A bipolar (affective) disorder is characterised by recurrent depressive, manic, hypomanic or mixed episodes. So far, only very limited amounts of neuronal tissue have been available for studies on the progression of this disorder. In order to examine how it such disorders arise, the scientists took skin biopsies from patients and from unaffected control individuals, transformed the skin cells into induced pluripotent stem cells and then generated neurons from them.

First the researchers studied the genetic profile of the generated stem cells to compare the patients’ material with that of the non-affected probands. They then examined the genetic profiles of the nerve cells. Subsequently they compared the behaviour of the nerve cells with regard to their communication with one other and their response to lithium, an active agent commonly used for treating bipolar disorders. They were able to demonstrate specific differences. The researchers were also able to pinpoint how often certain genes were transcribed during the development of nerve cells and in what manner the patients’ cells were transformed into nerve cells.

The researchers found that although there were hardly any differences in the gene expression of iPS cells themselves between patients and non-patients, the patients’ neurons did express more genes particularly relevant to membrane receptors and ion channels responsible for the transmission and reception of calcium signals between cells. Calcium signals are known to play a major role in the development of nerve cells and their functions. When the scientists treated the cells from bipolar patients with lithium, the cells displayed striking changes in calcium passage.

Previous studies showed that bipolar disorder problems had to do with the neuronal calcium balance, according to Paul Latimer from the Canadian Okanagan Clinical Trials in Kelowna, British Columbia. When lithium was present the patients’ cells showed changes in signal pattern, with the lithium not able to normalise calcium signalling, but to alter it remarkably, thus demonstrating the effect the standard therapeutic agent lithium has on calcium metabolism.

The neurons thus produced can be used for more specific drug testing than previously possible. On the basis of such a specific profile, personalised medicine could help those patients who cannot successfully be treated with standard medication.

The researchers have published their work in the journal Translational Psychiatry.

HM Chen, CJ DeLong, M Bame, I Rajapakse, TJ Herron, MG McInnis & KS O'Shea (2014): Transcripts Involved in calcium signaling and telencephalic neuronal fate are altered in induced pluripotent stem cells from bipolar disorder patients. Transl Psychiatry 4, E375. doi: 10.1038/tp.2014.12

Sources: http://www.uofmhealth.org/news/archive/201403/first-stem-cell-study-bipolar-disorder-yields-promising
Paul Latimer: Stem cell research cure source for bipolar disorder. http://www.kelownacapnews.com/opinion/262794361.html