N-Methyl-D-Aspartate Receptor availability in First-Episode Psychosis: a multi-modal PET-MR brain imaging study
K. Beck, A. Arumuham, S. Brugger, R. Mccutcheon, M. Veronese, S. Kaar, T. Pillinger, J. Stone, O. Howes
European Psychiatry November 17, 2023 Peer reviewed DOI: 10.1192/j.eurpsy.2022.238 via DOAJ
Summary
Patients with first episode psychosis showed significantly lower N-Methyl-D-Aspartate Receptor (NMDAR) availability in the hippocampus compared to healthy controls, with a distribution volume ratio (DVR) that was negatively associated with symptom severity. Specifically, the hippocampal DVR was lower in patients (Cohen’s d=0.81), while no significant differences were observed in other brain regions. An inverse relationship between hippocampal NMDAR availability and striatal glutamate levels was found in patients but not in controls.
Study at a glance
| Design | observational cohort |
|---|---|
| Sample size | 40 |
| Population | 21 patients with first episode psychosis and 19 matched healthy controls |
| Key finding | Hippocampal NMDAR availability was significantly lower in patients with first episode psychosis compared to healthy controls. |
Abstract
Introduction N-Methyl-D-Aspartate Receptor (NMDAR) hypofunction is hypothesised to underlie psychosis but this has not been tested early in illness. Objectives Our aim was to determine if NMDAR availability was lower in patients with first episode psychosis compared to healthy controls. Methods 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]GE179, that binds to the ketamine binding site to index its distribution volume ratio (DVR) and volume of distribution (VT). Striatal glutamatergic indices (glutamate and Glx) were measured simultaneously using magnetic resonance spectroscopy imaging (1H-MRS). Results 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). We found an inverse relationship between hippocampal NMDAR availability and striatal glutamate levels in people with first-episode psychosis (rho = -0.74, p <0.001) but not in healthy controls (rho = -0.22, p = 0.44). Conclusions 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. Disclosure No significant relationships.