Collaboration & Innovation Current Projects

People living with severe mental health conditions often face complex challenges, not only related to their mental health, but also to their physical health and long-term quality of life. Mental health conditions are closely linked with the body’s biology. These links run both ways: mental illness can affect the body, and the mental health can be shaped by genes, physical health, and the lasting effects of life experiences on mind and body. 

To understand these connections, we need large studies that measure biological markers (biomarkers) – such as proteins, metabolic markers, and genes – alongside information about people’s health and experiences. 

This project will bring together researchers across the UK to collect and study blood samples from people with severe mental illness, including depression, bipolar disorder, psychosis, and complex emotions, and from people without these conditions. We will measure a wide range of biological features and link them to detailed information on mental health symptoms, life experiences, and physical health. By using the same methods in five UK research hubs, we will create a powerful collection of data including a diverse range of participants. This will allow future researchers to explore many questions, for example, how blood-based patterns relate to symptoms, recovery, or treatment response, and why some people with mental illness also develop other health problems. 

People with lived experience of mental illness are helping to shape the project at every stage, from how samples are collected to how the data will be used. The result will be a unique UK resource that will support research for many years to come. We hope it will lead to a better understanding of mental illness, the discovery of new treatments, and more personalised care for those affected.

People with severe mental illnesses (SMI), such as schizophrenia and bipolar disorder, face profound health inequalities, dying on average 15 to 20 years earlier than the general population. The primary cause of this gap is avoidable inequalities in society, meaning the conditions people are born, grow, live, work and age which accumulate over a lifetime (referred to as the "exposome"). This unequal distribution of social determinants of health, such as deprivation, loneliness, childhood experiences, discrimination which drives inequalities in physical and mental health although mechanisms are complex and inter-related.

The Core Problem

The grant addresses the critical link between social circumstances and poor physical health in individuals with SMI. These stressors can cause chronic physiological changes, making individuals more vulnerable to conditions like high blood pressure, diabetes, and obesity.

Why Current Data Falls Short

Current large-scale health studies often overlook or inconsistently measure these vital social factors in people with SMI, leading to crucial gaps in our knowledge. This makes it difficult for researchers and policymakers to develop targeted prevention strategies.

Our Project Goals and Impact

This innovative project aims to tackle these issues head-on by:

• Harmonizing Data: Creating a platform-wide consensus and a catalogue of discoverable, interactive, and customizable social stress measures in Mental Health Platform and other SMI cohorts “exposome tables”.
• Uncovering Mechanisms: Use this enhanced data to understand which social stress factor(s) drive biggest health disparities, providing actionable targets for new interventions and preventative measures.
• Driving Policy Change: Involving individuals with lived experience at every stage to ensure the findings inform clinical practice and policy, ultimately closing the decades-long life expectancy gap for people with severe mental illness.

By understanding the full picture of their physical and social environments, we can move beyond simply treating symptoms and focus on preventing illness, leading to healthier, longer lives for a highly vulnerable population. 

People with severe mental illness (SMI) such as schizophrenia, bipolar disorder and severe depression die 10–20 years earlier than the general population, often from preventable heart disease and diabetes. Medications called glucagon-like peptide-1 receptor agonists (GLP-1RAs; including semaglutide, widely known as Ozempic) can help with weight loss and diabetes, but we do not yet know how they affect mental health. Thousands of people with SMI in the UK are already taking these medications, and numbers are growing rapidly, yet doctors have no way of knowing which patients might experience mental health problems and which might benefit.

This project aims to find out why people with SMI respond differently to these medications, and to identify who may be at risk of adverse outcomes. Using NHS health records from across the UK, we will investigate four possible explanations: whether losing weight too quickly causes mental health symptoms; whether the body's inflammatory response plays a role; whether other psychiatric medications interact with GLP-1RA treatments; and whether certain combinations of patient characteristics, such as diagnosis, illness history, and physical health, predict who will do well or badly. We will work closely with people who have lived experience of SMI and physical health problems throughout the project, ensuring that our findings reflect what matters most to patients.

The results will be used to build a simple online tool that clinicians can use when deciding whether to prescribe these medications to someone with SMI. By identifying which patients are at higher or lower risk, we aim to help doctors make safer, more personalised prescribing decisions, so that people with SMI can benefit from these treatments without unnecessary harm to their mental health. We will share our findings with the National Institute for Health and Care Excellence and the Royal College of Psychiatrists to help shape national prescribing guidance.

Schizophrenia is a serious mental health condition that affects how people think, perceive reality, and experience the world around them. It usually begins in early adulthood and can profoundly affect education, employment, relationships, and quality of life. About one in four people with schizophrenia develop treatment-resistant schizophrenia, meaning that mental health symptoms do not improve despite trying several different antipsychotic medicines. For these individuals, clozapine - a type of antipsychotic medicine - is the most effective treatment. It is often the only medicine that can meaningfully reduce symptoms, prevent relapse, and help people regain stability and independence. However, clozapine can also cause important physical health side effects. Many people gain significant weight after starting treatment, increasing the risk of diabetes and heart disease. Clozapine can also affect the immune system and cause serious heart inflammation. As a result, people with treatment resistant schizophrenia can face a difficult dilemma: the medicine that offers the greatest chance of recovery from severe mental health symptoms also carries risks for physical health. Finding ways to reduce these risks, while preserving the mental health benefits of clozapine, is therefore an urgent priority.

Scientists do not fully understand why clozapine affects the heart, but growing evidence suggests this may involve changes in metabolism - the way the body processes and uses energy - and inflammation. This project will investigate these mechanisms and explore whether newer medicines used to treat obesity and diabetes, called GLP-1 receptor agonists, might help protect the heart.

First, we will follow people starting clozapine and use specialised heart MRI scans and blood tests to understand how the drug affects the heart, immune system, and metabolism. Second, we will analyse genetic data to see whether these biological changes overlap with genes linked to heart disease and schizophrenia. Third, in laboratory experiments we will test how clozapine affects human heart cells and whether tirzepatide, one of the GLP-1 receptor agonist medicines, can prevent these harmful effects. Finally, we will study the real-world use of tirzepatide in NHS services to understand how effective and acceptable it is for people taking clozapine. By improving our understanding of how to protect physical health during clozapine treatment, this research aims to help people with treatment-resistant schizophrenia live longer, healthier lives