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NMDA receptor function

What is NMDA receptor function?

Converging evidence suggests that N-methyl-d-aspartate (NMDA) receptor hypofunction may contribute to the expression of schizophrenia. The NMDA receptor consists of several subunits; the NR1 subunits that bind coagonists glycine and d-serine, the NR2 subunits that bind the neurotransmitter glutamate, and the NR3 subunits that bind glycine. The NMDA receptor is activated by binding glutamate and a coagonist. Glutamate is the major excitatory neurotransmitter in the brain and is crucial to normal brain function. In schizophrenia, there may be changes in levels of glutamate and its metabolites, and changes in levels or activity of mechanical components of the NMDA receptor system, such as the receptors that ‘receive’ glutamate, or the transporters that ‘remove’ it.

What is the evidence for NMDA receptor function?

Moderate to high quality evidence suggests medium-sized increases in peripheral glutamate as measured in serum or plasma in people with schizophrenia compared to controls. The effect is largest in drug-naïve or non-medicated patients and in studies using high-performance liquid chromatography to measure glutamate. There were small to medium-sized decreases in glutamate as measured using Magnetic Resonance Spectroscopy, and increases in glutamine in the frontal cortex of people with schizophrenia. There was also a medium-sized decrease in glutamate in the thalamus of people at clinical high risk, and a medium-sized increase in glutamate+glutamine in the frontal lobe of people at genetic high risk. Moderate quality evidence finds medium-sized decreases of NR1 mRNA expression and protein levels, and increases in blood serine levels in people with schizophrenia.

October 2020

Last updated at: 4:25 am, 23rd October 2020
To view documentation related to this topic download the files below
Fact Sheet Technical Commentary

NeuRA Libraries

Title Colour Legend:
Green - Topic summary is available.
Orange - Topic summary is being compiled.
Red - Topic summary has no current systematic review available.