One in four psychiatric patients in Denmark are readmitted and that carries major personal and societal costs. But can we predict who will be readmitted, while others return to everyday life without symptoms? That is exactly what Professor Kamilla Miskowiak aims to support through her latest research.
She is a professor of cognitive neuropsychiatry at the Department of Clinical Medicine at the University of Copenhagen, and in a new study she and her colleagues examined people with major depressive disorder or bipolar disorder and identified clear neurological and behavioural patterns that may help reveal who is at particular risk of readmission.
“Our study suggests that the brain’s reaction to emotional stimuli may be an important piece of the puzzle when trying to understand who is at risk of a deterioration in their illness. And it may help guide future treatment,” says Kamilla Miskowiak.
In the first part of the study, 112 participants with depression or bipolar disorder were put in an fMRI scanner while being shown images of happy or fearful faces. The researchers then measured activity in the amygdala – the brain’s “alarm button”, which alerts us to danger.
The second part of the study took place outside the scanner. Here, participants were shown faces expressing different emotions – fear, happiness, sadness, anger, surprise, and disgust – and the researchers recorded how quickly they identified each one.
In both cases, it was clear that some people reacted more strongly to negative emotions than others.
The researchers then followed participants over the course of a year and found a link between emotional reactivity and risk of hospitalisation. Participants with a strong amygdala response to fearful faces had a significantly higher risk of being admitted.
Those who identified negative emotions more quickly than positive ones also were at higher risk of admission. In both cases, this applied to people with depression as well as bipolar disorder.
“So this is a vulnerability marker that cuts across diagnoses, and it suggests that we have found broader neurological changes in people with affective disorders,” says Kamilla Miskowiak.
In other words, participants’ brains had a negativity bias and misinterpreted signals in the environment that were not actually threatening. For each small increase in the brain’s response to fear, the risk of hospitalisation rose by 17%.
“Psychiatric disorders such as depression can feel like invisible illnesses, and some people may feel it is their own fault or are told to simply pull themselves together. But we can actually see that there is a real neurological vulnerability. The good thing is that we can then treat this vulnerability,” says Kamilla Miskowiak.
Depression costs Danish society almost DKK 10 billion annually in treatment, care and medication, and DKK 25 billion in lost productivity, according to figures from the Danish Health Authority from 2022. That same year, there were more than 58,000 psychiatric hospitalisations in Denmark, and a quarter of patients were readmitted within 30 days, according to Local Government Denmark. So there is a strong need to identify who requires extra support.
Although MRI scanning is expensive and unlikely to be used for routine assessment of all patients with depression or bipolar disorder, it is easy to carry out a simple test of people’s reactions to facial expressions – one that does not require a brain scanner. The researchers are already developing an online tool that will make it easy for clinicians to administer and interpret the test.
“Of course, it needs to be used alongside an assessment of other factors in someone’s life, such as previous hospitalisations. But it may be a way to screen for who is at increased risk,” says Kamilla Miskowiak.
We still do not fully understand what happens in the brain when some people develop mental disorders. That is why Kamilla Miskowiak and her team work to identify so‑called biomarkers – measurable signs that something is beginning to go awry.
“At the GP, you can have a throat swab to see whether an infection is caused by a virus or bacteria and get the right treatment. But in psychiatry we lack that kind of biomarker. So, if this finding can become a biomarker that predicts prognosis, it would be hugely important,” she says.
Neuropsychopharmacology
Amygdala reactivity to threat, negative facial perception, and risk of future psychiatric hospitalizations: a longitudinal study in major depressive and bipolar disorders
15-Dec-2025
Competing interests KWM has served as consultant for Janssen, and Angelini. BO states that part of his salary while working on this project was covered by a grant from Novo Nordisk A/S. HLK has served as a consultant for Lundbeck. VHD has served as lecturer for H. Lundbeck. GMK has served as consultant for Sanos, Onsero, Pangea Botanica, Gilgamesh, and Seaport, and additionally served as lecturer for Abbvie, Angelini and H. Lundbeck. LVK has within the last three years served as a consultant for Lundbeck and Teva. VGF has served as consultant for Sage therapeutics, and additionally as lecturer for H. Lundbeck, Janssen-Cilag, and Gedeon Richter. All other authors declare no conflict of interest.