PET imaging of putative microglial activation in individuals at ultra-high risk for psychosis, recently diagnosed and chronically ill with schizophrenia

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dc.contributor.authorDi Biase, M.
dc.contributor.authorZalesky, A.
dc.contributor.authorO'keefe, G.
dc.contributor.authorLaskaris, L.
dc.contributor.authorBaune, B.
dc.contributor.authorWeickert, C.
dc.contributor.authorOlver, J.
dc.contributor.authorMcGorry, P.
dc.contributor.authorAmminger, G.
dc.contributor.authorNelson, B.
dc.contributor.authorScott, A.
dc.contributor.authorHickie, I.
dc.contributor.authorBanati, R.
dc.contributor.authorTurkheimer, F.
dc.contributor.authorYaqub, M.
dc.contributor.authorEverall, I.
dc.contributor.authorPantelis, C.
dc.contributor.authorCropley, V.
dc.date.issued2017
dc.description.abstractWe examined putative microglial activation as a function of illness course in schizophrenia. Microglial activity was quantified using [11C](R)-(1-[2-chrorophynyl]-N-methyl-N-[1-methylpropyl]-3 isoquinoline carboxamide (11C-(R)-PK11195) positron emission tomography (PET) in: (i) 10 individuals at ultra-high risk (UHR) of psychosis; (ii) 18 patients recently diagnosed with schizophrenia; (iii) 15 patients chronically ill with schizophrenia; and, (iv) 27 age-matched healthy controls. Regional-binding potential (BPND) was calculated using the simplified reference-tissue model with four alternative reference inputs. The UHR, recent-onset and chronic patient groups were compared to age-matched healthy control groups to examine between-group BPND differences in 6 regions: dorsal frontal, orbital frontal, anterior cingulate, medial temporal, thalamus and insula. Correlation analysis tested for BPND associations with gray matter volume, peripheral cytokines and clinical variables. The null hypothesis of equality in BPND between patients (UHR, recent-onset and chronic) and respective healthy control groups (younger and older) was not rejected for any group comparison or region. Across all subjects, BPND was positively correlated to age in the thalamus (r=0.43, P=0.008, false discovery rate). No correlations with regional gray matter, peripheral cytokine levels or clinical symptoms were detected. We therefore found no evidence of microglial activation in groups of individuals at high risk, recently diagnosed or chronically ill with schizophrenia. While the possibility of 11C-(R)-PK11195-binding differences in certain patient subgroups remains, the patient cohorts in our study, who also displayed normal peripheral cytokine profiles, do not substantiate the assumption of microglial activation in schizophrenia as a regular and defining feature, as measured by 11C-(R)-PK11195 BPND.
dc.description.statementofresponsibilityM A Di Biase, A Zalesky, G O'keefe, L Laskaris, B T Baune, C S Weickert, J Olver, P D McGorry, G P Amminger, B Nelson, A M Scott, I Hickie, R Banati, F Turkheimer, M Yaqub, I P Everall, C Pantelis and V Cropley
dc.identifier.citationTranslational Psychiatry, 2017; 7(8):e1225-1-e1225-8
dc.identifier.doi10.1038/tp.2017.193
dc.identifier.issn2158-3188
dc.identifier.issn2158-3188
dc.identifier.orcidBaune, B. [0000-0001-6548-426X]
dc.identifier.urihttp://hdl.handle.net/2440/109235
dc.language.isoen
dc.publisherNature Publishing Group
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1065742
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/628386
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1105825
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1117079
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/628880
dc.rights© The Author(s) 2017. This work is licensed under a Creative Commons Attribution- NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if thematerial is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http:// creativecommons.org/licenses/by-nc-sa/4.0/.
dc.source.urihttps://doi.org/10.1038/tp.2017.193
dc.subjectBrain
dc.subjectMicroglia
dc.subjectHumans
dc.subjectCarbon Radioisotopes
dc.subjectIsoquinolines
dc.subjectReceptors, GABA
dc.subjectPositron-Emission Tomography
dc.subjectRisk Factors
dc.subjectPsychotic Disorders
dc.subjectSchizophrenia
dc.subjectAdolescent
dc.subjectAdult
dc.subjectFemale
dc.subjectMale
dc.subjectYoung Adult
dc.titlePET imaging of putative microglial activation in individuals at ultra-high risk for psychosis, recently diagnosed and chronically ill with schizophrenia
dc.typeJournal article
pubs.publication-statusPublished

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