“Missing link” between brain and body inflammatory signals identified in the skull

New research from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London provides valuable insights into the brain-body immune connection identifying key communication hubs in the dural sinuses and skull bone marrow at the back of the head. 

The research, which was supported by funding from the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre (BRC) and published in the journal Brain, used neuroimaging techniques to establish that the dural sinuses, a region at the back of the head that drains deoxygenated blood from the brain, as well as the skull bone marrow act as a likely interface between the central and peripheral immune systems. 

 While the central immune system protects the brain from infection and disease, the peripheral immune system monitors and responds to threats to the rest of the body. Traditionally thought to function independently due to the protective blood-brain barrier, this study highlights a potential link between the two systems, suggesting they could influence one another via other mechanisms.  

Previous research has observed significant elevations in inflammatory markers in both the brain and the body in depression, but no direct correlation has been established.  

Researchers analysed a dataset of 51 adults with depression, as well as 25 healthy age matched participants that were originally recruited as part of the BIODEP study to investigate the role of inflammatory processes in depression. Each subject provided a blood sample before undergoing a PET scan and MRI during the original data collection. Peripheral inflammatory markers were assessed from blood while inflammatory activity in the anterior cingulate cortex, skull marrow, and dural sinuses was assessed with PET sensitive to immune cell density. 

An analysis of the data revealed that the inflammatory activity in dural sinuses and skull marrow, which the researchers identified as a potential reservoir of immune cells, is closely associated with inflammatory activity in both the body and the brain, and this association was present in those with depression and in healthy controls. This association was stronger in the dural sinuses than in the skull marrow. 

Dr Julia Schubert, a research associate at King’s IoPPN and the study’s senior author, said, “Despite extensive research into the central and peripheral immune systems, the skull has always been overlooked as a location of interest in scanning research and discarded as unimportant. 

“Excitingly, our study has established that the interface between skull and brain may be the missing link that we have been looking for – an intermediary between two sets of signals that until now were not clearly correlated.” 

Researchers now want to explore this in greater detail with other conditions to better understand the nature of this relationship.  

Brandi Eiff, the study’s first author from King’s IoPPN said, “There are many conditions for which inflammation is a factor.  By establishing this link, we can better understand how peripheral immunity interacts with brain function and mental health. As science and medicine begins to move toward a more holistic approach, considering the immune responses across the brain and body could be valuable in terms of advancing treatments of many disorders, including depression.” 

Co-author Valeria Mondelli, Clinical Professor of Psychoneuroimmunology at King’s IoPPN and Co-lead of Psychosis and Mood Disorders Theme at the NIHR Maudsley BRC said: “Our study finds that although peripheral and brain inflammation do not seem to be directly associated, there are areas of our skull which appear to work as "traffic lights" between the two.  Focusing on examining levels of inflammation in these areas could give us more precise information of what is happening in the brain and, in the case of depression, identifying those patients in need of treatment that reduces inflammation. Furthermore, these areas could be specifically targeted by future treatment to reduce the effect of increased inflammation in the brain for depression and other immune-related conditions.” 

Ends 

For more information, please contact Patrick O’Brien (Media Manager) on 020 7848 5377. 

Extra-axial inflammatory signal and its relationship to peripheral and central immunity in depression (DOI 10.1093/brain/awae343) (Brandi Eiff, Edward T. Bullmore, Menna R. Clatworthy, Tim D. Fryer, Carmine M. Pariante, Valeria Mondelli, Lucia Maccioni, Nouchine Hadjikhani, Marco L. Loggia, Michael A. Moskowitz, Emiliano Bruner, Mattia Veronese, Federico E. Turkheimer,NIMA Consortium, and Julia J. Schubert) was published in Brain. 

The BIODEP study was jointly sponsored by the Cambridgeshire and Peterborough NHS Foundation Trust and the University of Cambridge. Financial support for the project included a strategic award from the Wellcome Trust in partnership with Janssen Research and Development, GlaxoSmithKline, Lundbeck Foundation and Pfizer.  

About King’s College London and the Institute of Psychiatry, Psychology & Neuroscience   

King’s College London is amongst the top 35 universities in the world and top 10 in Europe (THE World University Rankings 2023), and one of England’s oldest and most prestigious universities.   

With an outstanding reputation for world-class teaching and cutting-edge research, King’s maintained its sixth position for ‘research power’ in the UK (2021 Research Excellence Framework).   

King's has more than 33,000 students (including more than 12,800 postgraduates) from some 150 countries worldwide, and some 8,500 staff. The Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s is a leading centre for mental health and neuroscience research in Europe. It produces more highly cited outputs (top 1% citations) on psychiatry and mental health than any other centre (SciVal 2021), and on this metric has risen from 16th (2014) to 4th (2021) in the world for highly cited neuroscience outputs. In the 2021 Research Excellence Framework (REF), 90% of research at the IoPPN was deemed ‘world leading’ or ‘internationally excellent’ (3* and 4*). World-leading research from the IoPPN has made, and continues to make, an impact on how we understand, prevent and treat mental illness, neurological conditions, and other conditions that affect the brain.  

www.kcl.ac.uk/ioppn | Follow @KingsIoPPN on Twitter, Instagram, Facebook and LinkedIn 

About the National Institute for Health and Care Research (NIHR) 

The mission of the National Institute for Health and Care Research (NIHR) is to improve the health and wealth of the nation through research. We do this by: 

• Funding high quality, timely research that benefits the NHS, public health and social care; 

• Investing in world-class expertise, facilities and a skilled delivery workforce to translate discoveries into improved treatments and services; 

• Partnering with patients, service users, carers and communities, improving the relevance, quality and impact of our research; 

• Attracting, training and supporting the best researchers to tackle complex health and social care challenges; 

• Collaborating with other public funders, charities and industry to help shape a cohesive and globally competitive research system; 

• Funding applied global health research and training to meet the needs of the poorest people in low and middle income countries. 

NIHR is funded by the Department of Health and Social Care. Its work in low and middle income countries is principally funded through UK international development funding from the UK government.