TY - JOUR
T1 - Microglial activity in people at ultra high risk of psychosis and in schizophrenia
T2 - An [11C]PBR28 PET brain imaging study
AU - Bloomfield, Peter S.
AU - Selvaraj, Sudhakar
AU - Veronese, Mattia
AU - Rizzo, Gaia
AU - Bertoldo, Alessandra
AU - Owen, David R.
AU - Bloomfield, Michael A.P.
AU - Bonoldi, Ilaria
AU - Kalk, Nicola
AU - Turkheimer, Federico
AU - McGuire, Philip
AU - De Paola, Vincenzo
AU - Howes, Oliver D.
N1 - Funding Information:
Supported by a Medical Research Council (United Kingdom) grant to Dr. Howes (grant number MC-A656-5QD30) and a Maudsley Charity grant (grant number 666) to Dr. Howes, as well as the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King''s College London. The authors thank all the clinical imaging staff at Imanova for their assistance with this study, with particular thanks to QiGuo for her initial input and assistance with positron emission tomography methodology. The views expressed are those of the authors and do not necessarily represent those of the NHS, the NIHR, or the Department of Health. Mr. Bloomfield has conducted research funded by the Medical Research Council (United Kingdom), the National Institute of Health Research (United Kingdom), and the British Medical Association. Dr. Kalk received funding for a Ph.D. degree by a Wellcome Trust GlaxoSmithKline fellowship, and she has received grant support from GlaxoSmithKline to attend educational events and conferences. Dr. Howes has received investigator-initiated research funding fromand/or participated in advisory/speaker meetings organized by AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, Lundbeck, Lyden-Delta, Otsuka, Servier, and Roche. All other authors report no financial relationships with commercial interests.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - Objective: The purpose of this study was to determine whether microglial activity, measured using translocatorprotein positron emission tomography (PET) imaging, is increased in unmedicated persons presenting with subclinical symptoms indicating that they are at ultra high risk of psychosis and to determine whether microglial activity is elevated in schizophrenia after controlling for a translocatorspecific genetic polymorphism. Method: The authors used the second-generation radioligand [11C]PBR28 and PET to image microglial activity in the brains of participants at ultra high risk for psychosis. Participants were recruited from early intervention centers. The authors also imaged a cohort of patients with schizophrenia and matched healthy subjects for comparison. In total, 56 individuals completed the study. At screening, participants were genotyped to account for the rs6971 polymorphism in the gene encoding the 18Kd translocator protein. The main outcome measure was total gray matter [11C]PBR28 binding ratio, representing microglial activity. Results: [11C]PBR28 binding ratio in gray matter was elevated in ultra-high-risk participants compared with matched comparisonsubjects (Cohen'sd.1.2) and was positively cor related with symptom severity (r=0.730). Patients with schizophrenia also demonstrated elevated microglial activity relative to matched comparison subjects (Cohen's d.1.7). Conclusions: Microglial activity is elevated in patients with schizophrenia and in persons with subclinical symptomswho are at ultra high risk of psychosis and is related to at-risk symptom severity. These findings suggest that neuroinflammation is linked to the risk of psychosis and related disorders, as well as the expression of subclinical symptoms.
AB - Objective: The purpose of this study was to determine whether microglial activity, measured using translocatorprotein positron emission tomography (PET) imaging, is increased in unmedicated persons presenting with subclinical symptoms indicating that they are at ultra high risk of psychosis and to determine whether microglial activity is elevated in schizophrenia after controlling for a translocatorspecific genetic polymorphism. Method: The authors used the second-generation radioligand [11C]PBR28 and PET to image microglial activity in the brains of participants at ultra high risk for psychosis. Participants were recruited from early intervention centers. The authors also imaged a cohort of patients with schizophrenia and matched healthy subjects for comparison. In total, 56 individuals completed the study. At screening, participants were genotyped to account for the rs6971 polymorphism in the gene encoding the 18Kd translocator protein. The main outcome measure was total gray matter [11C]PBR28 binding ratio, representing microglial activity. Results: [11C]PBR28 binding ratio in gray matter was elevated in ultra-high-risk participants compared with matched comparisonsubjects (Cohen'sd.1.2) and was positively cor related with symptom severity (r=0.730). Patients with schizophrenia also demonstrated elevated microglial activity relative to matched comparison subjects (Cohen's d.1.7). Conclusions: Microglial activity is elevated in patients with schizophrenia and in persons with subclinical symptomswho are at ultra high risk of psychosis and is related to at-risk symptom severity. These findings suggest that neuroinflammation is linked to the risk of psychosis and related disorders, as well as the expression of subclinical symptoms.
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U2 - 10.1176/appi.ajp.2015.14101358
DO - 10.1176/appi.ajp.2015.14101358
M3 - Article
C2 - 26472628
AN - SCOPUS:84954204064
VL - 173
SP - 44
EP - 52
JO - American Journal of Psychiatry
JF - American Journal of Psychiatry
SN - 0002-953X
IS - 1
ER -