Livia De Picker1, Julie Ottoy2, Jeroen Verhaeghe2, Steven Deleye2, Leonie Wyffels3, Erik Fransen4, Lauren Kosten2, Bernard Sabbe5, Violette Coppens5, Maarten Timmers6, Peter de Boer7, Luc Van Nueten7, Ken Op De Beeck8, Herbert Oberacher9, Filip Vanhoenacker10, Sarah Ceyssens3, Sigrid Stroobants3, Steven Staelens2, Manuel Morrens5. 1. Collaborative Antwerp Psychiatric Research Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium; University Psychiatric Hospital Antwerp, Campus Duffel, Duffel, Belgium. Electronic address: livia.depicker@uantwerp.be. 2. Molecular Imaging Center Antwerp, University of Antwerp, Antwerp, Belgium. 3. Department of Nuclear Medicine, Antwerp University Hospital, Edegem, Belgium. 4. StatUa Center for Statistics, University of Antwerp, Belgium. 5. Collaborative Antwerp Psychiatric Research Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium; University Psychiatric Hospital Antwerp, Campus Duffel, Duffel, Belgium. 6. Janssen Research and Development, Janssen Pharmaceutica N.V., Beerse, Belgium; Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerp, Belgium. 7. Janssen Research and Development, Janssen Pharmaceutica N.V., Beerse, Belgium. 8. Medical Genetics Research Group, University of Antwerp, Antwerp, Belgium. 9. Institute of Legal Medicine and Core Facility Metabolomics, Medical University of Innsbruck, Innsbruck, Austria. 10. Department of Radiology, Sint-Maarten General Hospital, Mechelen, Belgium; Faculty of Medicine and Health Sciences, Universities of Antwerp and Ghent, Belgium.
Abstract
OBJECTIVE: To determine whether state-associated changes in microglial activity, measured with translocator-protein positron emission tomography (TSPO PET), can be identified in psychosis patients through longitudinal evaluation of their regional tracer uptake over the clinical course from acute psychosis to post-treatment follow-up, and comparison to healthy controls. We also evaluated the relation between tracer uptake, clinical symptoms and peripheral immunological markers. METHOD: Second-generation radioligand [18F]-PBR111 TSPO PET-CT was used for longitudinal dynamic imaging in 14 male psychosis patients and 17 male age-matched healthy control subjects. Patients were first scanned during an acute psychotic episode followed by a second scan after treatment. Prior genotyping of subjects for the rs6917 polymorphism distinguished high- and mixed-affinity binders. The main outcome was regional volume of distribution (VT), representing TSPO binding. Plasma concentrations of CRP, cytokines and kynurenines were measured at each timepoint. RESULTS: We found a significant three-way interaction between time of scan, age and cohort (cortical grey matter F6.50, p.020). Age-dependent differences in VT existed between cohorts during the psychotic state, but not at follow-up. Patients' relative change in VT over time correlated with age (cortical grey matter Pearson's r.574). PANSS positive subscale scores correlated with regional VT during psychosis (cortical grey matter r.767). Plasma CRP and quinolinic acid were independently associated with lower VT. CONCLUSIONS: We identified a differential age-dependent pattern of TSPO binding from psychosis to follow-up in our cohort of male psychosis patients. We recommend future TSPO PET studies in psychosis patients to differentiate between clinical states and consider potential age-related effects.
OBJECTIVE: To determine whether state-associated changes in microglial activity, measured with translocator-protein positron emission tomography (TSPO PET), can be identified in psychosispatients through longitudinal evaluation of their regional tracer uptake over the clinical course from acute psychosis to post-treatment follow-up, and comparison to healthy controls. We also evaluated the relation between tracer uptake, clinical symptoms and peripheral immunological markers. METHOD: Second-generation radioligand [18F]-PBR111 TSPO PET-CT was used for longitudinal dynamic imaging in 14 male psychosispatients and 17 male age-matched healthy control subjects. Patients were first scanned during an acute psychotic episode followed by a second scan after treatment. Prior genotyping of subjects for the rs6917 polymorphism distinguished high- and mixed-affinity binders. The main outcome was regional volume of distribution (VT), representing TSPO binding. Plasma concentrations of CRP, cytokines and kynurenines were measured at each timepoint. RESULTS: We found a significant three-way interaction between time of scan, age and cohort (cortical grey matter F6.50, p.020). Age-dependent differences in VT existed between cohorts during the psychotic state, but not at follow-up. Patients' relative change in VT over time correlated with age (cortical grey matter Pearson's r.574). PANSS positive subscale scores correlated with regional VT during psychosis (cortical grey matter r.767). Plasma CRP and quinolinic acid were independently associated with lower VT. CONCLUSIONS: We identified a differential age-dependent pattern of TSPO binding from psychosis to follow-up in our cohort of male psychosispatients. We recommend future TSPO PET studies in psychosispatients to differentiate between clinical states and consider potential age-related effects.
Authors: Pontus Plavén-Sigray; Granville J Matheson; Jennifer M Coughlin; Sina Hafizi; Heikki Laurikainen; Julie Ottoy; Livia De Picker; Pablo Rusjan; Jarmo Hietala; Oliver D Howes; Romina Mizrahi; Manuel Morrens; Martin G Pomper; Simon Cervenka Journal: Biol Psychiatry Date: 2020-07-15 Impact factor: 13.382
Authors: Livia De Picker; Erik Fransen; Violette Coppens; Maarten Timmers; Peter de Boer; Herbert Oberacher; Dietmar Fuchs; Robert Verkerk; Bernard Sabbe; Manuel Morrens Journal: Front Immunol Date: 2020-01-17 Impact factor: 7.561
Authors: Natalya A Uranova; Olga V Vikhreva; Valentina I Rakhmanova; Diana D Orlovskaya Journal: Front Psychiatry Date: 2020-03-26 Impact factor: 4.157