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. 2025 Sep;58(5):205-215.
doi: 10.1055/a-2603-0871. Epub 2025 Jun 17.

Influence of Glutamate Neurotransmission Genes on the Outcomes of Antipsychotic Treatments

Marc Cendrós  1   2 , Rosa Catalán  3   4 , Mercè Torra  5 , Rafael Penadés  3   4 , Alexandre González-Rodríguez  6 , Mercè Brunet  5 , Josefina Perez-Blanco  3   7 , Natalia Cullell  2 , Alexandre Serra-Llovich  2 , Marta H Hernandez  2   8 , María J Arranz  2   3
Affiliations

Influence of Glutamate Neurotransmission Genes on the Outcomes of Antipsychotic Treatments

Marc Cendrós et al. Pharmacopsychiatry. 2025 Sep.

Abstract

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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Conflict of interest statement

Marc Cendrós is employed by Eugenomic S.L., a company that offers testing, counselling and data interpretation on pharmacogenetics. The company was not involved in the study, and did not have any influence in any way on the results.

References

    1. Institute of health Metrics and Evaluation (IHME). Global Health Data Exchange (GHDx)http://ghdx.healthdata.org/gbd-results-tool?params=gbd-api-2019-permalin...
    1. Howes O D, Kapur S. The dopamine hypothesis of schizophrenia: Version III--the final common pathway. Schizophr Bull. 2009;35:549–562. doi: 10.1093/schbul/sbp006. - DOI - PMC - PubMed
    1. Madras B K. History of the discovery of the antipsychotic dopamine D2 receptor: A basis for the dopamine hypothesis of schizophrenia. J Hist Neurosci. 2013;22:62–78. doi: 10.1080/0964704X.2012.678199. - DOI - PubMed
    1. Nord M, Farde L. Antipsychotic occupancy of dopamine receptors in schizophrenia. CNS Neurosci Ther. 2011;17:97–103. doi: 10.1111/j.1755-5949.2010.00222.x. - DOI - PMC - PubMed
    1. Uno Y, Coyle J T. Glutamate hypothesis in schizophrenia. Psychiatry Clin Neurosci. 2019;73:204–215. doi: 10.1111/pcn.12823. - DOI - PubMed