Michael Eriksen Benros, M.D., Ph.D. is professor and Head of Research at Mental Health Centre Copenhagen, Copenhagen University Hospital, Denmark. He received a two year grant from GLA for his study: Nationwide Cohort Studies Examining Psychiatric Disorders and Suicidal Behavior after Lyme disease.
Why did you want to become a scientist?
As a child, I wanted to be an inventor, and then later on, during high school, I played elite level basketball, and wanted to combine sports and being a medical doctor. I started med school with that in mind, but I also played basketball in med school, in the best Danish league, where there was a sports doctor on the team. I realized it wouldn’t be so fascinating, because most of the time was just spent sitting there. During my medical studies, I became increasingly fascinated by brain disorders – psychiatry and neurological disorders, so I changed my path to being a psychiatrist and neuroscientist. When I look back, I realize I actually combine the things; wanting to be an inventor is like research, and helping people as a medical doctor. In that way, it has all made sense somehow.
Do you have activities or hobbies that have given you creative inspiration for your research? Or any that are simply for fun or relaxation?
I currently enjoy tennis, hockey and running, which are the sports that I can best fit into my professional and family life. I actually enjoy team sports the most. I like to go out into the city and to music festivals when it’s allowed. We have a famous music festival here in Denmark, the Roskilde Festival, about half an hour outside of Copenhagen that we like to go to. I love traveling and exploring other parts of the world, and with research there’s lots of opportunities for travel and meeting people from around the world and collaborating with them. That’s actually how I met Dr. Brian Fallon, at a conference in NYC. (Editor’s note: GLA grantee and Dr. Benros’ research collaborator on their upcoming publication). I had an invited talk about our results utilizing the Danish nationwide health registers, were we can access data on the entire Danish population as one large cohort followed longitudinally for infectious exposures, and subsequent risk for mental disorder outcomes. Brian proposed that we could do a large study on Lyme disease and mental disorders and suicide behaviors. He knew about GLA and how to make an application to it.
Did you have mentors or other scientists who inspired you?
It would be my PhD supervisor, Professor Preben Bo Mortensen at Aarhus University, who inspired me and shared my enthusiasm to study the link between the immune system and infections with mental disorders. He gave me the access to the large scale Danish registries and biobanks, and working with him helped to spark my research career. Professor Merete Nordentoft from University of Copenhagen is another mentor. She’s a psychiatrist who inspired me with her incredible force and will to get things done, and also to have a clinical impact on society with research. She’s working in psychosis research, particularly early intervention studies.
Another thing that inspires my research is working as a clinician, and having patient interactions. It raises a lot of inspiration for research and often initiate clinically relevant hypotheses that we can then investigate as research question on the large-scale Danish data.
Are these nationwide registries used widely in health research in Denmark? How does the public feel about the use of their information?
Access to these registries and their use for research purposes is rapidly expanding. The public appreciates that research is being done. Everything is strictly regulated so you can only work on coded data in secured folders, and in aggregated forms. We’re not allowed, by law, to look at individual people’s data; we can only look at it with at least three people within each column. We haven’t yet had research data breaches and we’re very much aware that it’s a privileged situation, so we have to take care of the public trust to keep having this opportunity, which is ultimately used to help improve the treatment of different disease, and is thus of utmost importance to the public. This information is not shared with insurance companies - it’s strictly for research purposes.
If you were hosting a dinner party, which scientists or doctors, living or dead, would you invite, and why?
The easy answer is to invite Albert Einstein (1879-1955), because he has this mad scientist look and also because he’s considered the greatest researcher of all time, so I’d like to have met him in person. And I would also like to meet Dr. Niels Bohr (1885-1962), a physicist and the most famous Danish researcher, and Dr. Emil Kraepelin (1856-1926), the father of psychiatry, and a researcher from more than 100 years ago. He turned psychiatry to the way we approach it today. He proposed some of the psychiatric categories we still use, including dementia praecox (schizophrenia) that we still use today. He also back then proposed that schizophrenia might be an immunological disease, back in the 1890s or so. At the time, they couldn’t identify the syphilis bacteria, but he noticed the association between the skin symptoms and the brain disorders. Up until antibiotics became readily available after the second world war, it was about one-third of the patients admitted to mental state hospitals that had neurosyphilis, which caused the symptoms.
Another one to invite is Dr. House, the one from TV (Fox drama, 2004-2012). Normally I’m not one to watch medical TV series, but this one is the exception, which I liked during my medical studies. He liked rare diseases, and identified causes for the symptoms. He was a great doctor but a terrible person. But he could probably be entertaining at dinner.
He would shake up your dinner party, but can you imagine him in the presence of these others? Yelling at them or saying something abusive?
It might end up in a fight…a dinner to remember.
If you could work on any scientific question, without worrying about the budget, what would it be?
I would do the research I’m doing now, biological and precision psychiatry, which is the name of my research group, where the focus is to identify the causes of mental disorders, and to identify objective markers for treatment, with a particular focus on immunopsychiatry. This is the intersection of infections, the immune system, and the development of mental disorders. Overall, I’m actually doing what I’d like to do, but if we had more funding, we could do it faster and bigger and better. That’s the issue that we’re limited by - the funding that we can obtain. In Denmark, much of the research funds are externally sourced. So, it’s hard to make a ten-year plan since much of the funding is short term, and you have to constantly get short grants. It would be easier if the institute or state could fund the whole research program.
So, you would continue what you’re doing, and you’d like to make it bigger. But is there a dream project that you could work on for 10 years? What’s the first thing you’d choose?
There are so many things…but my research “baby” is a clinical study of people with first onset depression and psychotic disorders, along with healthy controls. We take the cerebrospinal fluid and blood. Then we do microbiome testing, and extensive cognitive testing with psychopathology and neurological evaluation. We’ve collected from the first 300 patients. This is such unique material, and we should do it for at least 1000 people with longitudinal follow-up, so we can identify the different subgroups and identify the causes of these mental disorders. It’s a very costly study with all the different tests. That’d be the hardest thing to get funding for, but I think it’s important for the future to unravel some of the underlying factors for mental disorders and to come closer to what happens in the brain.
Because it’s prospective, it’s sometimes a hard sell, to tell people that I “might” get data. You need to get somebody who really grasps that impact, and it’s one of the most valuable studies to fund.
And they’re always very expensive, if you want to do them really large-scale.
In psychiatry, is it now pretty much generally accepted that these psychiatric disorders have biological underpinnings?
We work around a biology-psychology-social factors model. Research parses these things out, with a hard focus on biological factors since then we’d have a treatment target. Historically psychiatry was paired with neurology. But in the 1970s, it went toward theories that were not backed by quantitative science, for about 30 years. Psychiatry has thus lagged behind other medical fields that have undergone large developments. From the 1990s to now, it’s returning to a medical research field. We would like to identify the causes of mental disorders, so we can more precisely treat them than we can today. Psychotherapy will still be supplementing the treatment.
You mentioned syphilis earlier. To any psychiatrist, that must raise the possibility that it can’t be the only mental disorder with an infectious cause.
The first Nobel Prize related to psychiatry was for using malaria to treat psychotic symptoms of patients with neurosyphilis. They gave them malaria and then induced the immune system to also fight off the neurosyphilis. But some of them unfortunately died of the treatment, so it was very far from perfect, but it was enough to be awarded the Nobel Prize anyway. (Editor’s note: 1927 Nobel Prize in Medicine to Dr. Julius Wagner-Jauregg.) At that time, neurosyphilis cases were one-third of all patients admitted to state mental health hospitals in Denmark. But when antibiotics were discovered after the second world war, cases of neurosyphilis disappeared from the mental health hospitals. So, antibiotics have also been one of the greatest medical successes in psychiatry. But then people thought it was specific to syphilis. They thought the brain was an immune privileged site, without immune cells there. In the beginning of the 1990s, it was recognized that the blood brain barrier becomes more permeable during infections, and that there are in fact immune cells in the brain called microglia, and a lymphatic system in the brain. We’ve learned a lot in the last 20 years.
And now with Covid-19, immunopsychiatry has become almost mainstream. It’s almost common knowledge that if you have a very severe Covid-19 infection, you can have cognitive sequelae afterwards, and increased risk of anxiety and depression, and that is partly due to the immune system’s effect on the brain. When admitted to the hospital with Covid-19, 34% of patients have delirium and confusion and other psychiatric symptoms, and it’s immune components doing it in many of the cases. I think interest in immunopsychiatry will grow.
Did you ever have a big “aha” moment? What was it, when and where?
Related to research, it’d be when I was a medical student. I was doing an internship with a general practitioner, and we saw two patients - one diagnosed with depression and the other with psychotic disorder. And it turned out that they had undetected cancer: one had brain cancer and the other had small cell lung cancer. That led me into my first research work. I got so fascinated by this that I approached Preben about the nationwide health registries and asked if he was willing to help me investigate these associations with the entire Danish population. We found that when first admitted to a mental health hospital, the first month after, there is a 19-times increased risk of having a brain tumor that was undetected at the time of admission, and a 6-times increased risk of having small cell lung cancer, especially for people greater than 50 years of age. And I think that sparked my research career.
Brain cancer causes pressure on the brain but it could also be an immunological reaction that causes these symptoms. Small cell lung cancer could have paraneoplastic symptoms, where the cancer can have molecular similarities with brain structures. So when the immune system tries to fight it off, some of the antibodies against the cancer can cross-react with the brain and cause neurological and psychiatric symptoms. I started reading more about this, and also the PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) theory, with infections inducing autoimmune responses. It’s both infections and cancer that are the primary causes of autoimmune responses that can affect the brain. That led me to doing a PhD on this topic, which is infections, autoimmune diseases and cancers and clues to the etiology of mental disorders. These “aha” moments led me to the path of research that I have continued on ever since.
Dr. Benros was interviewed by GLA via zoom by Mayla Hsu, Ph.D. The interview has been edited and condensed for clarity.
Director of Science & Research at Global Lyme Alliance