title: In vivo imaging of brain microglial activity in antipsychotic-free and medicated schizophrenia: a [11C](R)-PK11195 positron emission tomography study.
abstract: Positron emission tomography (PET) imaging of the 18 kDa translocator protein (TSPO) has been used to investigate whether microglial activation, an indication of neuroinflammation, is evident in the brain of adults with schizophrenia. Interpretation of these studies is confounded by potential modulatory effects of antipsychotic medication on microglial activity. In the first such study in antipsychotic-free schizophrenia, we have used [11C](R)-PK11195 PET to compare TSPO availability in a predominantly antipsychotic-naive group of moderate-to-severely symptomatic unmedicated patients (n=8), similarly symptomatic medicated patients with schizophrenia taking risperidone or paliperidone by regular intramuscular injection (n=8), and healthy comparison subjects (n=16). We found no evidence for increased TSPO availability in antipsychotic-free patients compared with healthy controls (mean difference 4%, P=0.981). However, TSPO availability was significantly elevated in medicated patients (mean increase 88%, P=0.032) across prefrontal (dorsolateral, ventrolateral, orbital), anterior cingulate and parietal cortical regions. In the patients, TSPO availability was also strongly correlated with negative symptoms measured using the Positive and Negative Syndrome Scale across all the brain regions investigated (r=0.651-0.741). We conclude that the pathophysiology of schizophrenia is not associated with microglial activation in the 2-6 year period following diagnosis. The elevation in the medicated patients may be a direct effect of the antipsychotic, although this study cannot exclude treatment resistance and/or longer illness duration as potential explanations. It also remains to be determined whether it is present only in a subset of patients, represents a pro- or anti-inflammatory state, its association with primary negative symptoms, and whether there are significant differences between antipsychotics.
authors.affiliation: Wolfson Molecular Imaging Centre, Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
authors.forename: S E
authors.initials: SE
authors.lastname: Holmes
authors.affiliation: Wolfson Molecular Imaging Centre, Division of Informatics, Imaging & Data Sciences, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
authors.forename: R
authors.initials: R
authors.lastname: Hinz
authors.affiliation: Division of Psychology & Mental Health, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
authors.forename: R J
authors.initials: RJ
authors.lastname: Drake
authors.affiliation: Wolfson Molecular Imaging Centre, Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
authors.forename: C J
authors.initials: CJ
authors.lastname: Gregory
authors.affiliation: Wolfson Molecular Imaging Centre, Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
authors.forename: S
authors.initials: S
authors.lastname: Conen
authors.affiliation: Wolfson Molecular Imaging Centre, Division of Informatics, Imaging & Data Sciences, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
authors.forename: J C
authors.initials: JC
authors.lastname: Matthews
authors.affiliation: Wolfson Molecular Imaging Centre, Division of Informatics, Imaging & Data Sciences, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
authors.forename: J M
authors.initials: JM
authors.lastname: Anton-Rodriguez
authors.affiliation: Wolfson Molecular Imaging Centre, Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
authors.forename: A
authors.initials: A
authors.lastname: Gerhard
authors.affiliation: Wolfson Molecular Imaging Centre, Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
authors.forename: P S
authors.initials: PS
authors.lastname: Talbot
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects; D005260:Female; D006179:Gyrus Cinguli / Q000503:physiopathology; D006801:Humans; D007546:Isoquinolines; D008297:Male; D017628:Microglia; D000068882:Paliperidone Palmitate; D049268:Positron-Emission Tomography / Q000379:methods; D018079:Receptors, GABA / Q000502:physiology*; D018967:Risperidone; D012559:Schizophrenia / Q000000981:diagnostic imaging* / Q000188:drug therapy
chemical_list: D014150:Antipsychotic Agents; D007546:Isoquinolines; D018079:Receptors, GABA; C499229:TSPO protein, human; D018967:Risperidone; D000068882:Paliperidone Palmitate; C037850:PK 11195