It is unclear what causes bipolar disorder – a condition characterized by dramatic changes in mood. But researchers from the University of Michigan Medical School have created the first stem cell model for bipolar disorder, which they say could uncover the origins of the condition and open the door to new treatments.

The research team recently published their study in the journal Translational Psychiatry.

To reach their findings, the investigators obtained skin samples from people with bipolar disorder, alongside skin samples from individuals without the condition.

By exposing small samples of skin cells to carefully controlled conditions, the researchers turned them into induced pluripotent stem cells (iPSCs). These are stem cells that have the potential to be turned into any other type of cell. The team then turned the iPSCs into neurons.

They measured gene expression of the iPSCs and then re-evaluated gene expression once the stem cells became neurons.

From this, the team found significant differences between the stem cells taken from bipolar patients and those taken from individuals without the condition.

Bipolar patients ‘express more genes for calcium signaling’

Stem cell lines
The stem cell lines were made from the skin of bipolar patients.
Image credit: University of Michigan Medical School

The researchers found that the neurons from bipolar patients expressed more genes for membrane receptors and ion channels than the neurons from non-bipolar patients – particularly genes for receptors and channels involved in sending and receiving calcium signals between cells.

Since calcium signals play a significant role in neuron development and function, the investigators say their findings suggest that genetic differences in early brain development may contribute to the development of bipolar and other mental health conditions later in life.

When the researchers exposed the neurons to lithium – a chemical that bipolar patients often use to regulate their mood – signaling patterns changed.

The researchers explain that lithium changes how calcium signals are sent and received, so these new cell lines will allow them to determine the mechanisms behind this in cells specific to bipolar patients.

The team also found that the neurons from bipolar patients were “addressed” differently during development than those from non-bipolar patients, meaning signaling could be misdirected. They say this could affect brain development.

Furthermore, the researchers found differences in microRNA expression – small RNA fragments that play an important role in “reading” genes – in the cells of bipolar patients. The teams says this discovery supports the idea that bipolar disorder develops from a “combination of genetic vulnerabilities.”

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