About 5.7 million U.S. individuals have bipolar disorder, also known as manic depression illness, according to the National Institute of Mental Health (NIMH). Other sources, including the National Alliance for the Mentally Ill (NAMI), estimate the number at closer to 10 million people with varying levels of the mental illness.

It most often strikes in late adolescence or early adulthood but can also affect children at an earlier age. While treatments exist to level out the mania and depression mood swings, they are not without side effects. And for many people, the greatest challenge is taking their medications when feeling especially good.

A team of Indiana University School of Medicine researchers, led by Dr. Alexander B. Niculescu III, has created the first comprehensive map of genes most likely involved in the illness. Their findings were published in the Nov. 21 “American Journal of Medical Genetics.”

The disorder runs in families and is considered more genetic than schizophrenia, major depression or other mental illnesses. Some research shows if you have a parent or sibling with bipolar disorder, you have a 10 percent to 15 percent greater likelihood of developing the illness.

“There's been a lot of good work in terms of the genetics of bipolar disorder,” Niculescu said. “The problem has been a lot of findings to date were not replicated in other studies. There was a lot of skepticism that the initial findings were not reproduced.”

His team took the data from other studies that looked for genetic associations of bipolar disorder in tens of thousands of people. The team identified and mapped the genes with the highest levels of activity associated with the illness.

In essence, they looked at “gene expression.” The process is similar to doing a Web search, he said.

“The more links there are to a page on the Internet, the more likely it is to come up at the top of your search list,” he explained. “The more experimental lines of evidence for a gene, the higher it comes up on your priority list of genes involved in the disorder.”

Previous thinking was that only a handful of genes were involved in bipolar disorder, “but we're realizing that in bipolar, and also in schizophrenia and autism, there are many, many genes involved — likely hundreds, possibly more than 1,000 genes.

“Bipolar has to do with energy, how active cells are,” he said, noting they found high-energy cells were associated with mania and the less-active cells were associated with depression.

The realization that hundreds of genes are involved in bipolar disorder means researchers have much more work to do to make practical applications for treatment or prevention.

“But it's always better to deal with truth and reality. That's progress,” said Niculescu, who is a practicing psychiatrist, molecular geneticist and assistant professor of psychiatry and medical neuroscience at IU School of Medicine in Indianapolis.

“Not all genetic mutations will occur in every individual with bipolar disorder,” he noted. “Different individuals will have different combinations of genetic mutations.” That explains why past attempts to identify genes involved in the disorder have been so difficult.

“But we can test adult patients and come up with genetic risk based on combinations (of genes) we've looked at,” he said. “The main impact would be prevention — to test people early on.”

Those at risk could take advantage of counseling, lifestyle changes or not-yet-developed strategies to minimize or “derail” the illness.

Other research under way at IU is working on a blood test for mood disorders and already shows promise for identifying day-to-day changes in the blood that correlate with mood.

“Those types of blood markers are going to be very useful in tailoring and personalizing treatment,” Niculescu said.

A a genetic risk score, which Niculescu and his team hope to develop, would be another tool.

Testing asymptomatic people for risk factors is not without ethical challenges, he says, noting science can be used to prevent illness or used for financial gain, such as when an insurance company disqualifies someone based on knowledge of a disease risk factor.

“It's more up to society as to how they will use the information,” he said.

NIMH is funneling more money toward research of mental illnesses. IU has received $1.2 million in a four-year grant to study the genetics of bipolar disorder, which Carriage House executive director Andy Wilson applauds.

Carriage House, 3327 Lake Ave., is a nonresidential clubhouse that offers social support, job-skills training and community-integration assistance for people with serious mental illness.

“A decade ago, the most common mental illness found among the population served by the clubhouse model was schizophrenia,” Wilson said.

“Now we're seeing more bipolar disorder. I think that maybe up to 50 percent of our members have bipolar (disorder). My wife is a child therapist, and she is seeing more and more of it, too. But identifying someone early who is at risk of the illness only does someone good if there is effective treatment,” he said.

Niculescu said the landmark work he and his team have done on bipolar disorder is just the beginning.

“It doesn't mean there's not a lot more work to be done, but at least we've mapped the territory,” he said. “We are finally getting the touchdown after a very, very long drive down the field. This is not the end of the game. We're basically at halftime.”