Adverse clinical outcomes in people at clinical high-risk for psychosis related to altered interactions between hippocampal activity and glutamatergic function

Abstract Preclinical rodent models suggest that psychosis involves alterations in the activity and glutamatergic function in the hippocampus, driving dopamine activity through projections to the striatum. The extent to which this model applies to the onset of psychosis in clinical subjects is unclea...

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Autores principales:	Paul Allen, Emily J. Hird, Natasza Orlov, Gemma Modinos, Matthijs Bossong, Mathilde Antoniades, Carly Sampson, Matilda Azis, Oliver Howes, James Stone, Jesus Perez, Matthew Broome, Antony A. Grace, Philip McGuire
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/8f67679a12be4d6f8abeb8495cd43e50
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spelling	oai:doaj.org-article:8f67679a12be4d6f8abeb8495cd43e502021-11-14T12:11:30ZAdverse clinical outcomes in people at clinical high-risk for psychosis related to altered interactions between hippocampal activity and glutamatergic function10.1038/s41398-021-01705-z2158-3188https://doaj.org/article/8f67679a12be4d6f8abeb8495cd43e502021-11-01T00:00:00Zhttps://doi.org/10.1038/s41398-021-01705-zhttps://doaj.org/toc/2158-3188Abstract Preclinical rodent models suggest that psychosis involves alterations in the activity and glutamatergic function in the hippocampus, driving dopamine activity through projections to the striatum. The extent to which this model applies to the onset of psychosis in clinical subjects is unclear. We assessed whether interactions between hippocampal glutamatergic function and activity/striatal connectivity are associated with adverse clinical outcomes in people at clinical high-risk (CHR) for psychosis. We measured functional Magnetic Resonance Imaging of hippocampal activation/connectivity, and 1H-Magnetic Resonance Spectroscopy of hippocampal glutamatergic metabolites in 75 CHR participants and 31 healthy volunteers. At follow-up, 12 CHR participants had transitioned to psychosis and 63 had not. Within the clinical high-risk cohort, at follow-up, 35 and 17 participants had a poor or a good functional outcome, respectively. The onset of psychosis (p peakFWE = 0.003, t = 4.4, z = 4.19) and a poor functional outcome (p peakFWE < 0.001, t = 5.52, z = 4.81 and p peakFWE < 0.001, t = 5.25, z = 4.62) were associated with a negative correlation between the hippocampal activation and hippocampal Glx concentration at baseline. In addition, there was a negative association between hippocampal Glx concentration and hippocampo-striatal connectivity (p peakFWE = 0.016, t = 3.73, z = 3.39, p peakFWE = 0.014, t = 3.78, z = 3.42, p peakFWE = 0.011, t = 4.45, z = 3.91, p peakFWE = 0.003, t = 4.92, z = 4.23) in the total CHR sample, not seen in healthy volunteers. As predicted by preclinical models, adverse clinical outcomes in people at risk for psychosis are associated with altered interactions between hippocampal activity and glutamatergic function.Paul AllenEmily J. HirdNatasza OrlovGemma ModinosMatthijs BossongMathilde AntoniadesCarly SampsonMatilda AzisOliver HowesJames StoneJesus PerezMatthew BroomeAntony A. GracePhilip McGuireNature Publishing GrouparticleNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENTranslational Psychiatry, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Paul Allen Emily J. Hird Natasza Orlov Gemma Modinos Matthijs Bossong Mathilde Antoniades Carly Sampson Matilda Azis Oliver Howes James Stone Jesus Perez Matthew Broome Antony A. Grace Philip McGuire Adverse clinical outcomes in people at clinical high-risk for psychosis related to altered interactions between hippocampal activity and glutamatergic function
description	Abstract Preclinical rodent models suggest that psychosis involves alterations in the activity and glutamatergic function in the hippocampus, driving dopamine activity through projections to the striatum. The extent to which this model applies to the onset of psychosis in clinical subjects is unclear. We assessed whether interactions between hippocampal glutamatergic function and activity/striatal connectivity are associated with adverse clinical outcomes in people at clinical high-risk (CHR) for psychosis. We measured functional Magnetic Resonance Imaging of hippocampal activation/connectivity, and 1H-Magnetic Resonance Spectroscopy of hippocampal glutamatergic metabolites in 75 CHR participants and 31 healthy volunteers. At follow-up, 12 CHR participants had transitioned to psychosis and 63 had not. Within the clinical high-risk cohort, at follow-up, 35 and 17 participants had a poor or a good functional outcome, respectively. The onset of psychosis (p peakFWE = 0.003, t = 4.4, z = 4.19) and a poor functional outcome (p peakFWE < 0.001, t = 5.52, z = 4.81 and p peakFWE < 0.001, t = 5.25, z = 4.62) were associated with a negative correlation between the hippocampal activation and hippocampal Glx concentration at baseline. In addition, there was a negative association between hippocampal Glx concentration and hippocampo-striatal connectivity (p peakFWE = 0.016, t = 3.73, z = 3.39, p peakFWE = 0.014, t = 3.78, z = 3.42, p peakFWE = 0.011, t = 4.45, z = 3.91, p peakFWE = 0.003, t = 4.92, z = 4.23) in the total CHR sample, not seen in healthy volunteers. As predicted by preclinical models, adverse clinical outcomes in people at risk for psychosis are associated with altered interactions between hippocampal activity and glutamatergic function.
format	article
author	Paul Allen Emily J. Hird Natasza Orlov Gemma Modinos Matthijs Bossong Mathilde Antoniades Carly Sampson Matilda Azis Oliver Howes James Stone Jesus Perez Matthew Broome Antony A. Grace Philip McGuire
author_facet	Paul Allen Emily J. Hird Natasza Orlov Gemma Modinos Matthijs Bossong Mathilde Antoniades Carly Sampson Matilda Azis Oliver Howes James Stone Jesus Perez Matthew Broome Antony A. Grace Philip McGuire
author_sort	Paul Allen
title	Adverse clinical outcomes in people at clinical high-risk for psychosis related to altered interactions between hippocampal activity and glutamatergic function
title_short	Adverse clinical outcomes in people at clinical high-risk for psychosis related to altered interactions between hippocampal activity and glutamatergic function
title_full	Adverse clinical outcomes in people at clinical high-risk for psychosis related to altered interactions between hippocampal activity and glutamatergic function
title_fullStr	Adverse clinical outcomes in people at clinical high-risk for psychosis related to altered interactions between hippocampal activity and glutamatergic function
title_full_unstemmed	Adverse clinical outcomes in people at clinical high-risk for psychosis related to altered interactions between hippocampal activity and glutamatergic function
title_sort	adverse clinical outcomes in people at clinical high-risk for psychosis related to altered interactions between hippocampal activity and glutamatergic function
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/8f67679a12be4d6f8abeb8495cd43e50
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Adverse clinical outcomes in people at clinical high-risk for psychosis related to altered interactions between hippocampal activity and glutamatergic function

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