People with heart disease are more likely to suffer from depression, and the opposite is also true. Now, MQ-funded scientists at the University of Cambridge believe they have identified a link between these two conditions: inflammation. We spoke to one of the lead investigators, Golam Khandaker, to find out more…
What is the aim of your project?
My colleagues Dr Stephen Burgess, Professor Peter Jones and I wanted to understand the reasons why depression and heart disease often occur together. To do this, we first tested if shared environmental risk factors or shared genetic factors can explain this link. Next, we worked through a list of 15 known risk factors for heart disease, and tested whether any of these are causally linked with depression.
What were your key findings?
We analysed the data of over 367,000 people from the UK Biobank cohort, and identified two important things:
1) The reason people often experience heart disease and depression at the same time arises largely from shared environmental risk factors, rather than shared genetic factors. This finding is important from a public health perspective, because we can start to give advice that could help people reduce their risk of developing these conditions – for example, quitting smoking and exercising.
2) Triglycerides (a fat present in our blood that’s known to be a risk factor for heart disease) and IL-6 and CRP (which are proteins from our blood that indicate inflammation), are both likely to be underlying risk factors for depression.
This is really vital new knowledge, because it suggests to us that inflammation could be a key cause of both depression and heart disease. There are a number of ongoing studies (including our own ongoing clinical trial in Cambridge, the Insight study) testing things like if anti-inflammatory treatment could help some people with depression – and this finding suggests we are on the right track.
What exactly is inflammation - and what are some of the causes?
Inflammation is our body’s natural response to fighting off infection, and it’s essential for survival. However, chronic low-grade inflammation can be harmful. Psychological stress, physical inactivity, obesity, smoking and alcohol can all increase low grade inflammation.
How did you find all of this – can you talk us through the process?
First, we looked at whether family history of heart disease was associated with risk of major depression. We found that people who reported at least one parent having died of heart disease were 20% more likely to develop depression at some point in their life. We then looked at whether genetic predisposition for heart disease was associated with depression – and it wasn’t. This suggests that the reason people often have both depression and heart disease arises more from shared environmental factors rather than shared genes.
We then used a technique known as Mendelian randomisation to investigate 15 biomarkers – biological ‘red flags’ – associated with increased risk of heart disease. Mendelian randomisation is a statistical technique that allows researchers to rule out the influence of factors that would confuse a study, like social status. This was the technique that showed us that triglycerides, IL-6 and CRP are all likely to be causal risk factors for depression.
So what’s the potential now – where can we go with this new information?
First, by showing that inflammation could be a cause for depression – in some people – we’ve provided a new understanding of the causes and potential treatments for depression. Currently these treatments hinge on serotonin, a chemical that helps send messages between different parts of the brain.
This finding supports the idea that anti-inflammatory treatment could be helpful for some people with depression. For example, we’re now conducting a randomised control trial of tocilizumab (a drug that decreases IL-6 activity) to test whether it can improve mood and memory in people with depression who have evidence of low-grade inflammation.
Secondly, now that we know the link between depression and heart disease arises largely from shared environmental risk factors we can start sharing new, informed advice with the public. Our findings suggest that reducing exposure to environmental and lifestyle risk factors associated with these conditions – like smoking, physical inactivity and psychological stress - could reduce the risk of both conditions.
Finally, why do you think it’s important to look at mental and physical health together?
Our work adds to the growing evidence that the mind and body are closely linked - that one influences the other. The immune system is relevant not only for the heart, but also for mood. In a clinical setting, we need to start treating the whole person; psychiatrists need to be mindful of common physical illnesses linked with certain mental illness, and the same goes for physicians.
On a community level, we need to take measures that improve both our physical and mental health. Our work suggests that reducing inflammation could be helpful for both the heart and mind.
