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CC BY 4.0 · Pharmacopsychiatry
DOI: 10.1055/a-2603-0871
Original Paper

Influence of Glutamate Neurotransmission Genes on the Outcomes of Antipsychotic Treatments

Marc Cendrós
1   Eugenomic S.L., Barcelona, Spain
2   Fundació Docència i Recerca Mútua Terrassa Terrassa, Spain
,
Rosa Catalán    #
3   Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Institut de Recerca Biomèdica Sant Pau (IIB-Sant Pau), Barcelona, Spain
4   Barcelona Clinic Schizophrenia Unit (BCSU), Neurosciences Institute, Hospital Clínic of Barcelona, University of Barcelona, IDIBAPS, Barcelona, Spain
,
Mercè Torra
5   Pharmacology & Toxicology Unit, Dept. Biochemistry & Molecular Genetics, Hospital Clínic of Barcelona, Barcelona, Spain
,
Rafael Penadés
3   Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Institut de Recerca Biomèdica Sant Pau (IIB-Sant Pau), Barcelona, Spain
4   Barcelona Clinic Schizophrenia Unit (BCSU), Neurosciences Institute, Hospital Clínic of Barcelona, University of Barcelona, IDIBAPS, Barcelona, Spain
,
Alexandre González-Rodríguez
6   Dept. Mental Health, Mutua Terrassa University Hospital, Fundació Docència i Recerca Mutua Terrassa, University of Barcelona, CIBERSAM, Barcelona, Terrassa, Spain
,
Mercè Brunet
5   Pharmacology & Toxicology Unit, Dept. Biochemistry & Molecular Genetics, Hospital Clínic of Barcelona, Barcelona, Spain
,
Josefina Perez-Blanco
3   Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Institut de Recerca Biomèdica Sant Pau (IIB-Sant Pau), Barcelona, Spain
7   Dept. Psychiatry, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
,
Natalia Cullell
2   Fundació Docència i Recerca Mútua Terrassa Terrassa, Spain
,
Alexandre Serra-Llovich
2   Fundació Docència i Recerca Mútua Terrassa Terrassa, Spain
,
Marta H. Hernandez
2   Fundació Docència i Recerca Mútua Terrassa Terrassa, Spain
8   School of Health Sciences Blanquerna, University Ramon Llull, Barcelona, Spain
,
María J. Arranz    #
2   Fundació Docència i Recerca Mútua Terrassa Terrassa, Spain
3   Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Institut de Recerca Biomèdica Sant Pau (IIB-Sant Pau), Barcelona, Spain
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Abstract

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.

Keywords

pharmacogenetics - psychiatry - schizophrenia - glutamate - antipsychotics

# These authors are equal corresponding authors: María J. Arranz and Rosa Catalán




Publication History

Received: 24 April 2024

Accepted: 27 February 2025

Article published online:
17 June 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).

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