“I took pills for psychotic symptoms, pills for mood swings, and pills for anxiety. Because nothing had ever really given me long-term relief, the doctors were constantly trying me on something new. I went from one antipsychotic medication to another … Nothing. Nothing. Nothing.”
This experience, described by Lori Schiller in her 1996 book The Quiet Room: A Journey Out of the Torment of Madness, is still a common one for people with psychiatric disorders. Because it is not currently possible to know in advance which drugs will work for which people, doctors often need to prescribe different medications on a trial-and-error basis. Some antipsychotic drugs have severe side effects, which often start before the benefits of the drug can be felt; many people therefore choose to stop taking their medication before finding a treatment that works for them [1, 2].
People with different genetic traits can react differently to certain types of drugs [3]. Personalised medicine, in which doctors design tailored treatment plans based on the unique genetic makeup of each individual patient, is already becoming a reality in some fields of medicine, such as cancer and heart disease [4]. Through our research at NORMENT, we want to help move the treatment of neuropsychiatric disorders beyond trial-and-error and into this new era of personalised medicine, whereby we can predict who will benefit from which medications based on their genetic information.
Making brain cells in the lab
Our research focuses on identifying genetic variations that affect how brain cells respond to antipsychotic drugs. In the past, progress towards this goal has been slowed by the unavailability of living human brain tissue for drug response experiments. In our research, we are using an innovative technique that allows us to create brain and nerve cell types from skin cells [5, 6]. This means that instead of using living human brain tissue we can use small skin biopsies donated by people with psychiatric disorders to study how their genes affect their response to different types of antipsychotic drugs.
Predicting treatment response
Ultimately, we aim to design a simple laboratory test that will allow doctors to confidently select the right medication for each person they treat. Such a test would have the potential to help more people with psychiatric disorders find relief from their symptoms much more quickly and with fewer side effects. Our research will also aid in the rational design of the next generation of antipsychotic drugs, based on a better understanding of how to precisely target the molecular causes of psychiatric disorders with fewer off-target side effects.
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References
- Saha, S., et al., Arch Gen Psychiat 64, 1123 (2007).
- Lieberman, J. A. et al. New Engl J Medicine 353, 1209–1223 (2005).
- Lally, J., et al., Pharmacogenomics Personalized Medicine Volume 9, 117–129 (2016).
- Wheeler, H. E., et al., Nat Rev Genet 14, 23–34 (2013).
- Brennand, K. J. et al., Nature 473, 221–225 (2011).
- Assis, D. R. de et al., Cells 10, 209 (2021).
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