Researchers from the MRC London Institute of Medical Science (LMS) have investigated the way fat tissue works in schizophrenia. Their discoveries might one day lead to better treatments.
Schizophrenia is a neurodevelopmental condition that can cause a range of different symptoms in one’s mind and body. It affects how a person thinks, feels, and behaves. Those living with the condition have a risk of dying that is 2-3 times higher than the general population, and can expect to live up to 15 years less. Heart disease is the leading cause of this additional risk of death in schizophrenia, accounting for 60% of the additional risk.
LMS researchers from the Psychiatric Imaging, Cardiovascular Disease Mechanisms, and Computational Cardiac Imaging groups took part in a multi-disciplinary project to investigate changes in the hearts of patients with schizophrenia. The team compared data from patients and healthy individuals, showing people with schizophrenia display alterations in several blood markers linked with fat (adipose) tissue function, inflammation and liver function. Collectively, these could be responsible for part of the increased cardiovascular risk in people who have schizophrenia.
If confirmed in larger studies, these findings suggest that reparative and preventative strategies that restore balance to the adipose and inflammatory systems could lead to targeted approaches to limit cardiac disease in schizophrenia.
In a previous study published in The British Journal of Psychiatry, LMS researchers suggested people with treated chronic schizophrenia showed heart changes, known as concentric cardiac remodelling (CCR), which could explain part of their increased risk of heart disease, and hence additional risk of death. The causes of CCR can be grouped under two main headings: chronic high blood pressure (hypertensive pathway); or other causes, including changes in fat tissue function, which have also been linked to increased inflammation and liver function abnormalities (non-hypertensive pathway).
To investigate the causes of CCR observed in people with schizophrenia, LMS researchers collected cardiac and whole-body fat MRIs, as well as blood assessment of metabolic and inflammatory markers from people with schizophrenia and carefully matched healthy controls. The results, published in Translational Psychiatry indicate that people with schizophrenia might not show increases in adipose tissue volume, nor demonstrate activation of the hypertensive CCR pathway; instead, they might show evidence of dysfunction in their adipose tissue. This dysfunction was associated with an increase in inflammatory processes, such as increased C-reactive protein (CRP) levels, insulin resistance, and decreased production of adiponectin, a hormone involved in glucose regulation.
Dr Emanuele Osimo, LMS Chain Florey Clinical Research Fellow and first author of the paper said: “By combining cardiac and whole-body fat MRI imaging with blood assessment of metabolic and inflammatory markers, we were able to pinpoint a molecular pathway, which may be responsible for part of the increase in concentric cardiac remodelling (CCR) in people with schizophrenia.
In the general population, CCR tends to be associated with high blood pressure. However, we have shown that this is not the case in people with schizophrenia.”
Professor Oliver Howes, Head of the Psychiatric Imaging group at the LMS commented on the translational impact of the research: “The role of adipose tissue dysfunction in schizophrenia, and in particular the role of circulating adiponectin levels, could provide a useful biomarker to classify cardiovascular risk in patients with schizophrenia. Our work raises the potential for therapeutic avenues to reduce cardiovascular risk.”
‘Adipose tissue dysfunction, inflammation, and insulin resistance: alternative pathways to cardiac remodelling in schizophrenia. A multimodal, case–control study’ was published in Translational Psychiatry on 6 December 2021.
