The glutamate hypothesis of schizophrenia: neuroimaging and drug development.

Abstract:

:Over the last 50 years, evidence for central involvement of glutamatergic neurotransmission in the pathophysiology of schizophrenia has accumulated. Recent advances in neuroimaging technology now allow several components of glutamatergic neurotransmission to be assessed in the living human brain. Positron emission tomography (PET) or single photon emission tomography (SPET) in combination with select radiotracers allows visualization of glutamatergic receptors in vivo, and magnetic resonance (MR) - based techniques allow mapping of the effects of glutamatergic agents on regional brain activation, and the measurement of regional glutamate concentrations. These imaging studies have provided evidence for regional glutamatergic abnormalities in psychosis, and are beginning to describe both the evolution of these abnormalities over the course of the illness and their response to therapeutic intervention. In parallel, advances in small animal imaging and the development of animal models have provided a platform to explore the neuropathological consequences of glutamatergic abnormality, and the potential antipsychotic efficacy of novel compounds. The molecular diversity of the glutamatergic system has driven the design of several compounds targeting aspects of glutamatergic transmission, and clinical trials have yielded encouraging results. Here, we review the contribution of imaging studies to date in understanding glutamatergic abnormalities in psychosis, and discuss the potential of new glutamatergic compounds for treatment of the disorder.

journal_name

Curr Pharm Biotechnol

authors

Egerton A,Stone JM

doi

10.2174/138920112800784961

subject

Has Abstract

pub_date

2012-06-01 00:00:00

pages

1500-12

issue

8

eissn

1389-2010

issn

1873-4316

pii

CPB-EPUB-20120126-002

journal_volume

13

pub_type

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