MS and depression – testing the relationship

Depression and MS

Depression is common in people with MS. One study found that depression is up to 70% more common in someone living with MS than the population as a whole. There seems to be a relationship between MS and depression, but its nature is unclear. There is overlap in symptoms: similar to depression, MS can cause fatigue, concentration difficulties, sleeping problems, and changes in appetite or weight. There may also be overlap in the origins of MS and depression. This article summarises the work of a Swedish group trying to untangle the relationship between MS and depression, and explains the method they used.

Mendelian randomisation – looking at the cards we’ve been dealt

When we are born, our genes are passed down from our parents. In those genes, errors or variants occur all the time. Some can be helpful, such as reducing our chance of a certain disease. Many are harmless, such as affecting how we perceive taste, or an ability to handle spicy foods. Others may increase our risk of disease. The risk of developing a disease can also be affected by changes to the environment, such as a stressful event – or a combination of genetics and the environment.

When thinking about genetic variants, it is important to remember that some variants can affect several functions of the human body, while others affect only one trait. If a variant is likely to affect only one trait, we can use this to our advantage. We can use this to study cause and effect – to say if these genetic changes cause a risk of disease. This is achieved through a method called ‘Mendelian randomisation’. Don’t let the futuristic name put you off – this method simply groups people based on which variants they have, and avoiding factors that we cannot control – such as the environment.

Can Mendelian randomisation help us understand the relationship between depression and MS?

A group at the Karolinska Institute in Sweden aimed to understand the connection between depression and MS. They wanted to see if studying genetics could explain why depression is common in people with MS. The questions they asked were: ‘Can genetic variants linked to MS cause depression? Or is the opposite true: can genetic variants linked to depression cause MS’? They used Mendelian randomisation to understand this relationship, looking only at the risk caused by the variants, without the environmental factors.

The Swedish team looked at the data two huge genetic studies: one focused on MS and one for a major depression disorder. In this type of study, you look for genetic variants in thousands of people. If variants are more common in people with MS than in people who do not have MS, that variant may be involved in increasing the risk of MS. From the hundreds of thousands of people in the two studies, the team found 168 variants linked to MS risk and 96 variants linked to risk of depression. They then used Mendelian randomisation to test the question of whether MS causes depression or vice versa.

Interestingly, the Swedish group did not find a genetic link between MS and the risk of depression.

Despite the increased risk of depression in people with MS, this suggests we cannot explain the link between MS and depression using genetic variants alone. It seems other factors such as the environment also play a role in explaining this relationship.

Conclusion

In brain disorders like MS and depression, the genetics, environments, and symptoms overlap, making it difficult to untangle their origins. More studies are needed to clarify the relationship between MS and depression – and perhaps Mendelian randomisation can lend an unbiased hand.

Getting help

Depression is common in people with MS. If you think you may be experiencing depression, reach out to a professional and family and/or friends. Opening up may be difficult, but it is the best route to recovery. Depression can be managed and help is never far away.