N-Methyl-D-Aspartate Receptor availability in First-Episode Psychosis: a multi-modal PET-MR brain imaging study
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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Cambridge University Press
2022-06-01
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| Series: | European Psychiatry |
| Subjects: | |
| Online Access: | https://www.cambridge.org/core/product/identifier/S0924933822002383/type/journal_article |
| _version_ | 1827754927670165504 |
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| author | K. Beck A. Arumuham S. Brugger R. Mccutcheon M. Veronese S. Kaar T. Pillinger J. Stone O. Howes |
| author_facet | K. Beck A. Arumuham S. Brugger R. Mccutcheon M. Veronese S. Kaar T. Pillinger J. Stone O. Howes |
| author_sort | K. Beck |
| collection | DOAJ |
| description |
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.
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| first_indexed | 2024-03-11T07:57:22Z |
| format | Article |
| id | doaj.art-036e2658f667440d914b2281607e3a59 |
| institution | Directory Open Access Journal |
| issn | 0924-9338 1778-3585 |
| language | English |
| last_indexed | 2024-03-11T07:57:22Z |
| publishDate | 2022-06-01 |
| publisher | Cambridge University Press |
| record_format | Article |
| series | European Psychiatry |
| spelling | doaj.art-036e2658f667440d914b2281607e3a592023-11-17T05:05:20ZengCambridge University PressEuropean Psychiatry0924-93381778-35852022-06-0165S77S7710.1192/j.eurpsy.2022.238N-Methyl-D-Aspartate Receptor availability in First-Episode Psychosis: a multi-modal PET-MR brain imaging studyK. Beck0A. Arumuham1S. Brugger2R. Mccutcheon3M. Veronese4S. Kaar5T. Pillinger6J. Stone7O. Howes8Institution of Psychiatry, Psychology & Neuroscience, Department Of Psychosis Studies, United Kingdom, United KingdomInstitution of Psychiatry, Psychology & Neuroscience, Department Of Psychosis Studies, United Kingdom, United KingdomCardiff University Brain Research Imaging Centre (CUBRIC), School Of Psychology, HQ, United KingdomInstitution of Psychiatry, Psychology & Neuroscience, Department Of Psychosis Studies, United Kingdom, United KingdomInstitution of Psychiatry, Psychology & Neuroscience, Department Of Psychosis Studies, United Kingdom, United KingdomInstitution of Psychiatry, Psychology & Neuroscience, Department Of Psychosis Studies, United Kingdom, United KingdomInstitution of Psychiatry, Psychology & Neuroscience, Department Of Psychosis Studies, United Kingdom, United KingdomBrighton and Sussex Medical School, University Of Sussex, Brighton, United KingdomInstitution of Psychiatry, Psychology & Neuroscience, Department Of Psychosis Studies, United Kingdom, United Kingdom 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. https://www.cambridge.org/core/product/identifier/S0924933822002383/type/journal_articlePsychosisNeuroimagingNMDARGlutamate |
| spellingShingle | K. Beck A. Arumuham S. Brugger R. Mccutcheon M. Veronese S. Kaar T. Pillinger J. Stone O. Howes N-Methyl-D-Aspartate Receptor availability in First-Episode Psychosis: a multi-modal PET-MR brain imaging study European Psychiatry Psychosis Neuroimaging NMDAR Glutamate |
| title | N-Methyl-D-Aspartate Receptor availability in First-Episode Psychosis: a multi-modal PET-MR brain imaging study |
| title_full | N-Methyl-D-Aspartate Receptor availability in First-Episode Psychosis: a multi-modal PET-MR brain imaging study |
| title_fullStr | N-Methyl-D-Aspartate Receptor availability in First-Episode Psychosis: a multi-modal PET-MR brain imaging study |
| title_full_unstemmed | N-Methyl-D-Aspartate Receptor availability in First-Episode Psychosis: a multi-modal PET-MR brain imaging study |
| title_short | N-Methyl-D-Aspartate Receptor availability in First-Episode Psychosis: a multi-modal PET-MR brain imaging study |
| title_sort | n methyl d aspartate receptor availability in first episode psychosis a multi modal pet mr brain imaging study |
| topic | Psychosis Neuroimaging NMDAR Glutamate |
| url | https://www.cambridge.org/core/product/identifier/S0924933822002383/type/journal_article |
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