I came across this paper in the twitter feed of Bita Moghaddam, a famous researcher known for her glutamate hypothesis of schizophrenia and her work on the NMDA receptor and glutamate signaling.
Quote:
“New preprint. Super excited about this data because almost 30 years after our series of papers on dopamine, NMDA, and schizophrenia came out, we may have mechanistic insight about latent presentation of psychosis and abnormalities in dopamine dynamics in schizophrenia”
She goes on with a thread of tweets after that.
The actual paper is here:
Abstract:
Psychosis is a hallmark of schizophrenia. It typically emerges in late adolescence and is associated with dopamine abnormalities and aberrant salience. Most genes associated with schizophrenia risk involve ubiquitous targets that may not explain delayed emergence of dopaminergic disruptions. This includes GRIN2A, the gene encoding the GluN2A subunit of the NMDA receptor. Both common and rare variants of GRIN2A are considered genetic risk factors for schizophrenia diagnosis. We find that Grin2a knockout in dopamine neurons during adolescence is sufficient to produce a behavioral phenotype that mirrors aspects of psychosis. These include disruptions in effort optimization, salience attribution, and ability to utilize feedback to guide behavior. We also find a selective effect of this manipulation on dopamine release during prediction error signaling. These data provide mechanistic insight into how variants of GRIN2A may lead to the latent presentation of aberrant salience and abnormalities in dopamine dynamics. This etiologically relevant model may aid future discovery of course altering treatments for schizophrenia.
See also:
- GRIN2A at Wikipedia
- Bita Moghaddam - Wikipedia
- Glutamate hypothesis of schizophrenia - Wikipedia