Imperial College London
Alternate

Professor David Nutt DM, FRCP, FRCPsych, FSB, FMedSci

Faculty of Medicine, Department of Brain Sciences

The Edmond J Safra Chair in Neuropsychopharmacology
 
 
 
//

Contact

 

d.nutt

 
 
//

Location

 

Burlington Danes BuildingBurlington DanesHammersmith Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Marques:2020:10.1038/s41380-020-0711-y,
author = {Marques, TR and Ashok, AH and Angelescu, I and Borgan, F and Myers, J and Lingford-Hughes, A and Nutt, DJ and Veronese, M and Turkheimer, FE and Howes, OD},
doi = {10.1038/s41380-020-0711-y},
journal = {Molecular Psychiatry},
pages = {2616--2625},
title = {GABA-A receptor differences in schizophrenia: a positron emission tomography study using [C-11]Ro154513},
url = {http://dx.doi.org/10.1038/s41380-020-0711-y},
volume = {26},
year = {2020}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - A loss of GABA signaling is a prevailing hypothesis for the pathogenesis of schizophrenia. Preclinical studies indicate that blockade of the α5 subtype of the GABA receptor (α5-GABAARs) leads to behavioral phenotypes associated with schizophrenia, and postmortem evidence indicates lower hippocampal α5-GABAARs protein and mRNA levels in schizophrenia. However, it is unclear if α5-GABAARs are altered in vivo or related to symptoms. We investigated α5-GABAARs availability in antipsychotic-free schizophrenia patients and antipsychotic-medicated schizophrenia patients using [11C]Ro15-4513 PET imaging in a cross-sectional, case–control study design. Thirty-one schizophrenia patients (n = 10 antipsychotic free) and twenty-nine matched healthy controls underwent a [11C]Ro15-4513 PET scan and MRI. The α5 subtype GABA-A receptor availability was indexed using [11C]Ro15-4513 PET imaging. Dynamic PET data were analyzed using the two-tissue compartment model with an arterial plasma input function and total volume of distribution (VT) as the outcome measure. Symptom severity was assessed using the PANSS scale. There was significantly lower [11C]Ro15-4513 VT in the hippocampus of antipsychotic-free patients, but not in medicated patients (p = 0.64), relative to healthy controls (p < 0.05; effect size = 1.4). There was also a significant positive correlation between [11C]Ro15-4513 VT and total PANSS score in antipsychotic-free patients (r = 0.72; p = 0.044). The results suggest that antipsychotic-free patients with schizophrenia have lower α5-GABAARs levels in the hippocampus, consistent with the hypothesis that GABA hypofunction underlies the pathophysiology of the disorder.
AU  - Marques,TR
AU  - Ashok,AH
AU  - Angelescu,I
AU  - Borgan,F
AU  - Myers,J
AU  - Lingford-Hughes,A
AU  - Nutt,DJ
AU  - Veronese,M
AU  - Turkheimer,FE
AU  - Howes,OD
DO  - 10.1038/s41380-020-0711-y
EP  - 2625
PY  - 2020///
SN  - 1359-4184
SP  - 2616
TI  - GABA-A receptor differences in schizophrenia: a positron emission tomography study using [C-11]Ro154513
T2  - Molecular Psychiatry
UR  - http://dx.doi.org/10.1038/s41380-020-0711-y
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000526337600001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.nature.com/articles/s41380-020-0711-y
UR  - http://hdl.handle.net/10044/1/80455
VL  - 26
ER  -
Download