Insight provided by a rare genetic form of dwarfism could help researchers come up with breakthrough treatments for bipolar disorder.
In an unlikely connection, research suggests a genetic disorder called Ellis van-Creveld (EvC) protects against bipolar disorder, the University of Massachusetts Medical School reported.
"No one doubts that bipolar affective disorder has an important, disease causing genetic component," said neurologist and geneticist Edward I. Ginns, professor of psychiatry at UMMS and lead author of the study. "In our search for the causes of bipolar affective disorder, this is a paradigm changing discovery that could lead to better treatments."
To make their findings the researchers looked at 40 years-worth of medical data from the Old Order Amish families of Pennsylvania, which has a high rate of both conditions. These two diseases are believed to genetically "travel together."
EvC dwarfism occurs when genetic mutations disrupt the signaling pathway dubbed sonic hedgehog (Shh). A statistical analysis confirmed that Shh also plays a significant role in bipolar disorder.
"Since mutations causing EvC do so by disrupting Shh protein function, linking abnormal Shh signaling to major affective disorders provides a concrete molecular and medical basis for patients' symptoms that should help break down the stigma associated with mental illnesses," Ginns said. "If we can understand more details of the Shh signaling pathway in bipolar disorder, it could dramatically change the way we diagnose and treat these conditions."
The findings suggest drugs already in clinical trials for other conditions that target Shh protein signaling could be used to treat bipolar disorder. Although the team has a good idea of which of these drugs could stop symptoms of bipolar disorder, it is still unclear exactly which changes occur in the Shh pathway that leads to the condition.
"The Shh pathway involves more than a dozen other molecules, and interacts with over 100 other genes. It's likely that other genes or proteins in this pathway may participate in determining the various symptoms and sometimes catastrophic outcomes seen in patients with affective disorders, including suicide," Ginns said.
The study results were published in a recent edition of the journal Nature.
