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Prefrontal GABA levels, hippocampal resting perfusion and the risk of psychosis

Preclinical models propose that the onset of psychosis is associated with hippocampal hyperactivity, thought to be driven by cortical GABAergic interneuron dysfunction and disinhibition of pyramidal neurons. Recent neuroimaging studies suggest that resting hippocampal perfusion is increased in subje...

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Autores principales: Modinos, Gemma, Şimşek, Fatma, Azis, Matilda, Bossong, Matthijs, Bonoldi, Ilaria, Samson, Carly, Quinn, Beverly, Perez, Jesus, Broome, Matthew R, Zelaya, Fernando, Lythgoe, David J, Howes, Oliver D, Stone, James M, Grace, Anthony A, Allen, Paul, McGuire, Philip
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5955214/
https://www.ncbi.nlm.nih.gov/pubmed/29440719
http://dx.doi.org/10.1038/s41386-017-0004-6
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author Modinos, Gemma
Şimşek, Fatma
Azis, Matilda
Bossong, Matthijs
Bonoldi, Ilaria
Samson, Carly
Quinn, Beverly
Perez, Jesus
Broome, Matthew R
Zelaya, Fernando
Lythgoe, David J
Howes, Oliver D
Stone, James M
Grace, Anthony A
Allen, Paul
McGuire, Philip
author_facet Modinos, Gemma
Şimşek, Fatma
Azis, Matilda
Bossong, Matthijs
Bonoldi, Ilaria
Samson, Carly
Quinn, Beverly
Perez, Jesus
Broome, Matthew R
Zelaya, Fernando
Lythgoe, David J
Howes, Oliver D
Stone, James M
Grace, Anthony A
Allen, Paul
McGuire, Philip
author_sort Modinos, Gemma
collection PubMed
description Preclinical models propose that the onset of psychosis is associated with hippocampal hyperactivity, thought to be driven by cortical GABAergic interneuron dysfunction and disinhibition of pyramidal neurons. Recent neuroimaging studies suggest that resting hippocampal perfusion is increased in subjects at ultra-high risk (UHR) for psychosis, but how this may be related to GABA concentrations is unknown. The present study used a multimodal neuroimaging approach to address this issue in UHR subjects. Proton magnetic resonance spectroscopy and pulsed-continuous arterial spin labeling imaging were acquired to investigate the relationship between medial prefrontal (MPFC) GABA+ levels (including some contribution from macromolecules) and hippocampal regional cerebral blood flow (rCBF) in 36 individuals at UHR of psychosis, based on preclinical evidence that MPFC dysfunction is involved in hippocampal hyperactivity. The subjects were then clinically monitored for 2 years: during this period, 7 developed a psychotic disorder and 29 did not. At baseline, MPFC GABA+ levels were positively correlated with rCBF in the left hippocampus (region of interest analysis, p = 0.044 family-wise error corrected, FWE). This correlation in the left hippocampus was significantly different in UHR subjects who went on to develop psychosis relative to those who did not (p = 0.022 FWE), suggesting the absence of a correlation in the latter subgroup. These findings provide the first human evidence that MPFC GABA+ concentrations are related to resting hippocampal perfusion in the UHR state, and offer some support for a link between GABA levels and hippocampal function in the development of psychosis.
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spelling pubmed-59552142018-11-13 Prefrontal GABA levels, hippocampal resting perfusion and the risk of psychosis Modinos, Gemma Şimşek, Fatma Azis, Matilda Bossong, Matthijs Bonoldi, Ilaria Samson, Carly Quinn, Beverly Perez, Jesus Broome, Matthew R Zelaya, Fernando Lythgoe, David J Howes, Oliver D Stone, James M Grace, Anthony A Allen, Paul McGuire, Philip Neuropsychopharmacology Article Preclinical models propose that the onset of psychosis is associated with hippocampal hyperactivity, thought to be driven by cortical GABAergic interneuron dysfunction and disinhibition of pyramidal neurons. Recent neuroimaging studies suggest that resting hippocampal perfusion is increased in subjects at ultra-high risk (UHR) for psychosis, but how this may be related to GABA concentrations is unknown. The present study used a multimodal neuroimaging approach to address this issue in UHR subjects. Proton magnetic resonance spectroscopy and pulsed-continuous arterial spin labeling imaging were acquired to investigate the relationship between medial prefrontal (MPFC) GABA+ levels (including some contribution from macromolecules) and hippocampal regional cerebral blood flow (rCBF) in 36 individuals at UHR of psychosis, based on preclinical evidence that MPFC dysfunction is involved in hippocampal hyperactivity. The subjects were then clinically monitored for 2 years: during this period, 7 developed a psychotic disorder and 29 did not. At baseline, MPFC GABA+ levels were positively correlated with rCBF in the left hippocampus (region of interest analysis, p = 0.044 family-wise error corrected, FWE). This correlation in the left hippocampus was significantly different in UHR subjects who went on to develop psychosis relative to those who did not (p = 0.022 FWE), suggesting the absence of a correlation in the latter subgroup. These findings provide the first human evidence that MPFC GABA+ concentrations are related to resting hippocampal perfusion in the UHR state, and offer some support for a link between GABA levels and hippocampal function in the development of psychosis. Springer International Publishing 2018-01-30 2018-12 /pmc/articles/PMC5955214/ /pubmed/29440719 http://dx.doi.org/10.1038/s41386-017-0004-6 Text en © The Author(s) 2018 Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Modinos, Gemma
Şimşek, Fatma
Azis, Matilda
Bossong, Matthijs
Bonoldi, Ilaria
Samson, Carly
Quinn, Beverly
Perez, Jesus
Broome, Matthew R
Zelaya, Fernando
Lythgoe, David J
Howes, Oliver D
Stone, James M
Grace, Anthony A
Allen, Paul
McGuire, Philip
Prefrontal GABA levels, hippocampal resting perfusion and the risk of psychosis
title Prefrontal GABA levels, hippocampal resting perfusion and the risk of psychosis
title_full Prefrontal GABA levels, hippocampal resting perfusion and the risk of psychosis
title_fullStr Prefrontal GABA levels, hippocampal resting perfusion and the risk of psychosis
title_full_unstemmed Prefrontal GABA levels, hippocampal resting perfusion and the risk of psychosis
title_short Prefrontal GABA levels, hippocampal resting perfusion and the risk of psychosis
title_sort prefrontal gaba levels, hippocampal resting perfusion and the risk of psychosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5955214/
https://www.ncbi.nlm.nih.gov/pubmed/29440719
http://dx.doi.org/10.1038/s41386-017-0004-6
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