Influence of Glutamate Neurotransmission Genes on the Outcomes of Antipsychotic Treatments

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...

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Detalles Bibliográficos
Autores: Cendrós, Marc, Catalán, Rosa|||0000-0001-7003-2401, Torra, Mercè, Penadés, Rafael|||0000-0002-1564-3717, González-Rodríguez, Alexandre|||0000-0003-1855-8566, Brunet, Mercè|||0000-0002-7154-916X, Perez Blanco, Josefina|||0000-0002-6489-8871, Cullell, Natalia|||0000-0001-5118-1014, Serra-Llovich, Alexandre|||0000-0001-8318-851X, Hernandez, Marta H., Arranz, María Jesús|||0000-0002-6757-9198
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:319816
Acceso en línea:https://ddd.uab.cat/record/319816
https://dx.doi.org/urn:doi:10.1055/a-2603-0871
Access Level:acceso abierto
Palabra clave:Pharmacogenetics
Psychiatry
Schizophrenia
Glutamate
Antipsychotics
Descripción
Sumario: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. 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. 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. Our results suggest that genetic variation in glutamatergic pathways can influence the efficacy and safety of antipsychotic drugs.

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