title: Lower levels of the glial cell marker TSPO in drug-naive first-episode psychosis patients as measured using PET and [11C]PBR28.
abstract: Several lines of evidence are indicative of a role for immune activation in the pathophysiology of schizophrenia. Nevertheless, studies using positron emission tomography (PET) and radioligands for the translocator protein (TSPO), a marker for glial activation, have yielded inconsistent results. Whereas early studies using a radioligand with low signal-to-noise in small samples showed increases in patients, more recent studies with improved methodology have shown no differences or trend-level decreases. Importantly, all patients investigated thus far have been on antipsychotic medication, and as these compounds may dampen immune cell activity, this factor limits the conclusions that can be drawn. Here, we examined 16 drug-naive, first-episode psychosis patients and 16 healthy controls using PET and the TSPO radioligand [11C]PBR28. Gray matter (GM) volume of distribution (VT) derived from a two-tissue compartmental analysis with arterial input function was the main outcome measure. Statistical analyses were performed controlling for both TSPO genotype, which is known to affect [11C]PBR28 binding, and gender. There was a significant reduction of [11C]PBR28 VTin patients compared with healthy controls in GM as well as in secondary regions of interest. No correlation was observed between GM VTand clinical or cognitive measures after correction for multiple comparisons. The observed decrease in TSPO binding suggests reduced numbers or altered function of immune cells in brain in early-stage schizophrenia.
authors.affiliation: Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Collste
authors.affiliation: Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Plavén-Sigray
authors.affiliation: Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Fatouros-Bergman
authors.affiliation: Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Victorsson
authors.affiliation: Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.|Molecular Imaging and Neuropathology Division, Department of Psychiatry, Columbia University, New York, NY, USA.
authors.forename: M
authors.initials: M
authors.lastname: Schain
authors.affiliation: Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Forsberg
authors.affiliation: Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
authors.forename: N
authors.initials: N
authors.lastname: Amini
authors.affiliation: Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Aeinehband
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Erhardt
authors.affiliation: Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Halldin
authors.affiliation: Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Flyckt
authors.affiliation: Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.|Personalised Healthcare and Biomarkers, AstraZeneca PET Science Centre, Karolinska Institutet, Stockholm, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Farde
authors.affiliation: Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.|Department of Psychiatry, University of Cambridge, Cambridge, UK.
authors.forename: S
authors.initials: S
authors.lastname: Cervenka
mesh_terms: D000081:Acetamides; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D002250:Carbon Radioisotopes; D016022:Case-Control Studies; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000382:microbiology; D006801:Humans; D008297:Male; D017628:Microglia / Q000378:metabolism; D009457:Neuroglia / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology; D049268:Positron-Emission Tomography / Q000379:methods; D011618:Psychotic Disorders / Q000000981:diagnostic imaging*; D011725:Pyridines; D011869:Radioligand Assay; D019275:Radiopharmaceuticals; D018079:Receptors, GABA / Q000032:analysis* / Q000378:metabolism; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology
chemical_list: D000081:Acetamides; D015415:Biomarkers; D002250:Carbon Radioisotopes; C526798:N-(2-methoxybenzyl)-N-(4-phenoxypyridin-3-yl)acetamide; D011725:Pyridines; D019275:Radiopharmaceuticals; D018079:Receptors, GABA; C499229:TSPO protein, human