors.lastname: Arias
authors.affiliation: FIDMAG Hermanas Hospitalarias, CIBERSAM, Barcelona, Spain.
authors.forename: Salvador
authors.initials: S
authors.lastname: Sarró
authors.affiliation: Barcelona Clínic Schizophrenia Unit, Neuroscience Institute, Hospital Clínic de Barcelona, CIBERSAM, Barcelona, Spain.
authors.forename: Bibiana
authors.initials: B
authors.lastname: Cabrera
authors.affiliation: Institut de Neuropsiquiatria i Addiccions, Hospital del Mar, Barcelona, Spain; IMIM (Hospital del Mar Medical Research Institute), Barcelona; Department of Psychiatry and Forensic Medicine, Autonomous University of Barcelona UAB, Bellaterra, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Bulbena
authors.affiliation: Bipolar Disorder Unit, Institute of Neuroscience, Hospital Clinic, IDIBAPS, CIBERSAM, University of Barcelona, Barcelona, Spain.
authors.forename: Eduard
authors.initials: E
authors.lastname: Vieta
authors.affiliation: Department of Child and Adolescent Psychiatry and Psychology, SGR489, Institute of Neuroscience, Hospital Clínic of Barcelona, IDIBAPS, CIBERSAM, Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Barcelona, Spain.
authors.forename: Josefina
authors.initials: J
authors.lastname: Castro-Fornieles
authors.affiliation: Department of Child and Adolescent Psychiatry, Hospital General Universitario Gregorio Marañón, CIBERSAM, IiSGM, School of Medicine, Universidad Complutense, Madrid, Spain.
authors.forename: Celso
authors.initials: C
authors.lastname: Arango
authors.affiliation: Barcelona Clínic Schizophrenia Unit, Neurosciences Institute, Hospital Clínic, Barcelona, Spain; Department of Medicine, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain.
authors.forename: Miquel
authors.initials: M
authors.lastname: Bernardo
authors.affiliation: Department of Child and Adolescent Psychiatry, Hospital General Universitario Gregorio Marañón, CIBERSAM, IiSGM, School of Medicine, Universidad Complutense, Madrid, Spain.
authors.forename: Mara
authors.initials: M
authors.lastname: Parellada
mesh_terms: D000328:Adult; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008715:Methionine / Q000235:genetics; D010290:Parents / Q000523:psychology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011618:Psychotic Disorders / Q000175:diagnosis* / Q000235:genetics*; D012189:Retrospective Studies; D018709:Statistics, Nonparametric; D014633:Valine / Q000235:genetics; D055815:Young Adult
chemical_list: D008715:Methionine; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase; D014633:Valine
keywords: COMT; Obstetric complications; Parental socioeconomic status; Premorbid adjustment; Schizophrenia