Cortical GABA In Subjects At Ultra-High Risk Of Psychosis: Relationship To Negative Prodromal Symptoms

Gemma Modinos; Fatma Simsek; Jamie Horder; Matthijs Geert Bossong; Ilaria Bonoldi; Matilda Azis; Jesus Perez; Matthew Broome; David John Lythgoe; James Michael Stone; Oliver David Howes; Declan G Murphy; Anthony A Grace; Paul Allen; Philip McGuire

doi:10.1093/ijnp/pyx076

Cortical GABA In Subjects At Ultra-High Risk Of Psychosis: Relationship To Negative Prodromal Symptoms

Gemma Modinos, Fatma Simsek, Jamie Horder, Matthijs Geert Bossong, Ilaria Bonoldi, Matilda Azis, Jesus Perez, Matthew Broome, David John Lythgoe, James Michael Stone, Oliver David Howes, Declan G Murphy, Anthony A Grace, Paul Allen, Philip McGuire

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29 Citations (Scopus)

Abstract

Background: Whilst robust preclinical and postmortem evidence suggests that altered GABAergic function is central to the development of psychosis, little is known about whether it is altered in subjects at ultra-high risk of psychosis, or its relationship to prodromal symptoms.
Methods: Twenty-one anti-psychotic naïve UHR individuals and 20 healthy volunteers underwent proton magnetic resonance imaging at 3T. GABA levels were obtained from the medial prefrontal cortex (MPFC) using MEGA-PRESS, and expressed as peak-area ratios relative to the synchronously-acquired creatine signal. GABA levels were then related to severity of positive and negative symptoms as measured with the Community Assessment of At-Risk Mental States.
Results: Whilst we found no significant difference in GABA levels between UHR subjects and healthy controls (P = .130), in UHR individuals MPFC GABA levels were negatively correlated with the severity of negative symptoms (P = .013).
Conclusion: These findings suggest that GABAergic neurotransmission may be involved in the neurobiology of negative symptoms in the UHR state.

Original language	English
Journal	International Journal of Neuropsychopharmacology
DOIs	https://doi.org/10.1093/ijnp/pyx076
Publication status	Published - 19 Aug 2017

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https://academic.oup.com/ijnp/article/doi/10.1093/ijnp/pyx076/4085585/Cortical-GABA-In-Subjects-At-UltraHigh-Risk-Of?guestAccessKey=811fab27-6257-4ec6-adb2-9e641b155c1eLicence: CC BY

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Modinos, G., Simsek, F., Horder, J., Bossong, M. G., Bonoldi, I., Azis, M., Perez, J., Broome, M., Lythgoe, D. J., Stone, J. M., Howes, O. D., Murphy, D. G., Grace, A. A., Allen, P., & McGuire, P. (2017). Cortical GABA In Subjects At Ultra-High Risk Of Psychosis: Relationship To Negative Prodromal Symptoms. International Journal of Neuropsychopharmacology . https://doi.org/10.1093/ijnp/pyx076

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title = "Cortical GABA In Subjects At Ultra-High Risk Of Psychosis: Relationship To Negative Prodromal Symptoms",

abstract = "Background: Whilst robust preclinical and postmortem evidence suggests that altered GABAergic function is central to the development of psychosis, little is known about whether it is altered in subjects at ultra-high risk of psychosis, or its relationship to prodromal symptoms.Methods: Twenty-one anti-psychotic na{\"i}ve UHR individuals and 20 healthy volunteers underwent proton magnetic resonance imaging at 3T. GABA levels were obtained from the medial prefrontal cortex (MPFC) using MEGA-PRESS, and expressed as peak-area ratios relative to the synchronously-acquired creatine signal. GABA levels were then related to severity of positive and negative symptoms as measured with the Community Assessment of At-Risk Mental States. Results: Whilst we found no significant difference in GABA levels between UHR subjects and healthy controls (P = .130), in UHR individuals MPFC GABA levels were negatively correlated with the severity of negative symptoms (P = .013).Conclusion: These findings suggest that GABAergic neurotransmission may be involved in the neurobiology of negative symptoms in the UHR state.",

author = "Gemma Modinos and Fatma Simsek and Jamie Horder and Bossong, {Matthijs Geert} and Ilaria Bonoldi and Matilda Azis and Jesus Perez and Matthew Broome and Lythgoe, {David John} and Stone, {James Michael} and Howes, {Oliver David} and Murphy, {Declan G} and Grace, {Anthony A} and Paul Allen and Philip McGuire",

year = "2017",

month = aug,

day = "19",

doi = "10.1093/ijnp/pyx076",

language = "English",

journal = "International Journal of Neuropsychopharmacology ",

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T1 - Cortical GABA In Subjects At Ultra-High Risk Of Psychosis

T2 - Relationship To Negative Prodromal Symptoms

AU - Modinos, Gemma

AU - Simsek, Fatma

AU - Horder, Jamie

AU - Bossong, Matthijs Geert

AU - Bonoldi, Ilaria

AU - Azis, Matilda

AU - Perez, Jesus

AU - Broome, Matthew

AU - Lythgoe, David John

AU - Stone, James Michael

AU - Howes, Oliver David

AU - Murphy, Declan G

AU - Grace, Anthony A

AU - Allen, Paul

AU - McGuire, Philip

PY - 2017/8/19

Y1 - 2017/8/19

N2 - Background: Whilst robust preclinical and postmortem evidence suggests that altered GABAergic function is central to the development of psychosis, little is known about whether it is altered in subjects at ultra-high risk of psychosis, or its relationship to prodromal symptoms.Methods: Twenty-one anti-psychotic naïve UHR individuals and 20 healthy volunteers underwent proton magnetic resonance imaging at 3T. GABA levels were obtained from the medial prefrontal cortex (MPFC) using MEGA-PRESS, and expressed as peak-area ratios relative to the synchronously-acquired creatine signal. GABA levels were then related to severity of positive and negative symptoms as measured with the Community Assessment of At-Risk Mental States. Results: Whilst we found no significant difference in GABA levels between UHR subjects and healthy controls (P = .130), in UHR individuals MPFC GABA levels were negatively correlated with the severity of negative symptoms (P = .013).Conclusion: These findings suggest that GABAergic neurotransmission may be involved in the neurobiology of negative symptoms in the UHR state.

AB - Background: Whilst robust preclinical and postmortem evidence suggests that altered GABAergic function is central to the development of psychosis, little is known about whether it is altered in subjects at ultra-high risk of psychosis, or its relationship to prodromal symptoms.Methods: Twenty-one anti-psychotic naïve UHR individuals and 20 healthy volunteers underwent proton magnetic resonance imaging at 3T. GABA levels were obtained from the medial prefrontal cortex (MPFC) using MEGA-PRESS, and expressed as peak-area ratios relative to the synchronously-acquired creatine signal. GABA levels were then related to severity of positive and negative symptoms as measured with the Community Assessment of At-Risk Mental States. Results: Whilst we found no significant difference in GABA levels between UHR subjects and healthy controls (P = .130), in UHR individuals MPFC GABA levels were negatively correlated with the severity of negative symptoms (P = .013).Conclusion: These findings suggest that GABAergic neurotransmission may be involved in the neurobiology of negative symptoms in the UHR state.

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DO - 10.1093/ijnp/pyx076

M3 - Article

SN - 1461-1457

JO - International Journal of Neuropsychopharmacology

JF - International Journal of Neuropsychopharmacology

ER -

Cortical GABA In Subjects At Ultra-High Risk Of Psychosis: Relationship To Negative Prodromal Symptoms

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