Bipolar disorder is a complex mental health condition that affects an estimated 200 million people worldwide.
While our understanding of depression and mania stretch all the way back to ancient Greece, just how these two stages of bipolar disorder develop and intersect has largely remained a mystery.
But new research published Tuesday in the journal Translational Psychiatry shows how the first-ever bipolar stem cell lines can give us clues as to how brain cells develop in people with bipolar disorder.
Scientists from the University of Michigan Medical School were able to grow brain cells called neurons from the skin cells of bipolar patients and compare them to normal, healthy neurons, as well as test how lithium, the most common bipolar medication, affected those cells.
“This gives us a model that we can use to examine how cells behave as they develop into neurons,” Sue O'Shea, a University of Michigan stem cell specialist, said in a statement. “Already, we see that cells from people with bipolar disorder are different in how often they express certain genes, how they differentiate into neurons, how they communicate, and how they respond to lithium.”
Transforming Skin Cells into Brain Cells
Researchers took cells from skin samples given by bipolar patients and created induced pluripotent stem cells (iPSCs), which are similar to umbilical cord stem cells and can grow into any other type of cell in the body. From there, the researchers were able to coax the cells to develop into neurons.
Under a microscope, the research team noticed differences between bipolar neurons and neurons from the brains of people without a mental disorder.
Researchers found that the bipolar neurons expressed more genes for membrane receptors and ion channels, specifically those that transfer calcium between cells.
Because calcium is crucial to neuron growth and development, the researchers say their findings support the theory that small genetic differences during early brain development are crucial to the onset of bipolar disorder and other mental illnesses.
They also discovered small differences in the cells’ microRNA—which helps to determine which genes are expressed and how—in bipolar patients, supporting the idea that several genetic vulnerabilities are responsible for the development of bipolar disorder.
Fully Customized Treatments on the Horizon
The University of Michigan team also exposed the bipolar neurons to lithium and observed how it altered their calcium signaling. Researchers say this will allow them to study therapies on a patient's individual neurons in a laboratory setting.
With this line of research, the current trial-and-error approach to treating bipolar disorder could be tailored to specific patients and assessed at a microscopic level. It could mean fewer unwanted side effects from medications and quicker identification of effective treatments, the researchers said.
“We're very excited about these findings. But we're only just beginning to understand what we can do with these cells to help answer the many unanswered questions in bipolar disorder's origins and treatment,” Dr. Melvin McInnis, principal investigator at the Heinz C. Prechter Bipolar Research Fund, said in a statement.
The research team is currently building up more stem cell lines from more patients with bipolar disorder, which can take months, and they will share them with other researchers at the university.
Image courtesy of the University of Michigan Pluripotent Stem Cell Research Lab.