Altered Medial Temporal Activation Related to Local Glutamate Levels in Subjects with Prodromal Signs of Psychosis

Isabel Valli; James Stone; Andrea Mechelli; Sagnik Bhattacharyya; Marie Raffin; Paul Allen; Paolo Fusar-Poli; David Lythgoe; Ruth O'Gorman; Marc Seal; Philip McGuire

doi:10.1016/j.biopsych.2010.08.033

Altered Medial Temporal Activation Related to Local Glutamate Levels in Subjects with Prodromal Signs of Psychosis

Isabel Valli, James Stone, Andrea Mechelli, Sagnik Bhattacharyya, Marie Raffin, Paul Allen, Paolo Fusar-Poli, David Lythgoe, Ruth O'Gorman, Marc Seal, Philip McGuire

Research output: Contribution to journal › Article

Abstract

Background: Both medial temporal cortical dysfunction and perturbed glutamatergic neurotransmission are regarded as fundamental pathophysiological features of psychosis. However, although animal models of psychosis suggest that these two abnormalities are interrelated, their relationship in humans has yet to be investigated.Methods: We used a combination of functional magnetic resonance imaging and magnetic resonance spectroscopy to investigate the relationship between medial temporal activation during an episodic memory task and local glutamate levels in 22 individuals with an at-risk mental state for psychosis and 14 healthy volunteers.Results: We observed a significant between-group difference in the coupling of medial temporal activation with local glutamate levels. In control subjects, medial temporal activation during episodic encoding was positively associated with medial temporal glutamate. However, in the clinical population, medial temporal activation was reduced, and the relationship with glutamate was absent.Conclusions: In individuals at high risk of psychosis, medial temporal dysfunction seemed related to a loss of the normal relationship with local glutamate levels. This study provides the first evidence that links medial temporal dysfunction with the central glutamate system in humans and is consistent with evidence that drugs that modulate glutamatergic transmission might be useful in the treatment of psychosis.

Original language	English
Pages (from-to)	97-99
Journal	Biological Psychiatry
Volume	69
Issue number	1
DOIs	https://doi.org/10.1016/j.biopsych.2010.08.033
Publication status	Published - 2011

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10.1016/j.biopsych.2010.08.033

http://dx.doi.org/10.1016/j.biopsych.2010.08.033

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@article{f47ea7a1f5014ba9bb63cf36a801d926,

title = "Altered Medial Temporal Activation Related to Local Glutamate Levels in Subjects with Prodromal Signs of Psychosis",

abstract = "Background: Both medial temporal cortical dysfunction and perturbed glutamatergic neurotransmission are regarded as fundamental pathophysiological features of psychosis. However, although animal models of psychosis suggest that these two abnormalities are interrelated, their relationship in humans has yet to be investigated.Methods: We used a combination of functional magnetic resonance imaging and magnetic resonance spectroscopy to investigate the relationship between medial temporal activation during an episodic memory task and local glutamate levels in 22 individuals with an at-risk mental state for psychosis and 14 healthy volunteers.Results: We observed a significant between-group difference in the coupling of medial temporal activation with local glutamate levels. In control subjects, medial temporal activation during episodic encoding was positively associated with medial temporal glutamate. However, in the clinical population, medial temporal activation was reduced, and the relationship with glutamate was absent.Conclusions: In individuals at high risk of psychosis, medial temporal dysfunction seemed related to a loss of the normal relationship with local glutamate levels. This study provides the first evidence that links medial temporal dysfunction with the central glutamate system in humans and is consistent with evidence that drugs that modulate glutamatergic transmission might be useful in the treatment of psychosis.",

author = "Isabel Valli and James Stone and Andrea Mechelli and Sagnik Bhattacharyya and Marie Raffin and Paul Allen and Paolo Fusar-Poli and David Lythgoe and Ruth O'Gorman and Marc Seal and Philip McGuire",

year = "2011",

doi = "10.1016/j.biopsych.2010.08.033",

language = "English",

volume = "69",

pages = "97--99",

journal = "Biological Psychiatry",

issn = "0006-3223",

publisher = "Elsevier",

number = "1",

}

TY - JOUR

T1 - Altered Medial Temporal Activation Related to Local Glutamate Levels in Subjects with Prodromal Signs of Psychosis

AU - Valli, Isabel

AU - Stone, James

AU - Mechelli, Andrea

AU - Bhattacharyya, Sagnik

AU - Raffin, Marie

AU - Allen, Paul

AU - Fusar-Poli, Paolo

AU - Lythgoe, David

AU - O'Gorman, Ruth

AU - Seal, Marc

AU - McGuire, Philip

PY - 2011

Y1 - 2011

N2 - Background: Both medial temporal cortical dysfunction and perturbed glutamatergic neurotransmission are regarded as fundamental pathophysiological features of psychosis. However, although animal models of psychosis suggest that these two abnormalities are interrelated, their relationship in humans has yet to be investigated.Methods: We used a combination of functional magnetic resonance imaging and magnetic resonance spectroscopy to investigate the relationship between medial temporal activation during an episodic memory task and local glutamate levels in 22 individuals with an at-risk mental state for psychosis and 14 healthy volunteers.Results: We observed a significant between-group difference in the coupling of medial temporal activation with local glutamate levels. In control subjects, medial temporal activation during episodic encoding was positively associated with medial temporal glutamate. However, in the clinical population, medial temporal activation was reduced, and the relationship with glutamate was absent.Conclusions: In individuals at high risk of psychosis, medial temporal dysfunction seemed related to a loss of the normal relationship with local glutamate levels. This study provides the first evidence that links medial temporal dysfunction with the central glutamate system in humans and is consistent with evidence that drugs that modulate glutamatergic transmission might be useful in the treatment of psychosis.

AB - Background: Both medial temporal cortical dysfunction and perturbed glutamatergic neurotransmission are regarded as fundamental pathophysiological features of psychosis. However, although animal models of psychosis suggest that these two abnormalities are interrelated, their relationship in humans has yet to be investigated.Methods: We used a combination of functional magnetic resonance imaging and magnetic resonance spectroscopy to investigate the relationship between medial temporal activation during an episodic memory task and local glutamate levels in 22 individuals with an at-risk mental state for psychosis and 14 healthy volunteers.Results: We observed a significant between-group difference in the coupling of medial temporal activation with local glutamate levels. In control subjects, medial temporal activation during episodic encoding was positively associated with medial temporal glutamate. However, in the clinical population, medial temporal activation was reduced, and the relationship with glutamate was absent.Conclusions: In individuals at high risk of psychosis, medial temporal dysfunction seemed related to a loss of the normal relationship with local glutamate levels. This study provides the first evidence that links medial temporal dysfunction with the central glutamate system in humans and is consistent with evidence that drugs that modulate glutamatergic transmission might be useful in the treatment of psychosis.

U2 - 10.1016/j.biopsych.2010.08.033

DO - 10.1016/j.biopsych.2010.08.033

M3 - Article

SN - 0006-3223

VL - 69

SP - 97

EP - 99

JO - Biological Psychiatry

JF - Biological Psychiatry

IS - 1

ER -