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Effect of glutamate transporter EAAT2 gene variants and gray matter deficits on working memory in schizophrenia

Published online by Cambridge University Press:  15 April 2020

S. Poletti ,
D. Radaelli ,
M. Bosia ,
M. Buonocore ,
A. Pirovano ,
C. Lorenzi ,
R. Cavallaro ,
E. Smeraldi  and
F. Benedetti
S. Poletti*
Affiliation:
Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy Centro di Eccellenza Risonanza Magnetica ad Alto Campo (CERMAC), University Vita-Salute San Raffaele, Milan, Italy
D. Radaelli
Affiliation:
Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy Centro di Eccellenza Risonanza Magnetica ad Alto Campo (CERMAC), University Vita-Salute San Raffaele, Milan, Italy
M. Bosia
Affiliation:
Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy
M. Buonocore
Affiliation:
Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy
A. Pirovano
Affiliation:
Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy
C. Lorenzi
Affiliation:
Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy
R. Cavallaro
Affiliation:
Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy
E. Smeraldi
Affiliation:
Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy Centro di Eccellenza Risonanza Magnetica ad Alto Campo (CERMAC), University Vita-Salute San Raffaele, Milan, Italy
F. Benedetti
Affiliation:
Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy Centro di Eccellenza Risonanza Magnetica ad Alto Campo (CERMAC), University Vita-Salute San Raffaele, Milan, Italy
*
*Corresponding author. Istituto Scientifico Ospedale San Raffaele, Department of Clinical Neurosciences, San Raffaele Turro, Via Stamira d’Ancona 20, Milano, Italy. Tel.: +39 02 26433156; fax: +39 02 26433265. E-mail address: poletti.sara@hsr.it (S. Poletti).
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Abstract

Glutamate is the major excitatory neurotransmitter in the brain, with up to 40% of all synapses being glutamatergic. An altered glutamatergic transmission could play a critical role in working memory deficts observed in schizophrenia and could underline progressive changes such as grey matter loss throughout the brain. The aim of the study was to investigate if gray matter volume and working memory could be modulated by a genetic polymorphism related to glutamatergic function. Fifty schizophrenia patients underwent magnetic resonance and working memory testing outside of the scanner and were genotyped for rs4354668 EAAT2 polymorphism. Carriers of the G allele had lower gray matter volumes than T/T homozygote and worse working memory performance. Poor working memory performance was associated with gray matter reduction. Differences between the three genotypes are more relevant among patients showing poor performance at the 2-back task. Since glutamate abnormalities are known to be involved in excitotoxic processes, the decrease in cortical thickness observed in schizophrenia patients could be linked to an excess of extracellular glutamate. The differential effect of EAAT2 observed between good and poor performers suggests that the effect of EEAT2 on gray matter might reveal in the presence of a pathological process affecting gray matter.

Keywords

SchizophreniaEAAT2GlutamateWorking memoryStructural imaging
Type
Original articles
Information
European Psychiatry , Volume 29 , Issue 4 , May 2014 , pp. 219 - 225
Copyright
Copyright © European Psychiatric Association 2014

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Footnotes

Abbreviation: EAAT, Excitatory amino-acid transporter

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