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Pharmacogenetic study of antipsychotic induced acute extrapyramidal symptoms in a first episode psychosis cohort: role of dopamine, serotonin and glutamate candidate genes

Abstract

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.

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Acknowledgements

This study was supported by the Ministerio de Economía y Competitividad (Ref. ISCIII 2009-2011: PI 080208)- Instituto de Salud Carlos III-Fondo Europeo de Desarrollo Regional-Unión Europea-Una manera de hacer Europa; the Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM); and by the Government of Catalonia, Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement (2014SGR441). FI-DGR-2013 Contract of the Agència de Gestió d’Ajuts Universitaris i de Recerca, AGAUR (2015 FI_B2 00100) to GM. This work was developed (in part) at the Centro Esther Koplowitz (Barcelona). SNP genotyping services were provided by the Spanish ‘Centro Nacional de Genotipado’ (CEGEN-ISCIII)’ (www.cegen.org).

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AA has received a trainee research staff grant awarded by the University of Barcelona (APIF-UB grants). AB has received grants from the Spanish Ministry of Science and Innovation (FIS). AL has received grants from the Spanish Ministry of Science and Innovation (FIS). AM has received financial support to attend meetings, travel support and served as a speaker from Otsuka and Janssen-Cilag. EV has received grants and served as consultant, advisor or CME speaker for the following entities: AstraZeneca, Bristol-Myers Squibb, Ferrari, Forest Research Institute, Gideon Richter, GlaxoSmithKline, Janssen, Lundbeck, Otsuka, Pfizer, Roche, Snafu-Aventis, Servier, Shire, Sunovion, Takeda, the Brain and Behaviour Foundation, the Spanish Ministry of Science and Innovation (CIBERSAM), the Seventh European Framework Programme (ENBREC) and the Stanley Medical Research Institute. FC has received financial support to attend meetings, travel support and served as advisor or speaker for the following entities: Lilly, Janssen-Cilag, Lundbeck, Otsuka, the Spanish Ministry of Science and Innovation (CIBERSAM) and the Ministry of Science (Carlos III Institute). IB has received grants from CIBERSAM, Fundación Alicia Koplowitz and Institute de Salad Carlos III, and has received honoraria as a speaker for Janssen, as well as support from Otsuka for attending some conferences. MB has been a consultant for, received grant/research support and honoraria from, and been on the speakers/advisory board of ABBiotics, Adamed, Almirall, AMGEN, Eli Lilly, Ferrari, Forum Pharmaceuticals, Gideon, Hersill, Janssen-Cilag, Lundbeck, Otsuka, Pfizer, Roche and Servier, and has obtained research funding from the Spanish Ministry of Health, the Spanish Ministry of Science and Education, the Spanish Ministry of Economy and Competitiveness, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), by the Government of Catalonia, Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and the 7th Framework Program of the European Union. MB has been a consultant for, received grant/research support and honoraria from, and been on the speakers/advisory board of Adamed, Ferrer, Janssen-Cilag, Lundbeck, Otsuka and Pfizer. The remaining authors declare no conflict of interest.

Additional information

PEPs GROUP Gisela Mezquida2,3,4, Ana Meseguer2,3,4, Enrique García Bernardo12, Mara Parellada3,13, Anna Alonso-Solís3,8, Eva Grasa3,8, Miryam Hernandez3,6, Monica Martinez Cengotitabengoa3,6, Fe Barcones3,5, Julio Arbej3,5, Julio Sanjuan3,14, Eduardo J Aguilar3,14, Antonio Balbuena3,15,16, Anna Mané3,15,16, Carla Torrent2,17, Eduard Vieta2,17, Immaculada Baeza2,18, Elena de la Serna2,18, Fernando Contreras3,19,20, Auria Albacete3,19,20, Maria Paz García-Portilla3,21, Julio Bobes3,21, Arantzazu Zabala Rabadán3,22, Rafael Segarra Echevarría3,22,23, Isabel Morales-Muñoz3,24, Roberto Rodriguez-Jimenez3,24, Anna Butjosa3,25, Judith Usall Rodie3,25, Salvador Sarró26, Ramón Landín-Romero26, Angela Ibañez Cuadrado3,10, Manuel J Cuesta27,28, Vicent Balanzá-Martínez.3,29 13Department of Psychiatry, Hospital General Universitario Gregorio Marañón, School of Medicine, Universidad Complutense, Madrid, Spain; 14Child and Adolescent Psychiatry Department, Hospital General Universitario Gregorio Marañón, School of Medicine, Universidad Complutense, IiSGM, Madrid, Spain; 15Clinic Hospital Valencia, INCLIVA, Valencia University, Valencia Spain; 16IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain; 17Institut de Neuropsiquiatria i Addiccions, Hospital del Mar, Barcelona, Spain; 18Bipolar Disorders Unit, Hospital Clínic, University of Barcelona, Barcelona, Spain; 19Child and adolescent Psychiatry and Psychology Department, Hospital Clínic de Barcelona, SGR-489, Barcelona, Spain; 20Department of Psychiatry, Bellvitge University Hospital-IDIBELL, Barcelona, Spain; 21Department of Clinical Sciences, School of Medicine, University of Barcelona, Barcelona, Spain; 22Department of Psychiatry, University of Oviedo, Oviedo, Spain; 23Department of Neurosciences, BioCruces Health Research Institute, University of the Basque Country (UPV/EHU), Barakaldo, Spain; 24Department of Psychiatry, Cruces University Hospital, Barakaldo, Spain; 25Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain; 26Parc Sanitari Sant Joan de Déu, Sant Boi de Llobregat, Barcelona, Spain; 27FIDMAG Hermanas Hospitalarias Research Foundation, Barcelona, Spain; 28Psychiatric Department, Complejo Hospitalario de Navarra, Pamplona, Spain; 29Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain and 30Mental Health Centre of Catarroja, University of Valencia, Valencia, Spain.

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Mas, S., Gassó, P., Lafuente, A. et al. Pharmacogenetic study of antipsychotic induced acute extrapyramidal symptoms in a first episode psychosis cohort: role of dopamine, serotonin and glutamate candidate genes. Pharmacogenomics J 16, 439–445 (2016). https://doi.org/10.1038/tpj.2016.44

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