Extra-axial inflammatory signal and its relationship to peripheral and central immunity in depression
Although both central and peripheral inflammation have been observed consistently in depression, the relationship between the two remains obscure. Extra-axial immune cells may play a role in mediating the connection between central and peripheral immunity. This study investigates the potential roles of calvarial bone marrow and parameningeal spaces in mediating interactions between central and peripheral immunity in depression. PET was used to measure regional TSPO expression in the skull and parameninges as a marker of inflammatory activity. This measure was correlated with brain TSPO expression and peripheral cytokine concentrations in a cohort enriched for heightened peripheral and central immunity comprising 51 individuals with depression and 25 healthy controls. The findings reveal a complex relationship between regional skull TSPO expression and both peripheral and central immunity. Facial and parietal skull bone TSPO expression showed significant associations with both peripheral and central immunity. TSPO expression in the confluence of sinuses was also linked to both central and peripheral immune markers. Group-dependent elevations in TSPO expression within the occipital skull bone marrow were also found to be significantly associated with central inflammation. Significant associations between immune activity within the skull, parameninges, parenchyma and periphery highlight the role of the skull bone marrow and venous sinuses as pivotal sites for peripheral and central immune interactions.
Authors
- Tim D. Fryer (ORCID: https://orcid.org/0000-0003-1555-9790)
- Emiliano Bruner (ORCID: https://orcid.org/0000-0002-6686-4616)
- Mattia Veronese (ORCID: https://orcid.org/0000-0003-3562-0683)
- Edward Thomas Bullmore (ORCID: https://orcid.org/0000-0002-8955-8283)
- Julia Schubert (ORCID: https://orcid.org/0000-0001-6102-7272)
- Valeria Mondelli (ORCID: https://orcid.org/0000-0001-8690-6839)
- Marco L. Loggia (ORCID: https://orcid.org/0000-0002-8026-5265)
- Federico Turkheimer (ORCID: https://orcid.org/0000-0002-3766-3815)
- Menna Ruth Clatworthy (ORCID: https://orcid.org/0000-0002-3340-9828)
- Carmine M. Pariante (ORCID: https://orcid.org/0000-0002-9132-5091)
- Nouchine Hadjikhani (ORCID: https://orcid.org/0000-0003-4075-3106)
- Brandi Eiff (ORCID: https://orcid.org/0000-0003-3153-4307)
- Lucia Maccioni (ORCID: https://orcid.org/0000-0002-6564-2827)
- Michael A. Moskowitz
Institutions
- Harvard University (US)
- University of Padua (IT)
- King's College London (GB)
- University of Cambridge (GB)
- Instituto de Salud Carlos III (ES)
- Cambridge University Hospitals NHS Foundation Trust (GB)
- Massachusetts General Hospital (US)
- Museo Nacional de Ciencias Naturales (ES)
- Athinoula A. Martinos Center for Biomedical Imaging (US)
- Cambridgeshire and Peterborough NHS Foundation Trust (GB)
- Fundacion Centro De Investigacion De Enfermedades Neurologicas (ES)
- Imaging Center (US)
Publication Details
- Journal
- Brain
- Published
- 2024-12-10
- DOI
- https://doi.org/10.1093/brain/awae343
- Citations
- 15
- Primary Topic
- Tryptophan and brain disorders
- Type
- article
- Field-Weighted Citation Impact
- 2.36
Funders
- Pfizer
- GlaxoSmithKline
- Wellcome Trust
- GlaxoSmithKline España
- National Institute for Health and Care Research
- Department of Health and Social Care
- University of Cambridge
- King's College London
- H. Lundbeck A/S
- Medical Research Council
- NIHR Oxford Biomedical Research Centre
- NIHR Cambridge Biomedical Research Centre
- Janssen Canada