In search for more efficient treatments for psychiatric disorders with ERC starting grant

Juan Pablo Lopez‘ research aims to understand how the psychedelic compound psilocybin may be used to treat psychiatric disorders. Why people respond differently to antidepressant treatment is one of the questions he’ll try to answer.

Assistant Professor Juan Pablo Lopez, Karolinska Institutet (KI), has been awarded the prestigious European Research Council (ERC) starting grants and receives EUR1.5 million over five years for projects to understand the molecular mechanisms, cellular circuits, and complex behaviours associated with the fast-acting antidepressant effects of psilocybin.

– Our laboratory uses innovative concepts, tools and techniques to understand the molecular mechanisms associated with psychiatric disorders and their treatments. We use animal models (mice) to address psychiatrically-relevant questions such as: Why does one individual respond to a particular antidepressant treatment, whereas another does not? What are the neurobiological mechanisms responsible for the improvement of symptoms? or why do males and females respond differently to antidepressant treatments?

What do you wish to attain?

– Our ERC-funded project, FASTer, aims to understand how fast-acting antidepressants work in the brain in comparison to traditional antidepressants. We are looking to identify the molecular mechanisms, cellular circuits, and complex behaviours associated with the rapid antidepressant effects of psychedelic drugs, such as psilocybin. We believe this project holds tremendous promise for developing new and effective treatments for psychiatric disorders.

Which challenges do you face?

– Unfortunately, there are still significant gaps in our understanding of how antidepressants work in the brain, and this is hindering the development of new treatments for psychiatric disorders. While effective, antidepressants still have significant limitations, particularly a delayed response and low rates of efficacy.

He explains that around 40% of people treated with a given antidepressant will not improve their symptoms, and those who get better might take up to 3 months to experience the positive effects of the medication. This is particularly problematic for a population at elevated risk for suicide.

Fast and sustained antidepressant response

– In addition, the socio-economic costs are great, as mental health psychiatric disorders cost the world economy €2-5 trillion EUR/year and an estimated €600 billion per year in Europe alone. These limitations highlight a major unmet need for the development of fast-acting antidepressant medications that can bring faster relief and reduce the personal and socio-economic burden of depression. Now, there is new evidence from clinical trials suggesting that a single treatment with psychedelic compounds can produce an antidepressant response that is fast (within hours) and sustained (months).

However, many questions remain about the mechanisms of action due to methodological challenges, such as a lack of knowledge of the brain cells and circuits where antidepressant effects take place and limitations of the behavioural tests used to examine antidepressant activity in animal models. Their project FASTer, aims to tackle these issues directly by identifying the brain cells and neuronal circuits responsible for the fast-acting and sustained antidepressant effects of psilocybin.

How does receiving an ERC change the possibility of reaching your goal?

– Receiving an ERC starting grant is amazing for anyone in my position. It is the most competitive research grant available to early career scientists in Europe, so it will not only facilitate the execution of my research goals but also open many doors that might lead to important scientific collaborations in the future. Thanks to this grant, I will be able to expand and further develop a state-of-the-art automatic phenotyping system that is the first of its kind in Sweden. The establishment of this novel equipment will not only be essential for the execution of my ambitious research goals, but it will create opportunities for new research themes that could benefit other key research areas of the thriving neuroscience community at KI, as well as the much larger scientific communities of Stockholm, and Sweden. This ERC grant also allows me to expand my research team and hire qualified and motivated young scientists who share my enthusiasm for neuroscience and mental health research.

What advantages are there of being a researcher at KI and SciLifeLab?

– KI a fantastic place to do science. Not only due to its international reputation but you can easily see this by the number and the high quality of research studies it produces yearly. KI also attracts very good scientific talent, both locally and internationally. I am very impressed with the quality of graduate students at KI. These are very talented and highly motivated young individuals with the common goal of advancing medical research, which is a huge advantage that we have here at KI.

Environment that helps innovative research ideas

Pablo says he’s extremely happy and proud of his lab's students and staff members. The members of his research team come from very diverse backgrounds, both scientifically and culturally, and he thinks these are important ingredients to create a healthy and productive environment to generate and execute innovative research ideas.

– In addition, my laboratory sits at Biomedicum, in Solna, which is an outstanding place for science exchange and collaborations. At Biomedicum we have access to state-of-the-art infrastructure, facilities, and an open environment for interactions across departments and multiple disciplines. Our lab is part of the Department of Neuroscience, but we have close collaborations with groups in the departments of Physiology and Pharmacology, Medical Biochemistry and Biophysics, and Clinical Neuroscience.  We also interact and collaborate closely with labs at SciLifeLab, Stockholm University and KTH.

Which is your favorite spot in Hagastaden?

– I think it is the Wenner-Gren Center. It is where my family and I have called home for the last year and it has been wonderful. The WGC is a fantastic place where scientists from all over the world live. It is located next to the water, Hagaparken, and in close proximity to KI, Stockholm University and KTH. I think Wenner-Gren Foundation is doing a great thing by providing a mechanism that allows international researchers and their families live and settle here in Sweden. They are amazing and don’t get enough credit for a wonderful initiative to host international scientists, so I would love to give them a shout-out and thank you for allowing me and my family to fall in love with Stockholm and Sweden.  

The photo on top of the page is Wenner-Gren Center and the guest researchers' apartments in the half-circle behind.

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