Researchers may be one step closer to identifying the genetic cause of bipolar disorder.
A study published in the Journal of the American Medical Association (JAMA) Psychiatry has identified 84 potential inherited gene mutations that could contribute to the most severe forms of bipolar disorder.
“We have known since the 1920s that the illness has a large inherited component to it. But in the last eight years we have uncovered particular genetic variations that play a role in setting bipolar disorder in motion,” Dr. James Potash, chair of psychiatry at the University of Iowa and co-author of the study, told Healthline. “These variations explain some of what is going on, but there is plenty still to discover.”
According to the World Health Organization (WHO), bipolar disorder affects 60 million people worldwide.
The disorder is characterized by “manic and depressive episodes separated by periods of normal mood.”
Manic episodes involve irritable or elevated moods, inflated self-esteem, overactivity, and a decreased need for sleep.
Data from the National Institute of Mental Health shows 2.6 percent, or approximately 5.7 million adults in the United States, are living with bipolar disorder.
Searching for a cause
The exact cause of bipolar disorder is unknown.
However, the Mayo Clinic says several factors may be involved. These include physical changes in the brain, an imbalance of naturally occurring brain chemicals, and inherited traits.
“If someone has bipolar disorder type I, the severe form of the illness, the odds that their child will have it are about 5 to 10 percent. That is 5 to 10 times the rate in the general population,” Potash said.
The study Potash was involved in looked at eight families with a history of bipolar disorder through several generations. The researchers used next-generation sequencing to examine the DNA of 36 of the family members.
“Next-generation sequencing is a way of combing through each of the chemical letters in DNA (called nucleotides) that spell out genes,” Potash explained. “In our study we went through about 50 million of these for each person we looked at. The idea is to look for misspellings that are present in people with bipolar disorder.”
Earlier studies examining the genetic cause of bipolar disorder focused on identifying common DNA changes that could only explain a small percentage of the risk for bipolar disorder.
This latest research, led by Dr. Fernando Goes of the Johns Hopkins University School of Medicine, instead focused on identifying more rare genetic mutations that are less common, but may be linked to the more severe forms of bipolar disorder.
However, the researchers caution that the data is not yet strong enough to show a direct link between a specific mutation and bipolar disorder.
“One thing we learned is that it will take genetic data from at least several thousand more people with bipolar disorder to confirm that these rare mutations do in fact directly cause the disease,” Goes said in a press release. “We are working with the Bipolar Sequencing Consortium to gather more data and collaborators so we can definitively figure out causes.”
New treatments possible
Researchers hope that identifying a genetic cause for bipolar disorder may pave the way for improvements in treatment and diagnosis.
"Many of the pieces of the puzzle of what may cause bipolar disorder are coming together,” Dr. Hilary Blumberg, director of the Mood Disorder Research Program at Yale University, said. “Putting these pieces together will help us to better understand the causes for bipolar disorder, find new ways to detect bipolar disorder earlier, and find new and more targeted treatment strategies.”
Potash is confident that researchers are getting closer to identifying the root cause of bipolar disorder after decades of research.
“Given that we as a field have been working on this problem for 100 years, you’d think we’d have gotten further. But if you realize that the human brain is the single most complex thing in the known universe, then you begin to see why progress has been slow,“ he said.
Advances in research methods and the advent of next-generation sequencing technology means scientists are able to examine DNA more quickly and cost effectively than was possible 10 years ago.
“This is a very exciting time because we have unprecedented tools that we can use to get to the bottom of what is going wrong in the DNA in bipolar disorder,” Potash said. “New treatments should emerge from these new insights. These are much needed as those we have now work for about two-thirds of people, but that leaves a lot of people suffering, and many who do not survive the onslaught of bipolar disorder.”