Influence of Glutamate Neurotransmission Genes on the Outcomes of Antipsychotic Treatments
Por:
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
Publicada:
1 sep 2025
Ahead of Print:
1 jun 2025
Resumen:
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.
Filiaciones:
Cendrós, M:
Eugenom SL, Barcelona, Spain
Fundacio Docencia & Recerca Mutua Terrassa, Terrassa, Spain
Catalán, R:
Inst Recerca Biomed St Pau IIB St Pau, Ctr Invest Biomed Red Salud Mental CIBERSAM, Barcelona, Spain
Univ Barcelona, Hosp Clin Barcelona, Barcelona Clin Schizophrenia Unit BCSU, IDIBAPS,Neurosci Inst, Barcelona, Spain
Torra, M:
Hosp Clin Barcelona, Dept Biochem & Mol Genet, Pharmacol & Toxicol Unit, Barcelona, Spain
Penadés, R:
Inst Recerca Biomed St Pau IIB St Pau, Ctr Invest Biomed Red Salud Mental CIBERSAM, Barcelona, Spain
Univ Barcelona, Hosp Clin Barcelona, Barcelona Clin Schizophrenia Unit BCSU, IDIBAPS,Neurosci Inst, Barcelona, Spain
González-Rodríguez, A:
Univ Barcelona, Mutua Terrassa Univ Hosp, Fundacio Docencia & Recerca Mutua Terrassa, CIBERSAM,Dept Mental Hlth, Terrassa, Barcelona, Spain
Brunet, M:
Hosp Clin Barcelona, Dept Biochem & Mol Genet, Pharmacol & Toxicol Unit, Barcelona, Spain
Perez-Blanco, J:
Inst Recerca Biomed St Pau IIB St Pau, Ctr Invest Biomed Red Salud Mental CIBERSAM, Barcelona, Spain
Hosp Santa Creu & Sant Pau, Dept Psychiat, Barcelona, Spain
Cullell, N:
Fundacio Docencia & Recerca Mutua Terrassa, Terrassa, Spain
Serra-Llovich, A:
Fundacio Docencia & Recerca Mutua Terrassa, Terrassa, Spain
Hernandez, MH:
Fundacio Docencia & Recerca Mutua Terrassa, Terrassa, Spain
Univ Ramon Llull, Sch Hlth Sci Blanquerna, Barcelona, Spain
Arranz, MJ:
Fundacio Docencia & Recerca Mutua Terrassa, Terrassa, Spain
Inst Recerca Biomed St Pau IIB St Pau, Ctr Invest Biomed Red Salud Mental CIBERSAM, Barcelona, Spain
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