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

NIMA Consortium

doi:10.1016/j.bpsc.2020.12.017

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

NIMA Consortium

Research output: Contribution to journal › Article › peer-review

14 Citations (Scopus)

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 (<3 mg/L; n = 31). Results: Across the three regions, TSPO binding was significantly increased in depressed versus control subjects (η²_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; 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. 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.

Original language	English
Pages (from-to)	716-724
Number of pages	9
Journal	Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
Volume	6
Issue number	7
DOIs	https://doi.org/10.1016/j.bpsc.2020.12.017
Publication status	Published - Jul 2021

Keywords

C-reactive protein
Depression
Inflammation
Microglia
PET
TSPO

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10.1016/j.bpsc.2020.12.017

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@article{5015f9445d244bcabc9376fb9e72e944,

title = "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",

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 (<3 mg/L; n = 31). Results: 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. 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.",

keywords = "C-reactive protein, Depression, Inflammation, Microglia, PET, TSPO",

author = "{NIMA Consortium} and Julia Schubert and Mattia Veronese and Fryer, {Tim D.} and Roido Manavaki and Kitzbichler, {Manfred G.} and Maria Nettis and Valeria Mondelli and Pariante, {Carmine M.} and Bullmore, {Edward T.} and Dominika Wlazly and Amber Dickinson and Andy Foster and Clare Knight and Claire Leckey and Paul Morgan and Angharad Morgan and Caroline O'Hagan and Samuel Touchard and Shahid Khan and Phil Murphy and Christine Parker and Jai Patel and Gareth Barker and Diana Cash and Annamaria Cattaneo and Tony Gee and Caitlin Hastings and Melisa Kose and Giulia Lombardo and Nicole Mariani and Anna McLaughlin and Maria Nettis and Naghmeh Nikkheslat and Pariante, {Carmine M.} and Karen Randall and Julia Schubert and Luca Sforzini and Hannah Sheridan and Camilla Simmons and Nisha Singh and Turkheimer, {Federico E.} and {Van Loo}, Vicky and Rodriguez, {Marta Vicente} and Courtney Worrell and Zuzanna Zajkowska and Helen Jones and Alison Baird and Simon Lovestone and Alessandro Colasanti and Turkheimer, {Federico E.}",

note = "Funding Information: The BIODEP study was sponsored by the Cambridgeshire and Peterborough NHS Foundation Trust and the University of Cambridge. This work was supported by a strategic award from the Wellcome Trust (Grant No. 104025 [to ETB, CMP, FET]) in partnership with Janssen, GlaxoSmithKline, Lundbeck, and Pfizer; a Senior Investigator award from the National Institute of Health Research (NIHR) (to ETB and CMP); NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London; and the NIHR Cambridge Biomedical Research Centre (Mental Health). Recruitment of participants was supported by the NIHR Clinical Research Network: Kent, Surrey and Sussex, and Eastern. Study data were collected and managed using REDCap (Research Electronic Data Capture) electronic data capture tools hosted at the University of Cambridge (71). We gratefully thank all study participants, research teams, and laboratory staff, without whom this research would not have been possible. We thank the reviewers for their thoughtful comments and suggestions. A previous version of this article was published as a preprint on medRxiv: https://www.medrxiv.org/content/10.1101/2020.06.04.20099556v1. The authors report no biomedical financial interests or potential conflicts of interest. Publisher Copyright: {\textcopyright} 2021 Society of Biological Psychiatry Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = jul,

doi = "10.1016/j.bpsc.2020.12.017",

language = "English",

volume = "6",

pages = "716--724",

journal = "Biological Psychiatry: Cognitive Neuroscience and Neuroimaging",

issn = "2451-9022",

publisher = "Elsevier Inc.",

number = "7",

}

TY - JOUR

T1 - 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

AU - NIMA Consortium

AU - Schubert, Julia

AU - Veronese, Mattia

AU - Fryer, Tim D.

AU - Manavaki, Roido

AU - Kitzbichler, Manfred G.

AU - Nettis, Maria

AU - Mondelli, Valeria

AU - Pariante, Carmine M.

AU - Bullmore, Edward T.

AU - Wlazly, Dominika

AU - Dickinson, Amber

AU - Foster, Andy

AU - Knight, Clare

AU - Leckey, Claire

AU - Morgan, Paul

AU - Morgan, Angharad

AU - O'Hagan, Caroline

AU - Touchard, Samuel

AU - Khan, Shahid

AU - Murphy, Phil

AU - Parker, Christine

AU - Patel, Jai

AU - Barker, Gareth

AU - Cash, Diana

AU - Cattaneo, Annamaria

AU - Gee, Tony

AU - Hastings, Caitlin

AU - Kose, Melisa

AU - Lombardo, Giulia

AU - Mariani, Nicole

AU - McLaughlin, Anna

AU - Nettis, Maria

AU - Nikkheslat, Naghmeh

AU - Pariante, Carmine M.

AU - Randall, Karen

AU - Schubert, Julia

AU - Sforzini, Luca

AU - Sheridan, Hannah

AU - Simmons, Camilla

AU - Singh, Nisha

AU - Turkheimer, Federico E.

AU - Van Loo, Vicky

AU - Rodriguez, Marta Vicente

AU - Worrell, Courtney

AU - Zajkowska, Zuzanna

AU - Jones, Helen

AU - Baird, Alison

AU - Lovestone, Simon

AU - Colasanti, Alessandro

AU - Turkheimer, Federico E.

N1 - Funding Information: The BIODEP study was sponsored by the Cambridgeshire and Peterborough NHS Foundation Trust and the University of Cambridge. This work was supported by a strategic award from the Wellcome Trust (Grant No. 104025 [to ETB, CMP, FET]) in partnership with Janssen, GlaxoSmithKline, Lundbeck, and Pfizer; a Senior Investigator award from the National Institute of Health Research (NIHR) (to ETB and CMP); NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London; and the NIHR Cambridge Biomedical Research Centre (Mental Health). Recruitment of participants was supported by the NIHR Clinical Research Network: Kent, Surrey and Sussex, and Eastern. Study data were collected and managed using REDCap (Research Electronic Data Capture) electronic data capture tools hosted at the University of Cambridge (71). We gratefully thank all study participants, research teams, and laboratory staff, without whom this research would not have been possible. We thank the reviewers for their thoughtful comments and suggestions. A previous version of this article was published as a preprint on medRxiv: https://www.medrxiv.org/content/10.1101/2020.06.04.20099556v1. The authors report no biomedical financial interests or potential conflicts of interest. Publisher Copyright: © 2021 Society of Biological Psychiatry Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/7

Y1 - 2021/7

N2 - 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 (<3 mg/L; n = 31). Results: 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. 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.

AB - 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 (<3 mg/L; n = 31). Results: 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. 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.

KW - C-reactive protein

KW - Depression

KW - Inflammation

KW - Microglia

KW - PET

KW - TSPO

UR - http://www.scopus.com/inward/record.url?scp=85103715769&partnerID=8YFLogxK

U2 - 10.1016/j.bpsc.2020.12.017

DO - 10.1016/j.bpsc.2020.12.017

M3 - Article

C2 - 33515765

AN - SCOPUS:85103715769

SN - 2451-9022

VL - 6

SP - 716

EP - 724

JO - Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

JF - Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

IS - 7

ER -

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

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