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Glutamate in schizophrenia: Neurodevelopmental perspectives and drug development

Research output: Contribution to journalReview articlepeer-review

Alice Egerton, Anthony A Grace, James Stone, Matthias Bossong, Michael Sand, Philip McGuire

Original languageEnglish
JournalSchizophrenia Research
Early online date16 Oct 2020
Accepted/In press20 Sep 2020
E-pub ahead of print16 Oct 2020
Published3 Dec 2020


King's Authors


Research into the neurobiological processes that may lead to the onset of schizophrenia places growing emphasis on the glutamatergic system and brain development. Preclinical studies have shown that neurodevelopmental, genetic, and environmental factors contribute to glutamatergic dysfunction and schizophrenia-related phenotypes. Clinical research has suggested that altered brain glutamate levels may be present before the onset of psychosis and relate to outcome in those at clinical high risk. After psychosis onset, glutamate dysfunction may also relate to the degree of antipsychotic response and clinical outcome. These findings support ongoing efforts to develop pharmacological interventions that target the glutamate system and could suggest that glutamatergic compounds may be more effective in specific patient subgroups or illness stages. In this review, we consider the updated glutamate hypothesis of schizophrenia, from a neurodevelopmental perspective, by reviewing recent preclinical and clinical evidence, and discuss the potential implications for novel therapeutics.

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