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

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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.

In: Neuropsychopharmacology, 30.01.2018.

Research output: Contribution to journalArticle

Harvard

Modinos, G, Şimşek, F, Azis, M, Bossong, M, Bonoldi, I, Samson, C, Quinn, B, Perez, J, Broome, MR, Zelaya, F, Lythgoe, DJ, Howes, OD, Stone, JM, Grace, AA, Allen, P & McGuire, P 2018, 'Prefrontal GABA levels, hippocampal resting perfusion and the risk of psychosis', Neuropsychopharmacology. https://doi.org/10.1038/s41386-017-0004-6

APA

Modinos, G., Şimşek, F., Azis, M., Bossong, M., Bonoldi, I., Samson, C., ... McGuire, P. (2018). Prefrontal GABA levels, hippocampal resting perfusion and the risk of psychosis. Neuropsychopharmacology. https://doi.org/10.1038/s41386-017-0004-6

Vancouver

Modinos G, Şimşek F, Azis M, Bossong M, Bonoldi I, Samson C et al. Prefrontal GABA levels, hippocampal resting perfusion and the risk of psychosis. Neuropsychopharmacology. 2018 Jan 30. https://doi.org/10.1038/s41386-017-0004-6

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. / Prefrontal GABA levels, hippocampal resting perfusion and the risk of psychosis. In: Neuropsychopharmacology. 2018.

Bibtex Download

@article{8cfa3dfd68b046cc850a2faa24c34486,
title = "Prefrontal GABA levels, hippocampal resting perfusion and the risk of psychosis",
abstract = "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 = .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 = .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.",
author = "Gemma Modinos and Fatma Şimşek and Matilda Azis and Matthijs Bossong and Ilaria Bonoldi and Carly Samson and Beverly Quinn and Jesus Perez and Broome, {Matthew R} and Fernando Zelaya and Lythgoe, {David J} and Howes, {Oliver D} and Stone, {James M} and Grace, {Anthony A} and Paul Allen and Philip McGuire",
year = "2018",
month = "1",
day = "30",
doi = "10.1038/s41386-017-0004-6",
language = "English",
journal = "Neuropsychopharmacology",
issn = "0893-133X",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Prefrontal GABA levels, hippocampal resting perfusion and the risk of psychosis

AU - Modinos, Gemma

AU - Şimşek, Fatma

AU - Azis, Matilda

AU - Bossong, Matthijs

AU - Bonoldi, Ilaria

AU - Samson, Carly

AU - Quinn, Beverly

AU - Perez, Jesus

AU - Broome, Matthew R

AU - Zelaya, Fernando

AU - Lythgoe, David J

AU - Howes, Oliver D

AU - Stone, James M

AU - Grace, Anthony A

AU - Allen, Paul

AU - McGuire, Philip

PY - 2018/1/30

Y1 - 2018/1/30

N2 - 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 = .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 = .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.

AB - 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 = .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 = .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.

UR - http://www.scopus.com/inward/record.url?scp=85041904055&partnerID=8YFLogxK

U2 - 10.1038/s41386-017-0004-6

DO - 10.1038/s41386-017-0004-6

M3 - Article

C2 - 29440719

JO - Neuropsychopharmacology

JF - Neuropsychopharmacology

SN - 0893-133X

ER -

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