Pharmacogenetic study of antipsychotic induced acute extrapyramidal symptoms in a first episode psychosis cohort: role of dopamine, serotonin and glutamate candidate genes.
This study investigated whether the risk of presenting antipsychotic (AP)-induced extrapyramidal symptoms (EPS) could be related to single-nucleotide polymorphisms (SNPs) in a naturalistic cohort of first episode psychosis (FEP) patients. Two hundred and two SNPs in 31 candidate genes (involved in dopamine, serotonin and glutamate pathways) were analyzed in the present study. One hundred and thirteen FEP patients (43 presenting EPS and 70 non-presenting EPS) treated with high-potency AP (amisulpride, paliperidone, risperidone and ziprasidone) were included in the analysis. The statistical analysis was adjusted by age, gender, AP dosage, AP combinations and concomitant treatments as covariates. Four SNPs in different genes (DRD2, SLC18A2, HTR2A and GRIK3) contributed significantly to the risk of EPS after correction for multiple testing (P<1 × 10(-4)). These findings support the involvement of dopamine, serotonin and glutamate pathways in AP-induced EPS.
Department of Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Barcelona, Spain.|Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM),Madrid, Spain.
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Mas
Department of Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Barcelona, Spain.|Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM),Madrid, Spain.
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Gassó
Department of Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Barcelona, Spain.|Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM),Madrid, Spain.
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Lafuente
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM),Madrid, Spain.|Barcelona Clínic Schizophrenia Unit, Hospital Clínic de Barcelona, Barcelona, Spain.
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Bioque
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM),Madrid, Spain.|Department of Medicine and Psychiatry, Instituto de Investigación Sanitaria Aragón (IIS Aragón), University of Zaragoza, Zaragoza, Spain.
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Lobo
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM),Madrid, Spain.|Department of Psychiatry, Hospital Universitario de Alava, University of the Basque Country, Leioa, Spain.
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Gonzàlez-Pinto
Department of Psychiatry, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
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Olmeda
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM),Madrid, Spain.|Department of Psychiatry, Hospital de Sant Pau, Barcelona, Spain.
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Corripio
CICAB Clinical Research Centre, Extremadura University Hospital and Medical School Servicio Extremeño de Salud, Badajoz, Spain.
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Llerena
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM),Madrid, Spain.|Barcelona Clínic Schizophrenia Unit, Hospital Clínic de Barcelona, Barcelona, Spain.
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Cabrera
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM),Madrid, Spain.|Hospital Ramon y Cajal, Universidad de Alcala, IRYCIS, Madrid, Spain.
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Saiz-Ruiz
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM),Madrid, Spain.|Barcelona Clínic Schizophrenia Unit, Hospital Clínic de Barcelona, Barcelona, Spain.|Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Barcelona, Spain.
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Bernardo
D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001480:Basal Ganglia Diseases / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D016022:Case-Control Studies; D002648:Child; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D018698:Glutamic Acid / Q000378:metabolism*; D006239:Haplotypes; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D010597:Pharmacogenetics; D000071184:Pharmacogenomic Variants; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011618:Psychotic Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000235:genetics; D018092:Kainic Acid Receptors / Q000235:genetics; D018570:Risk Assessment; D012307:Risk Factors; D012701:Serotonin / Q000378:metabolism*; D013030:Spain; D016896:Treatment Outcome; D050493:Vesicular Monoamine Transport Proteins / Q000235:genetics; D055815:Young Adult; D000097808:GluK3 Kainate Receptor
D014150:Antipsychotic Agents; D004298:Dopamine; D018698:Glutamic Acid; D044402:Receptor, Serotonin, 5-HT2A; D017448:Receptors, Dopamine D2; D018092:Kainic Acid Receptors; D012701:Serotonin; D050493:Vesicular Monoamine Transport Proteins; D000097808:GluK3 Kainate Receptor; C581293:DRD2 protein, human; C493452:SLC18A2 protein, human