Influence of Glutamate Neurotransmission Genes on the Outcomes of Antipsychotic Treatments

Introduction Traditionally, the aetiology of schizophrenia has been attributed to dopaminergic neurotransmission, but more recent information points to the role of glutamate pathways. Glutamatergic involvement in schizophrenia might be extensible to drug response. The aim of the study was to explore...

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Detalhes bibliográficos
Autores: Cendrós, M, Catalán, R, Torra, M, Penadés, R, González-Rodríguez, A, Brunet, M, Perez-Blanco, J, Cullell, N, Serra-Llovich, A, Hernandez, MH, Arranz, MJ
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Recursos:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositorio:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p20166
Acesso em linha:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=20166
Access Level:acceso abierto
Palavra-chave:pharmacogenetics
psychiatry
schizophrenia
glutamate
antipsychotics
Descrição
Resumo:Introduction Traditionally, the aetiology of schizophrenia has been attributed to dopaminergic neurotransmission, but more recent information points to the role of glutamate pathways. Glutamatergic involvement in schizophrenia might be extensible to drug response. The aim of the study was to explore whether the variation in glutamate receptors, transporters and metabolism can influence the outcome of drug treatments. Methods A total of 45 polymorphisms in the genes GRIN1, GRIN2A, GRIN2B, GRIN3A, GRIA1, GRIK2, GRM2, GRM3, GRM5, GRM8, SLC1A1, SLC1A3 and GAD1 were genotyped in 258 patients with schizophrenia. Efficacy and side effects were evaluated with the Positive and Negative Symptoms Scale and the UKU scale, respectively, at baseline and after 12 weeks. Results The analysis revealed associations between outcomes, including response and adverse effects and genetic variants in several genes (GAD1, GRIA1, GRIN2A, GRIN3A, GRIK2, GRM2, GRM5, GRM8 and SLC1A3). An association of rs1864205 in GRIA1 with autonomic side effects bordered statistical significance after correction for multiple comparisons. Discussion Our results suggest that genetic variation in glutamatergic pathways can influence the efficacy and safety of antipsychotic drugs.