Sencan Solay Unal, M.D., likes to observe children with bipolar disorder in a room designed to make them feel comfortable.

Bipolar disorder is a devastating disease affecting more than 2 million American adults. But little is known about the condition in children, particularly which treatments might be safe and effective for their developing brains. A Mayo Clinic psychiatrist has started a ground-breaking clinical trial that may well provide answers.

Dr. Sencan Solay Unal, M.D., is testing the effectiveness and safety of omega-3 fatty acids, the main ingredients of fish oil, to treat bipolar disorder, or severe mood swings, in children aged 12 to 17. Typically, adults with bipolar disorder are treated with mood-stabilizing drugs such as lithium. But for younger patients, those treatments pose significant risks and can be ineffective. “That is why omega-3 fatty acid is so appealing. The side effects are very mild,” Dr. Unal says. “If we had a treatment option like that, and could intervene in the progression of the illness early on, that would be an important milestone in child psychiatry.”

The Mayo study is the first of its kind, involving 32 patients with bipolar disorder and an equal-sized control group. Participants will be randomly selected to receive omega-3 fatty acid or a placebo. Dr. Unal is collaborating with radiology researchers John Port, M.D., Ph.D., and Joel Felmlee, Ph.D., and with brain pharmacologist Elliott Richelson, M.D., to determine the biological basis of pediatric bipolar disorder. They are using novel brain imaging techniques to examine the treatment’s effects on the brain metabolism of children with bipolar disorder.

“This is a disorder that is poorly understood,” says Dr. Lloyd A. Wells, M.D., Ph.D., a child psychiatrist at Mayo. “The fact that anybody is systematically looking at treatment is important in and of itself.” But the biological data, he adds, also will “lead people to understand the disorder more accurately.”

Bipolar disorder is a very complex disease. Although its precise cause isn’t known, scientists believe that the signaling pathways in patients’ brains – “the mailbox, if you will, receiving and delivering the messages to cells”– may be overactive, Dr. Unal says. Mood-stabilizing drugs such as lithium appear to inhibit these overactive mechanisms. So does omega-3 fatty acid, according to recent biochemical studies.

Mayo is one of the few facilities in the world with the expertise to undertake a clinical study for pediatric bipolar disorder. Protocols for research involving children are rightly strict. But Dr. Unal says she has a large pool of potential study participants because hospitals nationwide refer children to Mayo’s Pediatric Mood Disorder Research Program, which she heads.

Widely considered a disease of early adulthood, bipolar disorder can affect patients for a decade before it is diagnosed, resulting in more complicated medical interventions and a generally worse prognosis. Children with this illness suffer severe and long-lasting episodes and are at risk of substance abuse and suicide.

“It is so painful for the children to go through these extreme emotional states that nobody else can understand,” Dr. Unal says. “There is a significant need for studies identifying the developmentally sensitive targets for novel medications for this disabling illness. My hope is that early detection and treatment of pediatric bipolar disorder will result in a better prognosis and functional outcome in adult life.”

—Barbara Toman, September 2008