A New Way to Study Bipolar Disorder

Article: Transcripts involved in calcium signaling and telencephalic neuronal fate are altered in induced pluripotent stem cells from bipolar disorder patients. (Chen, et al. 2014)

            Bipolar disorder is a serious mood disorder that, according to the World Health Organization, is one of the top causes of lifelong disability. Being such a serious disease means that there is a lot of research going into how it works and how to treat it. However, it is very challenging to study a disease when there is not easy access to tissues to study the physical and chemical aspects of the disease closely. In their paper published in Nature Translational Psychiatry earlier this year, Chen et al. has introduced a potential solution to this problem: induced pluripotent stem cells derived from Bipolar patients. Because many previous studies had shown that Bipolar is a strongly genetic disease, and that certain traits, such as alterations to the regulation of calcium channels, are widely observed in bipolar, the authors decided that it would be worthwhile to try and develop a developmental model of bipolar using induced pluripotent stem cells (iPSCs) which would allow the authors to study living nerve tissue, something that is not possible currently due to the lack of viable brain tissue from people with bipolar disorder.

            The authors used skin samples from six individuals, three of whom had been diagnosed with Bipolar I disorder, and three who had not, and grew those cells until they could be induced into a pluripotent state. After doing so, the authors generated neurons from these stem cells, differentiated them, and then performed a series of experiments on them. Transcription analysis showed that controls and bipolar iPSCs did not have significantly different transcriptomes, but after differentiation, bipolar neurons expressed a significantly different transcriptome from the controls, expressing lower levels of several HOX genes, as well as significantly higher levels of several genes associated with circadian rhythm, namely TIPIN, PENK, and TAC1. These are just a selection of their results, as there was also work done using lithium on the neurons and on the iPSCs caused a number of changes, namely in calcium signaling and in the developmental fate of the cell (lithium acts as a dorsalizing agent). All told, the authors provide significant evidence that they could successfully create neural cell lines from bipolar patients that have great potential as experimental systems for understanding the molecular and genetic basis of the disease, and this allows for further studies to be done, potential on patients with other forms of bipolar disorder, as well as other mental disorders.