Effect of glutamate transporter EAAT2 gene variants and gray matter deficits on working memory in schizophrenia.
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.
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. Electronic address: poletti.sara@hsr.it.
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Poletti
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.
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Radaelli
Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy.
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Bosia
Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy.
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Buonocore
Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy.
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Pirovano
Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy.
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Lorenzi
Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy.
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Cavallaro
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.
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Smeraldi
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.
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Benedetti
D000328:Adult; D001921:Brain / Q000473:pathology*; D027342:Excitatory Amino Acid Transporter 2; D005260:Female; D050491:Glutamate Plasma Membrane Transport Proteins / Q000235:genetics*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term; D059906:Neuroimaging; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology; D012565:Schizophrenic Psychology
D027342:Excitatory Amino Acid Transporter 2; D050491:Glutamate Plasma Membrane Transport Proteins; C493397:SLC1A2 protein, human
EAAT2; Glutamate; Schizophrenia; Structural imaging; Working memory