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Brain volume in chronic ketamine users — relationship to sub-threshold psychotic symptoms and relevance to schizophrenia

RATIONALE: Ketamine may model aspects of schizophrenia arising through NMDA receptor activity deficits. Although acute ketamine can induce effects resembling both positive and negative psychotic symptoms, chronic use may be a closer model of idiopathic psychosis. OBJECTIVES: We tested the hypotheses...

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Autores principales: Chesters, Robert A., Pepper, Fiona, Morgan, Celia, Cooper, Jonathan D., Howes, Oliver D., Vernon, Anthony C., Stone, James M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9584979/
https://www.ncbi.nlm.nih.gov/pubmed/34228135
http://dx.doi.org/10.1007/s00213-021-05873-0
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author Chesters, Robert A.
Pepper, Fiona
Morgan, Celia
Cooper, Jonathan D.
Howes, Oliver D.
Vernon, Anthony C.
Stone, James M.
author_facet Chesters, Robert A.
Pepper, Fiona
Morgan, Celia
Cooper, Jonathan D.
Howes, Oliver D.
Vernon, Anthony C.
Stone, James M.
author_sort Chesters, Robert A.
collection PubMed
description RATIONALE: Ketamine may model aspects of schizophrenia arising through NMDA receptor activity deficits. Although acute ketamine can induce effects resembling both positive and negative psychotic symptoms, chronic use may be a closer model of idiopathic psychosis. OBJECTIVES: We tested the hypotheses that ketamine users had lower brain volumes, as measured using MRI, and greater sub-threshold psychotic symptoms relative to a poly-drug user control group. METHODS: Ketamine users (n = 17) and poly-drug using controls (n = 19) were included in the study. All underwent volumetric MRI imaging and measurement of sub-threshold psychotic symptoms using the Comprehensive Assessment of At-Risk Mental State (CAARMS). Freesurfer was used to analyse differences in regional brain volume, cortical surface area and thickness between ketamine users and controls. The relationship between CAARMS ratings and brain volume was also investigated in ketamine users. RESULTS: Ketamine users were found to have significantly lower grey matter volumes of the nucleus accumbens, caudate nucleus, cerebellum and total cortex (FDR p < 0.05; Cohen’s d = 0.36–0.75). Within the cortex, ketamine users had significantly lower grey matter volumes within the frontal, temporal and parietal cortices (Cohen’s d 0.7–1.31; FDR p < 0.05). They also had significantly higher sub-threshold psychotic symptoms (p < 0.05). Frequency of ketamine use showed an inverse correlation with cerebellar volume (p < 0.001), but there was no relationship between regional brain volumes and sub-threshold psychotic symptoms. CONCLUSIONS: Chronic ketamine use may cause lower grey matter volumes as well as inducing sub-threshold psychotic symptoms, although these likely arise through distinct mechanisms. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00213-021-05873-0.
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spelling pubmed-95849792022-10-22 Brain volume in chronic ketamine users — relationship to sub-threshold psychotic symptoms and relevance to schizophrenia Chesters, Robert A. Pepper, Fiona Morgan, Celia Cooper, Jonathan D. Howes, Oliver D. Vernon, Anthony C. Stone, James M. Psychopharmacology (Berl) Original Investigation RATIONALE: Ketamine may model aspects of schizophrenia arising through NMDA receptor activity deficits. Although acute ketamine can induce effects resembling both positive and negative psychotic symptoms, chronic use may be a closer model of idiopathic psychosis. OBJECTIVES: We tested the hypotheses that ketamine users had lower brain volumes, as measured using MRI, and greater sub-threshold psychotic symptoms relative to a poly-drug user control group. METHODS: Ketamine users (n = 17) and poly-drug using controls (n = 19) were included in the study. All underwent volumetric MRI imaging and measurement of sub-threshold psychotic symptoms using the Comprehensive Assessment of At-Risk Mental State (CAARMS). Freesurfer was used to analyse differences in regional brain volume, cortical surface area and thickness between ketamine users and controls. The relationship between CAARMS ratings and brain volume was also investigated in ketamine users. RESULTS: Ketamine users were found to have significantly lower grey matter volumes of the nucleus accumbens, caudate nucleus, cerebellum and total cortex (FDR p < 0.05; Cohen’s d = 0.36–0.75). Within the cortex, ketamine users had significantly lower grey matter volumes within the frontal, temporal and parietal cortices (Cohen’s d 0.7–1.31; FDR p < 0.05). They also had significantly higher sub-threshold psychotic symptoms (p < 0.05). Frequency of ketamine use showed an inverse correlation with cerebellar volume (p < 0.001), but there was no relationship between regional brain volumes and sub-threshold psychotic symptoms. CONCLUSIONS: Chronic ketamine use may cause lower grey matter volumes as well as inducing sub-threshold psychotic symptoms, although these likely arise through distinct mechanisms. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00213-021-05873-0. Springer Berlin Heidelberg 2021-07-06 2022 /pmc/articles/PMC9584979/ /pubmed/34228135 http://dx.doi.org/10.1007/s00213-021-05873-0 Text en © The Author(s) 2021, corrected publication 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Investigation
Chesters, Robert A.
Pepper, Fiona
Morgan, Celia
Cooper, Jonathan D.
Howes, Oliver D.
Vernon, Anthony C.
Stone, James M.
Brain volume in chronic ketamine users — relationship to sub-threshold psychotic symptoms and relevance to schizophrenia
title Brain volume in chronic ketamine users — relationship to sub-threshold psychotic symptoms and relevance to schizophrenia
title_full Brain volume in chronic ketamine users — relationship to sub-threshold psychotic symptoms and relevance to schizophrenia
title_fullStr Brain volume in chronic ketamine users — relationship to sub-threshold psychotic symptoms and relevance to schizophrenia
title_full_unstemmed Brain volume in chronic ketamine users — relationship to sub-threshold psychotic symptoms and relevance to schizophrenia
title_short Brain volume in chronic ketamine users — relationship to sub-threshold psychotic symptoms and relevance to schizophrenia
title_sort brain volume in chronic ketamine users — relationship to sub-threshold psychotic symptoms and relevance to schizophrenia
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9584979/
https://www.ncbi.nlm.nih.gov/pubmed/34228135
http://dx.doi.org/10.1007/s00213-021-05873-0
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