Yes, Bipolar Disorder Does Have a Genetic Basis

A recent discovery, the result of forty years of research among the Amish, has found a missing biological explanation for bipolar disorder and promises that certain drugs already being tested for other illnesses may prove to be blockbuster treatments, perhaps even cures, for bipolar disorder.

Certainly, many factors contribute to bipolar disorder, but the search for a specific biological or genetic basis has been elusive. “This is a paradigm-changing discovery that could lead to better treatments,” said Dr. Edward I. Ginns, M.D., Ph.D., a neurologist and geneticist, and the lead author of the study.

Amish families in Pennsylvania are an ethnically closed population with common environmental factors — a perfect group for a study of genetic influences. The study found that among one family in the Amish community, there was a 15-20% incidence of bipolar disorder, much higher than the 2% typically cited for Americans in general.

More intriguing?

The family also had a higher than usual incidence of a rare genetically caused form of dwarfism.

Downright Fascinating?

None of the family members who have dwarfism also have bipolar disorder!

It’s just like Mendel and his peas! (From high school science class. Remember?)

Janice A Egeland, a co-author of the study, discovered that the genetic mutations that caused dwarfism were, in fact, preventing bipolar disorder. “If something shuts off the disease, it must be the right pathway,” said Ginns. Therefore, he concluded, there is “a concrete molecular and medical basis for patients’ symptoms that should help break down the stigma associated with mental illness.”

He went on to say, “If we can understand more details of the… signaling pathway in bipolar disorder, it could dramatically change the way we diagnose and treat these conditions.”

I just love his analogy, comparing bipolar disorder to a river overflowing and creating a waterfall. “If you want to cut off the flow of water, you will be more successful if you cut it off high upriver from the falls. Current medications work at the low end, close to the falls. This may work from higher up.”

When I read the article to my wonderfully supportive husband, he joked that current treatments work after the water is halfway down the falls. I replied that they’re like sandbags at the front doors of the homes below the falls. And that benzodiazepines are like sump pumps.

It appears that certain drugs already undergoing FDA compliance studies for other disorders may be effective against bipolar disorder by affecting this signaling pathway.

And there is room for more refined discovery and treatments: “The… pathway involves more than a dozen other molecules and interacts with over 100 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.” However, Ginns continued, “Even though the symptoms of bipolar affective disorder can be quite varied and complicated, the underlying genetics might actually have a more simple cause than we could have imagined.”

Published in Nature, Molecular Psychiatry, 10/2014.

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