When can blood markers and mental disorders be linked? Genetics finally allows us to know

Some of the most important mental health disorders, such as depression, schizophrenia and anorexia, are sometimes difficult to identify. Our study of the genetic, biochemical and psychiatric data of almost a million people has just shown that they can be linked to biological markers detected during simple blood tests.

This research will allow us to better understand the causes of mental illness. Our results could even contribute to the identification of new treatments in the future.

A healthy body, a healthy mind

People often consider mental health to be separate from the health of the rest of the body. This is far from true: it is clearly established that many biochemical substances implicated in “physical” diseases, such as diabetes and autoimmune disorders, for example, have a direct impact on the functioning of our brain.

Many studies have also looked at the issue by focusing on substances called “biomarkers”, which can be easily measured in the blood.

A biomarker is simply a chemical or biological substance present in our body, which can be linked to a particular process – for example a disease. There are many categories, many of which relate to what is assessed during a blood test ordered by your doctor, such as cholesterol, blood sugar, liver enzymes, vitamins or markers of inflammation.

Simple blood tests can track biomarkers linked to certain mental disorders.
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Biomarkers tracked in routine blood tests are particularly useful, as they are typically affected by diet, lifestyle, or drug therapy.

The complex role of genetics in mental health

It is often difficult to study the role of these blood biomarkers in mental health disorders. Many studies in this area are not large enough to draw firm conclusions.

One solution is to look at genetic influences on both mental illness and the substances measured in the blood. Genetics is useful because we now have data from millions of individuals who have volunteered to participate in research studies.

Mental illnesses and blood biomarkers are what geneticists call “complex traits.” The particularity of such complex traits is that many genes are involved; environmental factors also contribute.

The ability to access ever-increasing genetic data has allowed us to study how a huge number of tiny changes (a mutation, etc.) in the DNA sequence can be linked to a risk of mental illness. These “variants” can then be linked to measured blood levels of a biomarker.

For example, a given version of a specific gene may increase the risk of developing schizophrenia and may also be linked to decreased levels of a vitamin circulating in the blood. Most of these variations are individually associated with a very small change in risk for a process as complex as the development of mental illness, but they can add up to produce larger effects.

How are blood biomarkers linked to mental illness?

Our recent study sought to use genetics to examine the relationship between nine mental disorders (attention disorder, post-traumatic syndrome, Tourette’s syndrome, autism, depression, OCD, schizophrenia…) and 50 factors measured in blood tests routine: cholesterol, vitamins, enzymes and indicators of inflammation in particular. We used data obtained by very large studies conducted by other teams, and coming from almost a million volunteers in total.

Our analysis first confirmed the existence of what is called a “genetic correlation” between blood biomarkers and mental illness; and that this phenomenon was more widespread than previously thought. Observing a genetic correlation means that the effects of DNA sequence changes on the risk of mental illness and on levels of a given biomarker are more similar to each other than would occur by chance alone.

To take a concrete example, we found a positive genetic correlation between white blood cell count and depression. This could indicate that a process in our body influences both depression and white blood cells.

If we could identify this common process, it could allow us to better understand the causes of depression and target treatment.

Correlation and causality, the eternal difficulty

Our study showed that there is a correlation between the genetics of mental illness and blood factors… But this does not tell us whether blood biomarkers are involved in the causes of mental illness.

To distinguish correlation from medical causation, the gold standard approach is to conduct clinical trials where patients are randomly given a treatment or a placebo. However, these tests are expensive and difficult to perform.

We therefore opted for the following solution: to use DNA variants linked to changes in blood biomarkers to act as a natural clinical trial. This process takes advantage of the fact that we randomly inherit genetic variants from our parents, much like participants in a clinical trial are randomly given a treatment or a placebo.

This is a complex method, the results of which must be interpreted with caution.

We found evidence that certain substances measured in the blood may in fact be involved in the cause of certain mental illnesses. Proteins related to the immune system, for example, may be implicated in depression, schizophrenia and anorexia.

Further work is now needed to determine how precisely these blood measurements are implicated in these disorders. And this to find out if they can be targeted for treatment.

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