A third of people with depression do not get better after trying two or more antidepressants, and no one knows why. This project tackles that gap by asking whether poor metabolic health—problems with blood sugar, cholesterol, or blood pressure—is part of the answer. The researcher will also examine social factors such as unstable housing, financial strain, and limited access to support, which may make it harder to stay both physically and mentally healthy. If the work succeeds, it could change how doctors treat depression in people with metabolic problems—for example, by combining antidepressants with treatments for diabetes or heart disease risk, or by addressing social barriers that block recovery. The research is not yet testing a specific intervention; it is first establishing the links between metabolic health, social circumstances, and treatment resistance. That fundamental understanding is a necessary step before clinical trials can be designed. Similar work on the biology of depression has already led to new drug targets, so clarifying these connections could eventually reshape how the NHS manages the most stubborn cases of depression.
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Treatment-Resistant Depression (TRD) is a severe form of depression that does not respond adequately to at least two different antidepressants. It causes significant emotional distress, making everyday tasks such as work, relationships, and basic self-care incredibly challenging. Despite its profound impact, little is known about why some individuals respond to antidepressants while others experience TRD, or about the long-term effects of TRD on overall health. My research explores the relationship between TRD and metabolic health. Metabolic health involves how your body manages blood sugar, cholesterol, blood pressure, and fat. Poor metabolic health can lead to type 2 diabetes and heart disease. There are several reasons why TRD and metabolic ill-health could be linked. Firstly, living with poor metabolic health can be emotionally challenging, which may worsen depression and hinder treatment. Secondly, untreated depression can make it harder to lead a healthy lifestyle, resulting in poor metabolic health. Third, biological factors, such as inflammation or hormone imbalances, could influence both metabolic health and the brain’s response to antidepressants. Fourthly, difficulties in everyday life – financial struggles, unstable housing, lack of education or job opportunities, limited access to support, distressing environments – may make it harder to keep physically and mentally healthy. I aim to understand the relationship between TRD and metabolic health, whilst considering the wider context of people’s lives. I aim to identify changes we can make, both clinically and socially, that will help make depression easier to treat in people with poor metabolic health — and will in turn help people with depression maintain better metabolic health.
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