Give me some skin! I want to make some neurons (Image: Mlenny Photography/Getty Images)

What a nerve! Skin cells taken from people with bipolar disorder have been turned into brain cells. These in turn are offering up clues about the changes in the brain that drive the disorder, and may also provide a way to test new treatments.

About three in every 100 people develop bipolar disorder – a mental illness characterised by episodes of depression and euphoria. But the condition remains poorly understood.

That’s because it would be too invasive to obtain and study viable nerve cells from the brains of people with the condition.


There are also no good animal models, because bipolar disorder – although highly heritable – has, for the most part, not been linked to any specific genes that can be studied using animals.

“People say the condition is probably the result of a lot of small contributions by multiple genes,” says Sue O’Shea at the University of Michigan in Ann Arbor.

Clear differences

Now O’Shea and her colleagues may have found an ethical way to make a genetic model of the condition. First, they took skin samples from 22 people with bipolar disorder and 10 healthy volunteers. They induced these adult skin cells to return to a stem-cell-like state, creating what are called induced pluripotent stem cells (iPSCs) and then encouraged these cells to mature into neurons.

O’Shea was surprised to find that neurons derived from people with bipolar disorder grew differently from those from people without the condition. “I was expecting it would take decades of careful science before we would find any real differences,” she says.

The “bipolar” neurons expressed more genes involved in calcium signalling between cells. Interfering with this cellular communication can disrupt healthy brain activity, and calcium signalling has already been implicated as a likely factor in diseases like bipolar disorder. Treating the cells with lithium – a common treatment for bipolar disorder – reduced the abnormal signalling to normal levels.

Some of the genes which influenced activity of neurons were not previously known to be involved in bipolar disorder. “Some of the genes misdirect neurons to the wrong area in the brain,” says O’Shea.

Right cell, wrong place

This could cause some neurons programmed to become part of one brain region – the cortex, for example – to express genes typical of a different brain region entirely. Such a genetic difference might provide clues as to why certain people are predisposed to developing bipolar disorder in later life, she says. What might trigger the condition is still unclear.

Carrie Bearden at the University of California, Los Angeles, thinks the work is very interesting. She says bipolar disorder may not have been a target of iPSC research before now because the genetics of the condition seem so elusive. “I think that the methodology opens up incredible new avenues for future research,” she says.

“It’s very early days,” says O’Shea, but she hopes that one day the neuronal model could be used to test new therapies for bipolar disorder.

It may even be possible to take skin samples from people with the condition, convert the cells into neurons, and then work out in a dish which therapy or combination of therapies will be most beneficial for each person. At the moment, many people with bipolar disorder must undergo months or years of trial and error experimenting to find a therapy that can improve their condition.

Journal reference: Translational Psychiatry, DOI: 10.1038/tp.2014.12