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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

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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 Howes
N-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.

History

Publication status

  • Published

File Version

  • Published version

Journal

Translational Psychiatry

ISSN

2158-3188

Publisher

Springer Nature

Issue

1

Volume

11

Page range

1-8

Article number

a425

Event location

United States

Department affiliated with

  • BSMS Neuroscience Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2021-09-23

First Open Access (FOA) Date

2021-09-23

First Compliant Deposit (FCD) Date

2021-09-22

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