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
Julia Schubert, Mattia Veronese, Tim D. Fryer, Roido Manavaki, Manfred G. Kitzbichler, Maria Antonietta Nettis, Valeria Mondelli, Carmine M. Pariante, Edward T. Bullmore, Dominika Wlazly, Amber Dickinson, Andy Foster, Clare Knight, Claire A. Leckey, Paul T. Morgan, Angharad R. Morgan, Caroline O’Hagan, Samuel Touchard, Shahid A. Khan, Phil Murphy, Christine A. Parker, Jai Patel, Jill Richardson, Paul D. Acton, Nigel Austin, Anindya Bhattacharya, Nick Carruthers, Peter de Boer, Wayne C. Drevets, John Isaac, Declan N.C. Jones, John A. Kemp, Hartmuth C. Kolb, Jeff Nye, Gayle Wittenberg, Gareth J. Barker, Anna Bogdanova, Heidi Byrom, Diana Cash, Annamaria Cattaneo, Daniela Enache, Antony D. Gee, Caitlin Hastings, Melisa Kose, Giulia Lombardo, Nicole Mariani, Anna McLaughlin, Valeria Mondelli, Maria Antonietta Nettis, Naghmeh Nikkheslat, Carmine M. Pariante, Karen Randall, Julia Schubert, Luca Sforzini, Hannah Sheridan, Camilla Simmons, Nisha Singh, Federico Turkheimer, Vicky Van Loo, Mattia Veronese, Marta Vicente‐Rodríguez, Toby Wood, Courtney Worrell, Zuzanna Zajkowska, Brian Campbell, Jan Egebjerg, Hans Eriksson, François Gastambide, Karen Husted Adams, Ross Jeggo, Thomas Möeller, Bob Nelson, Niels Plath, Christian Thomsen, Jan Pederson, Stevin H. 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 D. Smith, Rita J. Balice‐Gordon, Brendon Binneman, James M. Duerr, Terence Fullerton, Veeru Goli, Zoë A. Hughes, Justin R. Piro, Tarek A. Samad, Jonathan Sporn, Liz Hoskins, Charmaine Kohn
Abstract
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. 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 (<3 mg/L; n = 31). Across the three regions, TSPO binding was significantly increased in depressed versus control subjects (η2p = .09; F1,71 = 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; t74 = 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; t54 = 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. 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.