N-methyl-D-aspartate receptor availability in first-episode psychosis: a PET-MR brain imaging study
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 Stone, Sameer Jauhar, Teresa Sementa, Federico Turkheimer, Alexander Hammers, Oliver Howes
Translational Psychiatry August 15, 2021 DOI: 10.1038/s41398-021-01540-2 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Case-control study Peer reviewed |
|---|---|
| Sample size | 40 |
| Population | 21 patients with first-episode psychosis and 19 matched healthy controls |
| Key findings | Hippocampal NMDAR availability, indexed by [18F]GE-179 distribution volume ratio, was significantly lower in patients with first-episode psychosis than in healthy controls (Cohen's d = 0.81) and was negatively associated with total, depressive, and general symptom severity. The authors argue these findings are consistent with the NMDAR hypofunction hypothesis and identify the hippocampus as a key locus, though they note specificity and causality require further study. |
Abstract
Abstract 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 (V T). Hippocampal DVR, but not V T, 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.