Genetic profile to predict the risk of heart problems in psychiatric patients

Certain psychotropic drugs increase the risk of prolonged QT interval. Through the use of genetic analysis, a PhD project aims to shed light on who is at particular risk of this.

Marlene Schouby Bentestuen, PhD student, Aarhus University. Photo: Marjun Danielsen, AU Foto

Cardiac side effects from psychotropic drugs are a known phenomenon. PhD student Marlene Schouby Bentestuen from Aarhus University carries out research into the risk of developing long QT syndrome in patients who are treated with psychopharmaceuticals. She states following:

Prolonged QT interval gives an increased risk of arrhythmia, which can cause cardiac arrest, so this is something that we need to be very aware of.

Marlene Schouby Bentestuen is a qualified medical doctor who has been employed at the Department of Cardiology at Kolding Hospital, and has also been a researcher in psychiatry. She has not yet decided which direction she wishes to take, but one thing is certain: with a grant from the Danish Cardiovascular Academy, she aims to make it easier for psychiatrists to risk-assess patients in relation to the development of extended QT interval.

All new drugs must be tested in relation to prolonged QT. According to Marlene Schouby Bentestuen, that means that there is a certain level of confidence in the psychopharmaceuticals that we currently use, but there are still patients who experience this side effect. An article from 2013 estimates that the incidence of experiencing drug-induced long QT syndrome (from non-cardiothoracic medication) is 1 – 10/100,000 (Behr & Roden, European Heart Journal, 2013).

Uncertain why some develop prolonged QT, while others go free

“Long QT syndrome is a bit of a black box. We still do not know exactly why some people get drug-induced long QT and develop arrhythmia, while others do not. So I want to develop a genetic profile that identifies patients who could be at risk of developing prolonged QT when they receive psychotropic drugs,” says Marlene Schouby Bentestuen.

First and foremost, the researcher aims to determine how many Danish patients receive drugs with a risk of developing prolonged QT, and then determine the incidence of cardiac side effects.

Genotypes must be found for patients with prolonged QT

Subsequently, she will analyse the genotypes of patients who are at risk of developing prolonged QT interval due to psychopharmaceuticals. For this purpose, Marlene Schouby Bentestuen will use a database of more than 70,000 patients who have a psychiatric condition and have been treated with psychotropic drugs. The database has been established by the Danish iPSYCH project (iPSYCH was founded in 2012 by the Lundbeck Foundation, and supports research into psychiatry and genetics). She will also use two other biobanks, UK Biobank and Estonian Biobank, which, in contrast to iPSYCH, provide access to ECG data, from which prolonged QT interval can be established.

The analyses should show a pattern in the genotypes that is repeated in all three databases. Furthermore, genotypes already identified in other projects will be investigated:

"By investigating, inter alia, a limited panel of known genetic variants and using a polygenic risk score based on a whole genome analysis for prolonged QT, I aim to identify a risk genotype that appears in patients who are treated with psychopharmaceuticals,” says Marlene Schouby Bentestuen.

She goes on to explain that the goal is then to develop a genetic risk score which can support the clinicians’ choice of medication.

In the future, we will be able to provide personalised medicine on the basis of genotype

“By using genetic data, we can tailor the medical treatment and choose the right medicine with greater confidence right from the start. Switching drugs often leads to long treatment pathways, but with a knowledge of the genotypes that have a particular risk of developing prolonged QT and perhaps also arrhythmia, I hope that we can reduce the cardiac side effects of psychopharmacological drugs,” says Marlene Schouby Bentestuen.

A financial calculation of what a new genetic stratification of patients will cost is also part of her project.

About the project:

  • The PhD project was begun in September 2022 (with a break due to maternity leave at the time of writing)
  • The project will be completed in August 2026
  • The principal supervisor is Assoc. Prof. Christiane Gasse, Department of Clinical Medicine, Department of Affective Disorders and Psychosis Research Unit, Aarhus University & Aarhus University Hospital
  • The project is supported by the Danish Cardiovascular Academy and the Danish Heart Foundation