The mental health of people in the UK and worldwide is getting worse. Common conditions like depression and anxiety have risen by more than 20 per cent since the 1990s. Although much of the blame in recent years has been directed at social media platforms (perhaps not unreasonably), we may have overlooked another significant factor: our physical health.
Dopamine is probably one of the most misunderstood chemicals in the brain
Mental health is one of the few areas of medicine that has been bucking an otherwise positive trend of generally reduced illness and mortality. Another? Metabolic disease, in particular obesity and type-2 diabetes, which have risen more or less in tandem with mental health problems over the last 30 years.
Neuroscientists like myself are now beginning to ask whether these trends are connected: could the rise in metabolic disease be influencing, even causing, the increase in mental health problems like depression?
The epidemiological evidence is substantial. A cluster of conditions together called the metabolic syndrome – high blood sugar, obesity, heart disease and high blood pressure – all substantially increase an individual’s risk of developing depression. At first glance, the explanation is obvious: society doesn’t treat people who are overweight or obese especially kindly; coupled with the stress of managing a chronic illness, this is enough to make anyone feel low. But there seems to be something deeper going on, and it involves the neurotransmitter dopamine.
Dopamine is probably one of the most misunderstood chemicals in the brain. In the media shorthand it is often described as the ‘feel-good hormone’, but in reality dopamine has very little to do with the subjective experience of pleasure, and much more to do with desire. Dopamine is what makes you want things – as you interact with the world and anticipate experiencing a positive event or outcome, dopamine is released, enhancing your motivation. The more dopamine is released, the more work you are willing to do to obtain that reward.
This sense of desire is exactly what is missing in depression. People with depression often describe feeling not sad as such, but simply grey – the prospect of leaving the house, seeing friends, doing activities they formerly enjoyed literally does not move them anymore. Changes in dopamine signalling might therefore be responsible for the motivational problems and loss of drive seen in depression.
A few years ago, however, I made a rather strange discovery. A friend sent me a paper showing that dopamine also controls our blood sugar levels. It was like finding a hidden room in a house where I had already lived for many years. Drugs which increase levels of dopamine in the brain, with which I was very familiar as a neuroscientist, were also being used in a completely different context to treat diabetes. As scientists, we pay lip service to the notion of interdisciplinarity, but this was the first time that I realised how much can go missing in the chasms between different fields.
Just as dopamine has this unexpected role in regulating our blood sugar, so too is it influenced by our metabolism in turn. Hormones like insulin and leptin, which principally control blood sugar and body fat respectively, also stimulate dopamine release in the brain and, at least in mice, seem to boost motivation. Spurred by these findings, my colleagues and I have begun to investigate how loss of sensitivity to insulin in humans, a hallmark of type-2 diabetes, might contribute to the symptoms of depression.
We are not the first people to begin thinking this way. Together, the field is beginning to converge on what seems to be a distinct subtype of ‘metabolic depression’, constituting up to 40 per cent of cases. This is part of a broader movement in neuroscience seeking to integrate our understanding of the mind with the body – focussing on the brain in isolation, like trying to study a computer without plugging in the screen, has unsurprisingly brought only limited insights.
Crucially, metabolic depression is defined as much by physical symptoms (increased appetite, fatigue and sleeping) as it is by psychological symptoms like low mood and motivation. Indeed we are beginning to put the lie to the idea that mental health problems are purely mental – often patients themselves report that it is the bodily symptoms that bring the most distress. In the case of depression, it might be better in some cases to think of it as a disorder of energy regulation.
As we begin to characterise the underlying biological pathways, it may even be possible further down the line to develop specific blood tests or other objective markers that would help us to identify this type of depression – this would be a first for depression research, and a huge advance for the field.
Given the connection between depression and metabolic disease, our public health is clearly something that we urgently need to address. The science is clear – aerobic exercise, for example, is a very effective antidepressant, and for some people may be equal to first-line treatments like therapy or medication. Translating this into public policy, and understanding how as a society we can improve our diets and activity levels, and turn back 30 years of decline, will however be a much thornier problem to solve.
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