Modelling gene-environment interaction in first episodes of psychosis.
Recent research demonstrates the heterogeneous etiology of psychotic disorders, where gen-environment (GxE) interaction plays a key role. Large genetic studies have linked many genetic variants with schizophrenia, but each variant is only associated with a small effect and the GxE interaction contribution has not been evaluated.



The PEPs Project was designed to carefully collect a large amount of genetic and environmental exposure data of 335 FEP patients and 253 matched healthy controls.780single-nucleotide polymorphisms (from 159 candidate genes)and 16 environmental variables previously reported as the main psychosis non-genetic risk factors were analyzed together using entropy-based measures of information gain.



Our analyses identified an interaction between nine SNPs and the exposition to the environmental risk factors of psychosis, showing a clear enrichment of genes linked to serotonin neurotransmission and neurodevelopmental processes.



This study has allowed the identification of several GxE-environment interactions involved in the risk of presenting a FEP. Our results highlight the importance of serotonin neurotransmission interacting with certain environmental stimuli. The serotoninergic system may be playing a key role in the regulatory network of stress and other systems implicated in the emergence and development of psychotic disorders.
Barcelona Clínic SchizophreniaUnit, Hospital Clínic de Barcelona, CIBERSAM, Spain; Universitat de Barcelona, IDIBAPS, Barcelona, Spain. Electronic address: bernardo@clinic.ub.es.
Miguel
M
Bernardo
Barcelona Clínic SchizophreniaUnit, Hospital Clínic de Barcelona, CIBERSAM, Spain.
Miquel
M
Bioque
Barcelona Clínic SchizophreniaUnit, Hospital Clínic de Barcelona, CIBERSAM, Spain.
Bibiana
B
Cabrera
Instituto de Investigación Sanitaria Aragón (IIS Aragón), University of Zaragoza, Spain.
Antonio
A
Lobo
Department of Psychiatry, Hospital Universitario de Alava, CIBERSAM, University of the Basque Country, Spain.
Ana
A
González-Pinto
Child and Adolescent Psychiatry Department, Hospital General Universitario Gregorio Marañón, IiSGM, CIBERSAM, School of Medicine, Universidad Complutense, Madrid, Spain.
Laura
L
Pina
Department of Psychiatry, Hospital de Sant Pau, CIBERSAM, Barcelona, Spain.
Iluminada
I
Corripio
Clinic Hospital Valencia, INCLIVA, CIBERSAM, Valencia University, Spain.
Julio
J
Sanjuán
Department of Psychiatry, Hospital del Mar, Barcelona, IMIM, Barcelona, Spain.
Anna
A
Mané
Department of Child and Adolescent Psychiatry and Psychology, SGR-489, Neurosciences Institute, Hospital Clínic of Barcelona, IDIBAPS, CIBERSAM, University of Barcelona, Spain.
Josefina
J
Castro-Fornieles
Hospital Clínic de Barcelona, Universitat de Barcelona, IDIBAPS, CIBERSAM, Spain.
Eduard
E
Vieta
Child and Adolescent Psychiatry Department, Hospital General Universitario Gregorio Marañón, IiSGM, CIBERSAM, School of Medicine, Universidad Complutense, Madrid, Spain.
Celso
C
Arango
Barcelona Clínic SchizophreniaUnit, Hospital Clínic de Barcelona, CIBERSAM, Spain.
Gisela
G
Mezquida
Department of Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Institutd'InvestigacionsBiomèdiques August Pi i Sunyer (IDIBAPS), CIBERSAM, Barcelona, Spain.
Patricia
P
Gassó
Child and Adolescent Psychiatry Department, Hospital General Universitario Gregorio Marañón, IiSGM, CIBERSAM, School of Medicine, Universidad Complutense, Madrid, Spain.
Mara
M
Parellada
Hospital Ramón y Cajal, Universidad de Alcalá, IRYCIS, CIBERSAM, Madrid, Spain.
Jerónimo
J
Saiz-Ruiz
Psychiatric Department, Complejo Hospitalario de Navarra, Pamplona (Spain), Instituto de Investigación Sanitaria de Navarra (IdiSNA), Spain.
Manuel J
MJ
Cuesta
Department of Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Institutd'InvestigacionsBiomèdiques August Pi i Sunyer (IDIBAPS), CIBERSAM, Barcelona, Spain.
Sergi
S
Mas
D000293:Adolescent; D000328:Adult; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008954:Models, Biological; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011618:Psychotic Disorders / Q000235:genetics* / Q000503:physiopathology; D012189:Retrospective Studies; D013030:Spain; D055815:Young Adult
First episodes psychosis; Gene-environment interaction; Predictive model; Schizophrenia