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PET studies of the glial cell marker TSPO in psychosis patients - a meta-analysis using individual participant data

By Pontus Plavén-Sigray, Granville J. Matheson, Karin Collste, Abhishekh H Ashok, Jennifer M Coughlin, Oliver D Howes, Romina Mizrahi, Martin G Pomper, Pablo Rusjan, Mattia Veronese, Yuchuan Wang, Simon Cervenka

Posted 05 Dec 2017
bioRxiv DOI: 10.1101/228742 (published DOI: 10.1016/j.biopsych.2018.02.1171)

Background: Accumulating evidence suggests that the immune system may be an important target for new treatment approaches in schizophrenia. Positron emission tomography (PET) and radioligands binding to the translocator protein (TSPO), which is expressed in glial cells in brain including immune cells, represents a potential method for patient stratification and treatment monitoring. This study examined if patients with first episode psychosis and schizophrenia had altered TSPO levels as compared to healthy control subjects. Methods: PubMed was searched for studies comparing patients with psychosis to healthy controls using second-generation TSPO radioligands. The outcome measure was distribution volume (VT), an index of TSPO levels, in frontal cortex (FC), temporal cortex (TC) and hippocampus (HIP). Bayes factors (BF) were applied to examine the relative support for higher, lower or no-change of TSPO levels in patients as compared to healthy controls.Results: Five studies, with 75 patients with first-episode psychosis or schizophrenia and 77 healthy control subjects were included. BF showed strong support for lower patient VT relative to no-change (all BF>32) or relative to an increase (all BF>422) in all brain regions. From the posterior distributions, mean patient-control differences in standardized VT values were -0.48 for FC (95% credible interval (CredInt)=-0.88 to -0.09), -0.47 for TC (CredInt=-0.87 to -0.07) and -0.63 for HIP (CredInt=-1.00 to -0.25). Discussion: The observed reduction of TPSO compared to control subjects in patients may correspond to altered function or lower density of brain immune cells. Future studies should focus on investigating the underlying biological mechanisms and their relevance for treatment.

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