N-methyl-D-aspartate receptor availability in first-episode psychosis a PET-MR brain imaging study.pdf (1.78 MB)
N-methyl-D-aspartate receptor availability in first-episode psychosis: a PET-MR brain imaging study
journal contribution
posted on 2023-06-10, 01:05 authored by Katherine Beck, Atheeshaan Arumuham, Mattia Veronese, Barbara Santangelo, Colm J McGinnity, Joel Dunn, Robert A McCutcheon, Stephen J Kaar, Nisha Singh, Toby Pillinger, Faith Borgan, James StoneJames Stone, Sameer Jauhar, Teresa Sementa, Federico Turkheimer, Alexander Hammers, Oliver D HowesN-methyl-D-aspartate receptor (NMDAR) hypofunction is hypothesised to underlie psychosis but this has not been tested early in illness. To address this, we studied 40 volunteers (21 patients with first-episode psychosis and 19 matched healthy controls) using PET imaging with an NMDAR selective ligand, [18F]GE-179, that binds to the ketamine binding site to index its distribution volume ratio (DVR) and volume of distribution (VT). Hippocampal DVR, but not VT, was significantly lower in patients relative to controls (p = 0.02, Cohen’s d = 0.81; p = 0.15, Cohen’s d = 0.49), and negatively associated with total (rho = -0.47, p = 0.04), depressive (rho = -0.67, p = 0.002), and general symptom severity (rho = -0.74, p < 0.001). Exploratory analyses found no significant differences in other brain regions (anterior cingulate cortex, thalamus, striatum and temporal cortex). These findings are consistent with the NMDAR hypofunction hypothesis and identify the hippocampus as a key locus for relative NMDAR hypofunction, although further studies should test specificity and causality.
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Publication status
- Published
File Version
- Published version
Journal
Translational PsychiatryISSN
2158-3188Publisher
Springer NatureExternal DOI
Issue
1Volume
11Page range
1-8Article number
a425Event location
United StatesDepartment affiliated with
- BSMS Neuroscience Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2021-09-23First Open Access (FOA) Date
2021-09-23First Compliant Deposit (FCD) Date
2021-09-22Usage metrics
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