Presenting maladaptive responses to every day events is debilitating for anyone; unfortunately, that is the typical story for those suffering from neuropsychiatric disorders, such as schizophrenia, depression, or Alzheimer’s disease. Basic and clinical researchers have attempted to understand these maladies from a biological perspective; novel insights into these complex conditions may come from the integration of the data from clinical cases and the data from animal research.
Lucky for us, translational investigators are entering a modern era in which lab based results can be correlated with findings in the field. A great example of this is the Psychiatric Ratings using Intermediate Stratified Markings (PRISM) project*, a European coalition that will correlate blood testing, brain functional imaging, and smartphone apps that track social behavior. PRISM will compare groups of people with different neuropsychiatric disorders to understand which biological factors relate to behaviors that they have in common, such as social withdrawal. This will lead to the understanding of how similar alterations in behavior can emerge from different types of damage and, eventually, to creating preventive markers that lead to earlier interventions.
The coordinator of the PRISM project is Martien Kas, a neuroscientist and Professor of Behavioural Neuroscience at the Groningen Institute for Evolutionary Life Sciences at the University of Groningen. After giving a talk related to his research and the PRISM project at the University of Groningen, Professor Kas sat down with #Neuromexico to answer our questions related to his experience and his future perspectives:
AS: Andrea Soto
MK: Martien Kas
AS: I would like to start by asking about your story and how you became the scientist you are today.
MK: Well, since I was a young kid I was always interested in what determines the way we behave. In college, I went to study Biology and encountered neurobiology and felt wow! This is it! This is giving the answers to my questions. So I went to a master degree mainly in neurobiology, and also ecology and psychopharmacology. Then I moved to Stanford University, where I studied sleeping behavior and circadian rhythmicity in rodents; this was a very inspiring environment that got me thinking into my next project. I wanted to understand the neurobiological mechanisms underlying behavior, for which I did a postdoc in Utrecht were I applied behavioural genetic studies and learned more about neuropsychiatry on the basis of collaborations with clinical colleagues.
AS: Were you always interested in animal models and neuropsychiatric disorders?
MK: Not exactly, I went in to animal models because I wanted to understand the biological basis of human behavior, but as you cannot do direct manipulations of genes or groups of cells in humans, I went to look for an alternative model system. When I started working at the University Medical Center, in Utrecht, I encountered psychiatrist and out of our conversations I realized that behavior is best noticed when it is out of control. So soon those two worlds came together.
AS: Translating research from non-human models to humans is never easy. How do you face this challenge?
MK: It is almost a field in its own to study how to do this better. Most of my research has been based on evolutionary conserved processes. I like to think about essential behavioral strategies and look for mechanisms that have been conserved through evolution and are relevant across multiple species. This makes working towards the translation a little easier.
AS: How do you feel about human studies and what value do you see in them?
MK: Discovering new biological principles for this field of research requires multidisciplinary research with interactions within people from different disciplines and with different ways of thinking. It is only possible to fully tackle the problems I am interested in by using these multiple approaches and having these cross-discipline interactions with other scientists.
AS: Coming from Drosophila research, I feel compelled to ask how do you feel about studies in even simple animal models.
MK: Well, that is actually one of my reasons to move to Groningen. The University here does research on a large variety of species, such as fish and flies, which will allow expanding my view about behavior and conservation. There will be a large potential in mixing the studies that I currently perform with genetic studies in relatively simpler organisms, such as the flies. I believe this will make the process of understanding the basic mechanisms underlying essential behaviors more efficient, even though we must consider that simple organisms might not have the complex phenotypes we see in humans.
AS: Thinking about the PRISM project and the use of smartphone applications to study human behaviour, how did such a project come to be?
MK: It all started when I was having a conversation with a psychiatrist, Jacob Vorstman with whom I have co-developed the app. We realized we were both interested in this dilemma of studying social behavior in humans in a way that could be correlated to the rodent models (and other animal models); our main problem was how to study social behavior in humans in an objective way without making use of questionnaires. We wanted to study human social behavior “in the wild”, in its natural habitat, and monitor this longitudinally. We considered that smartphone activity monitoring would be a good way of getting some proxies of this social behavior; eventually we hope to obtain objective social measures in humans in a way that they are translatable to the studies in rodent. This will hopefully establish an important bridge between the neurobiological knowledge that we obtain in rodents and the gap of knowledge on the etiology of neuropsychiatric disorders.
AS: How did scientists from other nations get involved?
MK: There was a project call from Europe’s Innovative Medicines Initiative (IMI) that allows academic consortia to compete for funding; we proposed investigating quantitative biological measures that would permit a better cluster of patient populations based on biological parameters. Our idea was that Alzheimer’s disease or schizophrenia patients often present social withdraw as an early symptom, even though it is typically neglected in clinical studies. We filled the requirements and presented the phone app as one of the potential measures. Eventually it all came together and the project got extended to biological substrates, cognitive deficits, and the relationship of these with each other and the functional validation of the results with homologous rodent paradigms. More people got involved and the app became one element of a bigger thing.
AS: How did you select the researchers that would be your collaborators?
MK: Luckily the European College of Neuropsycopharmacology (ECNP), of which I am a member of, has several networks consisting of researchers that focus on certain neuroscientific topics. In my case, the group is focusing on studies related to improving medication for neuropsychiatric disorders, such as Major Depression. Within this group a consortium was formed and submitted a grant proposal. Having these networks in place was an important key to success.
AS: What would you like this project to become?
MK: At the end it is about having better treatment options for patients. The community realizes that we will need a paradigm shift and focus on the biological aspects to understand neuropsychiatric disorders and then treat diseases in patient populations that are clustered on the basis of biological homology rather than on diagnosis.
AS: Would a goal be to have every person using this phone app?
MK: Perhaps. The app will hopefully become a tool capable of early detection and classification, especially as social withdrawal is thought to be a very early symptom of several neuropsychiatric disorders. So having a tool for early detection and early treatment monitoring would be ideal. However, this goal requires larger groups of the population, which is still something we are working on. Another goal would be to have the app in patients and to use it to predict relapses of their disease. We are working on both ideas.
AS: Thinking about every person having this app, have you faced the problem of protecting privacy?
MK: Yes, that has been one of the main focus areas. We ended up having extended discussions with experts about it and were ensured we could keep all the data very secure. For example we could have Bluetooth sampling that is encrypted but still let us know if it is directed to the same device or not – even though we do not know the identity of the device or the person carrying it,-, and we would never collect content of any kind. This was, the app, an out-of-the-box scientific, so we are sure it will have quite some interesting positive consequences in the future.
AS: Do you think this project will contribute to making psychiatric diseases more socially acceptable and more of a common topic?
MK: Yes, I think this is already changing and that is very important. Patient-family associations are partners in the project and provide input to scientists. They are very much in favor of this research, especially with the focus on social withdrawal because of the consequences it has on patients and caretaker.
AS: As a final detail, what recommendations do you have for young scientist?
MK: First, to really go for the things that you are motivated by. In any choice you will have to make concessions at some point, so you have to focus on your main idea and major goal. Always follow your heart but use your brain, and use it often. Second, scientists should be capable of explaining the relevance of their work to the general public, such as by telling their story in this blog. For example, we perform animal studies to understand the neurobiology underlying behavioural disorders, but we also keep on explaining to the general audience why this is important. If the society understands why our research matters, they will support it and we will all work together.
AS: And any specifics for scientist from abroad, such as Mexican researchers?
MK: No, just be a scientist. It does not matter where you are from, dare to follow your ideas and remain open to feedback from others.
We thank Martien Kas for his collaboration with this interview. He is working in a fascinating topic aiming to bridge the gap between social science and biological research, which is in the interest of society in general, and also neuroscience as an area that is strongly related to both sides of the coin. We recommend all our readers to check his recent publications and to be attentive to the future results of the PRISM project (http://prism-project.eu/), for sure they will not be disappointing.
*The project leading to this application has received funding from the Innovative Medicines Initiative 2 under grant agreement No 115916. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation program and EFPIA.
Andrea Soto Padilla
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