Influence of Glutamate Neurotransmission Genes on the Outcomes of
                    Antipsychotic Treatments

Marc Cendrós; Rosa Catalán; Mercè Torra; Rafael Penadés; Alexandre González-Rodríguez; Mercè Brunet; Josefina Perez-Blanco; Natalia Cullell; Alexandre Serra-Llovich; Marta H. Hernandez; María J. Arranz

doi:10.1055/a-2603-0871

Pharmacopsychiatry, Inhaltsverzeichnis

CC BY 4.0 · Pharmacopsychiatry 2025; 58(05): 205-215
DOI: 10.1055/a-2603-0871

Original Paper

Influence of Glutamate Neurotransmission Genes on the Outcomes of Antipsychotic Treatments

Marc Cendrós

¹Eugenomic S.L., Barcelona, Spain

²Fundació Docència i Recerca Mútua Terrassa Terrassa, Spain

,

Rosa Catalán ^#

³Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Institut de Recerca Biomèdica Sant Pau (IIB-Sant Pau), Barcelona, Spain

⁴Barcelona Clinic Schizophrenia Unit (BCSU), Neurosciences Institute, Hospital Clínic of Barcelona, University of Barcelona, IDIBAPS, Barcelona, Spain

,

Mercè Torra

⁵Pharmacology & Toxicology Unit, Dept. Biochemistry & Molecular Genetics, Hospital Clínic of Barcelona, Barcelona, Spain

,

Rafael Penadés

³Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Institut de Recerca Biomèdica Sant Pau (IIB-Sant Pau), Barcelona, Spain

⁴Barcelona Clinic Schizophrenia Unit (BCSU), Neurosciences Institute, Hospital Clínic of Barcelona, University of Barcelona, IDIBAPS, Barcelona, Spain

,

Alexandre González-Rodríguez

⁶Dept. Mental Health, Mutua Terrassa University Hospital, Fundació Docència i Recerca Mutua Terrassa, University of Barcelona, CIBERSAM, Barcelona, Terrassa, Spain

,

Mercè Brunet

⁵Pharmacology & Toxicology Unit, Dept. Biochemistry & Molecular Genetics, Hospital Clínic of Barcelona, Barcelona, Spain

,

Josefina Perez-Blanco

³Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Institut de Recerca Biomèdica Sant Pau (IIB-Sant Pau), Barcelona, Spain

⁷Dept. Psychiatry, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

,

Natalia Cullell

²Fundació Docència i Recerca Mútua Terrassa Terrassa, Spain

,

Alexandre Serra-Llovich

²Fundació Docència i Recerca Mútua Terrassa Terrassa, Spain

,

Marta H. Hernandez

²Fundació Docència i Recerca Mútua Terrassa Terrassa, Spain

⁸School of Health Sciences Blanquerna, University Ramon Llull, Barcelona, Spain

,

María J. Arranz ^#

²Fundació Docència i Recerca Mútua Terrassa Terrassa, Spain

³Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Institut de Recerca Biomèdica Sant Pau (IIB-Sant Pau), Barcelona, Spain

› Institutsangaben

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

Volltext

Referenzen

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