Many of us experience poor mental health at some point during our lives, whether it’s mild or severe, brief or prolonged. We know something’s going on in the mind, but are there any biological differences in the body?
One way to explore this question is to measure molecules in the blood, which is one of the easiest bodily systems to take samples from. Previous “case-control” studies – which examine differences between healthy people and those diagnosed with a mental health condition – have found differences in the levels of specific molecules, suggesting that several biological processes go hand-in-hand with poor mental health. One such process is inflammation, which is the immune system’s response to damage and infection, and which can become out-of-control when we are repeatedly stressed. While case-control studies are useful, they aren’t designed to look at the population as a whole, and so may lack people with milder symptoms, multiple diagnoses, or those from certain age groups, geographic regions and socioeconomic circumstances. If we look at a large and inclusive group of people, our understanding of mental health might be improved.
Our study
We used data from Understanding Society, the UK Household Longitudinal Study, (UKHLS) to examine the levels of blood molecules called proteins, and whether they are linked to mental health symptoms in participants aged 16 and over. UKHLS is designed to represent all ages, geographic regions and socioeconomic circumstances of people in the UK. Instead of defining people as healthy or unwell, mental health was measured by asking participants questions about their happiness, confidence and ability to cope in recent weeks. The answers to these questions were added up to give two widely-used measures of mental health: psychological distress and quality of life. 184 different proteins were measured, and these probably work together to carry out biological processes in the body. To measure these underlying processes, we used a statistical technique called factor analysis which found 28 “factors”. Each factor can be thought of as a biological process which is measured using a “cocktail recipe” of the 184 proteins. We found that ten of the 28 factors were associated with mental health. To understand which ten biological processes were represented by the factors, we looked at each cocktail recipe and researched the three most important “ingredients” (i.e. proteins!)
Biological processes linked to mental health
Of the ten factors linked to mental health, two seem to represent aspects of inflammation, and a third seems to represent immune cells which fight viruses and cancer. Another represents a chemical pathway which gets “dialled up” during inflammation and disrupts serotonin creation while also producing “neurotoxic” chemicals which kill brain cells. Accordingly, a fifth factor represents a range of “neuroprotective” processes which preserve brain cells. Other factors seem to represent synapse biology, muscle biology, blood clotting, oxidative stress and neurodevelopment. These ten biological processes have been linked to mental health before, often in severe mental health conditions. Our study is interesting because it suggests that these biological processes are also linked to mental health in the general population.
What does this mean?
More research is needed to understand what these associations mean. For example, we don’t know whether each biological process is a cause or a consequence of poor mental health, although existing research suggests that, for inflammation, it goes both ways. We are a long way from being able to use blood tests for the diagnosis, prognosis or treatment of poor mental health, but our study may be a step in the right direction.
Dearman, A., Bao, Y., Schalwyck, L., Kumari, M. (2025). Serum Proteomic Correlates of Mental Health Symptoms in a Representative UK Population Sample. Brain, Behavior and Immunity – Health. Volume 44, March 2025, 100947. Available at: https://doi.org/10.1016/j.bbih.2025.100947