New research shows that patients who have had contact with the hospital due to serious glandular disease have a greater risk of subsequently developing depression. The study from iPSYCH is the largest yet to show a correlation between glandular fever and depression.

2021.05.03 | Helle Horskjær Hansen

"It’s interesting that the Covid-19 pandemic has resulted in a renewed focus on mononucleosis infection because the Covid-19 infection appears able to cause similar symptoms with long-term fatigue and an increased risk of subsequent psychiatric diagnoses. The causes behind this are something we ought need to study in more detail in order to gain knowledge about similarities and differences in relation to long-term Covid-symptoms, which could possibly be used in preventative measures," explains Michael Eriksen Benrós.

The vast majority of Danes have had glandular fever – also called mononucleosis – before adulthood. And for the vast majority of them, the disease can be cured at home with throat lozenges and a little extra care. But for some, the disease is so serious that they need to visit the hospital. 

A new research result now shows that precisely those patients who have been in contact with the hospital in connection with their illness, have a greater risk of suffering a depression later. 

"Our study shows that it is associated with a forty per cent greater relative risk of developing depression, if the patient has been in contact with a hospital due to glandular fever," says Professor and Research Director Michael Eriksen Benrós from the Mental Health Centre, Copenhagen, the University of Copenhagen and Aarhus University, who is behind the study.

Demonstrates a correlation

The risk was considerable for up to four years after the infection. 

"It is well-known that mononucleosis infection can cause long-term fatigue afterwards, and we can now see that there is also an increased risk of developing actual depression, which requires contact with the hospital. Fortunately, this was only the case for 1 out of 35 with mononucleosis infection within the study's follow-up, he says. 

The study is a register-based study which has followed 1,440,590 Danes, of whom 12,510 had contact with the hospital due to glandular fever, and of these, 358 – corresponding to three per cent – subsequently developed depression that required hospital contact. 

"Previous studies of the correlation between glandular fever and subsequent depression have primarily been small studies and the correlation has therefore been unclear. This study is the first major study able to demonstrate the correlation with a subsequent risk of depression with great statistical strength," says the lead author of the study, Nina Vindegaard from the Mental Health Centre, Copenhagen.

Affects young people

Glandular fever affects young people aged 10-25 years in particular, and symptoms include fatigue, pain in the neck, fever and swollen lymph nodes on the neck, often accompanied by fatigue in the months following. It is also often young people who come into contact with the hospital because their symptoms are serious.

"This knowledge is important – both for the patient and their parents, but also to a great extent for general practitioners – as there is an increased risk of depression after the infection," explains Nina Vindegaard.  

According to Michael Eriksen Benrós, part of the explanation for the increased risk may be that the brain is affected by the infection:

"We know that mononucleosis infection can lead to long-term fatigue, but the actual underlying mechanisms for how this happens to a greater extent for this particular infection compared to many other infections haven’t been identified. The general hypotheses are that it happens through activation of the immune system, which may also lie behind the increased risk of depression," he says.  

Background for the results

• The register-based study followed 1.44 million Danes born between 1977-2005, with 12,510 of these having had contact with the hospital contact with mononucleosis. Mononucleosis infection was associated with a forty percent increased relative risk of subsequently developing depression. Relative risk is the risk of an undesired outcome in the treatment group divided by the same risk in the control group.
• The study was carried out in collaboration between Associate Professor Liselotte Petersen, The National Centre for Register-based Research, Aarhus University, Professor Søren Dalsgaard, The National Centre for Register-based Research, Aarhus University and Consultant Bodil Lyng-Rasmussen, The Department of Child and Adolescent Psychiatry, Aalborg University Hospital.
• The study is financed by the Lundbeck Foundation.
• The scientific article can be read in Brain, Behavior, and Immunity.

Contact

Professor, Research Director, MD, PhD, Michael Eriksen Benrós
Mental Health Centre Copenhagen, Copenhagen University Hospital
University of Copenhagen
and Aarhus University. 
Direct tel.: (+45) 2625 5239
benros@dadlnet.dk

Nina Vindegaard
MD, PhD student
Mental Health Centre Copenhagen, Mental Health Services, The Capital Region of Denmark
Direct tel.: (+45) 6014 5396

nina.soerensen.03@regionh.dk