While we have used lithium for the treatment of bipolar disorder for decades, we still don’t know exactly how it works. Furthermore, why is lithium so effective in some patients and not in others?
To better understand the beneficial effects of lithium, Andrew Nierenberg, MD, Director of the Dauten Family Center for Bipolar Treatment Innovation at Mass General Hospital is collaborating with Paola Arlotta, PhD from the Harvard Stem Cell Institute. This project will focus on brain organoids derived from patients with bipolar disorder, and, using this approach, Niernberg’s team hopes to better understand the effects of lithium at the molecular, cellular, and functional levels.
Brain organoids are miniature three-dimensional tissue cultures derived from human pluripotent stem cells that, under well-defined cell culture conditions, can be induced to organize into structures resembling various regions of the human brain. In contrast to traditional cell cultures or cell lines that consist of one type of cell, organoids are, as the name implies, more like organs and contain multiple types of cells, including different types of neurons, interneurons and glial cells.
Given the complexity of brain organoids, they represent a promising in vitro avenue for advancing our understanding of brain development and function, with the potential to improve our understanding of the interplay between genetic and environmental factors in the evolution of complex neuropsychiatric disorders and to guide the development of more targeted and effective treatments.
In this study, Nierenberg’s team will take blood samples from patients who unequivocally responded or did not respond to lithium. Then Paola Arlotta’s team will convert those blood cells into pluripotent cells, which in turn can be made into brain cells and then brain organoids. By exposing the brain organoids to lithium, the research team will be able to study how lithium works. What physiologic changes take place in the organoids? What genes are expressed? What proteins are made?
This information will help us to better understand how and why lithium works as a mood stabilizer for some, although not all, individuals.
By gaining a better understanding of how lithium works, we may be better able to individualize and optimize treatment by identifying those who are most likely to benefit from treatment with lithium. In addition, having a more precise understanding of how lithium works may help us to generate new and effective treatments for patients with bipolar disorder.
To learn more about this study, you can visit the Mass General Brigham Rally website HERE.
Read More
Reproducible, miniature 3D models of human brain tissue open new frontiers in neuroscience (Harvard Gazette)
Cable J, Arlotta P, Parker KK, Hughes AJ, Goodwin K, Mummery CL, Kamm RD, Engle SJ, Tagle DA, Boj SF, Stanton AE, Morishita Y, Kemp ML, Norfleet DA, May EE, Lu A, Bashir R, Feinberg AW, Hull SM, Gonzalez AL, Blatchley MR, Montserrat Pulido N, Morizane R, McDevitt TC, Mishra D, Mulero-Russe A. Engineering multicellular living systems-a Keystone Symposia report. Ann N Y Acad Sci. 2022 Dec;1518(1):183-195.
Andrew Nierenberg, MD holds the Thomas P. Hackett, MD, Endowed Chair in Psychiatry at Massachusetts General and is the Director of the Dauten Family Center for Bipolar Treatment Innovation, Associate Director of the Depression Clinical and Research Program, and Co-Director of Center for Clinical Research Education, Division of Clinical Research at the Mass General Research Institute. Dr. Nierenberg is a professor of psychiatry at Harvard Medical School.
