1. A Modest Increase in 11C-PK11195-Positron Emission Tomography TSPO Binding in Depression Is Not Associated With Serum C-Reactive Protein or Body Mass Index
- Author
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Julia J. Schubert, Mattia Veronese, Tim D. Fryer, Roido Manavaki, Manfred G. Kitzbichler, Maria A. Nettis, Valeria Mondelli, Carmine M. Pariante, Edward T. Bullmore, Federico E. Turkheimer, Dominika Wlazly, Amber Dickinson, Andy Foster, Clare Knight, Claire Leckey, Paul Morgan, Angharad Morgan, Caroline O'Hagan, Samuel Touchard, Shahid Khan, Phil Murphy, Christine Parker, Jai Patel, Jill Richardson, Paul Acton, Nigel Austin, Anindya Bhattacharya, Nick Carruthers, Peter de Boer, Wayne Drevets, John Isaac, Declan Jones, John Kemp, Hartmuth Kolb, Jeff Nye, Gayle Wittenberg, Gareth Barker, Anna Bogdanova, Heidi Byrom, Diana Cash, Annamaria Cattaneo, Daniela Enache, Tony Gee, Caitlin Hastings, Melisa Kose, Giulia Lombardo, Nicole Mariani, Anna McLaughlin, Maria Nettis, Naghmeh Nikkheslat, Carmine Pariante, Karen Randall, Julia Schubert, Luca Sforzini, Hannah Sheridan, Camilla Simmons, Nisha Singh, Federico Turkheimer, Vicky Van Loo, Marta Vicente Rodriguez, Toby Wood, Courtney Worrell, Zuzanna Zajkowska, Brian Campbell, Jan Egebjerg, Hans Eriksson, Francois Gastambide, Karen Husted Adams, Ross Jeggo, Thomas Moeller, Bob Nelson, Niels Plath, Christian Thomsen, Jan Torleif Pederson, Stevin Zorn, Catherine Deith, Scott Farmer, John McClean, Andrew McPherson, Nagore Penandes, Paul Scouller, Murray Sutherland, Mary Jane Attenburrow, Jithen Benjamin, Helen Jones, Fran Mada, Akintayo Oladejo, Katy Smith, Rita Balice-Gordon, Brendon Binneman, James Duerr, Terence Fullerton, Veeru Goli, Zoe Hughes, Justin Piro, Tarek Samad, Jonathan Sporn, Liz Hoskins, Charmaine Kohn, Lauren Wilcock, Franklin Aigbirhio, Junaid Bhatti, Ed Bullmore, Sam Chamberlain, Marta Correia, Anna Crofts, Tim Fryer, Martin Graves, Alex Hatton, Manfred Kitzbichler, Mary-Ellen Lynall, Christina Maurice, Ciara O'Donnell, Linda Pointon, Peter St George Hyslop, Lorinda Turner, Petra Vertes, Barry Widmer, Guy Williams, Jonathan Cavanagh, Alison McColl, Robin Shaw, Erik Boddeke, Alison Baird, Stuart Clare, Phil Cowen, I-Shu (Dante) Huang, Sam Hurley, Simon Lovestone, Alejo Nevado-Holgado, Elena Ribe, Anviti Vyas, Laura Winchester, Madeleine Cleal, Diego Gomez-Nicola, Renzo Mancuso, Hugh Perry, Mara Cercignani, Charlotte Clarke, Alessandro Colasanti, Neil Harrison, Rosemary Murray, Jason O'Connor, and Howard Mount
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medicine.medical_specialty ,Cognitive Neuroscience ,050105 experimental psychology ,Body Mass Index ,C-reactive protein ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Receptors, GABA ,Interquartile range ,Internal medicine ,medicine ,Translocator protein ,Humans ,0501 psychology and cognitive sciences ,Radiology, Nuclear Medicine and imaging ,Prefrontal cortex ,Biological Psychiatry ,Anterior cingulate cortex ,Inflammation ,Depressive Disorder, Major ,biology ,business.industry ,Depression ,05 social sciences ,Microglia ,PET ,TSPO ,medicine.disease ,Isoquinolines ,Archival Report ,Endocrinology ,medicine.anatomical_structure ,Positron-Emission Tomography ,biology.protein ,Major depressive disorder ,Neurology (clinical) ,business ,Body mass index ,030217 neurology & neurosurgery - Abstract
Background: Immune mechanisms have been implicated in the pathogenesis of depression. Translocator protein (TSPO)–targeted positron emission tomography (PET) has been used to assess neuroinflammation in major depressive disorder. We aimed to 1) test the hypothesis of significant case-control differences in TSPO binding in the anterior cingulate cortex, prefrontal cortex, and insula regions; and 2) explore the relationship between cerebral TSPO binding and peripheral blood C-reactive protein (CRP) concentration. Methods: A total of 51 depressed subjects with Hamilton Depression Rating Scale score >13 (median 17; interquartile range, 16–22) and 25 healthy control subjects underwent dynamic brain 11C-PK11195 PET and peripheral blood immune marker characterization. Depressed subjects were divided into high CRP (>3 mg/L; n = 20) and low CRP (2 p = .09; F 1,71 = 6.97, p = .01), which was not influenced by body mass index. The case-control difference was greatest in the anterior cingulate cortex (d = 0.49; t 74 = 2.00, p = .03) and not significant in the prefrontal cortex or insula (d = 0.27 and d = 0.36, respectively). Following CRP stratification, significantly higher TSPO binding was observed in low-CRP depression compared with controls (d = 0.53; t 54 = 1.96, p = .03). These effect sizes are comparable to prior major depressive disorder case-control TSPO PET data. No significant correlations were observed between TSPO and CRP measures. Conclusions: Consistent with previous findings, there is a modest increase in TSPO binding in depressed patients compared with healthy control subjects. The lack of a significant correlation between brain TSPO binding and blood CRP concentration or body mass index poses questions about the interactions between central and peripheral immune responses in the pathogenesis of depression.
- Published
- 2021