New knowledge could help predict and prevent depression

In a new study, researchers from the Danish iPSYCH project demonstrate that people with the highest genetic propensity are over two and a half times as likely to be treated in a psychiatric hospital for depression compared to people with the lowest propensity. This knowledge could be utilised to strengthen preventative efforts for those who are at risk.

In Denmark, 15.5 per cent of woman and nine per cent of men receive treatment for depression at a psychiatric hospital at some stage of their lives. Depression is a common but very serious condition which is very costly for both the individual and society as a whole.

Researchers have now completed a study in which they followed 34,500 Danes for up to 20 years and measured their genetic risk for developing depression.

“The study showed that the risk of being treated for depression at a psychiatric hospital was more than two and a half times higher for people with a high polygenic risk score,” explains professor at iPSYCH and contributor to the study Esben Agerbo.

Polygenetic means that the disease is not connected to only one disease gene, but to many genes. Put another way, it means there are many genes that determine whether a person is predisposed to developing depression.

“We know that depression is partly determined by genetic factors, and today it’s possible to measure the genetic propensity directly – rather than having to rely on family history as a way of guessing at genetic disposition for developing depression,” explains Esben Agerbo.

The polygenetic score was not related to factors such as mild, moderate, severe or psychotic symptoms, treatment setting or age at the first hospital visit, which could mean that these aspects are determined more by environmental factors.

The results of the study have just been published in the scientific journal JAMA Psychiatry.

“Our hope is that by utilising genetic information in conjunction with known risk factors in the environment, we will be able to develop better methods to identify people who are at risk of developing depression,” says postdoc at iPSYCH, Katherine L. Musliner, who is behind the study.

However, the results also show that the relationship between genetics and mental illness is complex. There is no ‘ depression gene’ and even those with the highest genetic propensity will not necessarily develop depression.

“The ability to identify people with an increased risk of developing depression is useful, because it will make it possible for us to target preventative efforts towards the people who will benefit most from them,” says Katherine L. Musliner.

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iPSYCH was founded back in 2012 when six leading researchers who all work in the field of psychiatry and genetics got together. Their mission was to find the causes of five of the most serious mental disorders; schizophrenia, bipolar disorder (previously manic depression), autism, ADHD and depression. iPSYCH’s purpose was – and still is – to lay the foundations for better treatment and prevention of mental disorders by mapping the factors that play a role in these diseases. By examining genes and risk factors in more than 80,000 Danes who both did and did not suffer from mental disorders, iPSYCH sheds light on the complex interaction between heredity factors and the environment, which for some people results in them developing a mental disorder. The project examines the diseases from various angles, ranging from genes and cells to population studies, prenatal life to adult patient and from cause to symptom. Today iPSYCH is one of the world’s largest studies of genetic and environmental causes of mental disorders and it now comprises more than 150 researchers within psychiatry, genetics and register-based research.

Multiple genes and the way they interact may have significance for whether a person is predisposed to suffer from different diseases. A distinction is made between mono- and polygenetic diseases depending on whether one or multiple genes play a role in disease risk. For the majority of diseases, environmental factors also have a bearing on whether the disease develops. For example, a person may live their whole life with a genetic disposition for depression without ever experiencing a depressive episode. But they may experience depression following events such as shocks or a death in the family etc.

The study is a register-based study.

The partners involved in the study are: Nis Suppli, John McGrath, Jonas Bybjerg-Grauholm, Marie Bækvad-Hansen, Ole Andreassen, Carsten B Pedersen, Marianne G Pedersen, Bipolar Work Group of the PGC and iPSYCH PIs: Ole Mors, Thomas Werge, Merete Nordentoft, David Hougaard, Anders Børglum and Preben Bo Mortensen.

The study is financed by the Lundbeck Foundation.

The scientific article “Association of polygenic liabilities for major depression, bipolar disorder, and schizophrenia with risk for depression in the Danish population” has been published in JAMA Psychiatry. Editorial in JAMA Psychiatry by Cathryn M Lewis, King’s College London

Katherine L. Musliner

Aarhus BSS, Aarhus University, National Centre for Register-based Research

Mobile: (+45) 5271 4661

Email: klm@econ.au.dk

Esben Agerbo

Aarhus BSS, Aarhus University, National Centre for Register-based Research

Mobile: (+45) 5177 9359

Email: ea@econ.au.dk