March 30, 2016 7:00 AM

How Research Brightens the Bipolar Disorder Outlook

Researchers seek to understand why bipolar disorder happens, how to treat it more effectively, and how to help patients and their families get the most out of modern knowledge about the condition once known as manic depression.

For people with bipolar disorder, the world can alternate between being a dark, depressed place, and one of infinite possibilities and manic energy.

The roller coaster of moods seems to cascade out of control, unless individuals get help from trained mental health specialists and find a medication that works for them.

Even with help available, far too many people with bipolar disorder end their own lives.

Researchers such as the University of Michigan’s Melvin McInnis, M.D., want to understand why bipolar disorder happens, how to treat it more effectively, and how to help patients and their families get the most out of modern knowledge about the condition once known as manic depression.

McInnis and his colleagues in Taiwan just published a study that could help many patients, and their care teams, stay the course on treatment and avoid suicide.

Meanwhile, back in Michigan, he’s part of a team collecting and analyzing information about hundreds of people with and without bipolar disorder who have volunteered to let U-M researchers study them. The team has even used stem cell technology to observe how brain cells react to bipolar medicines.

Soon, such work will be featured on PBS stations nationwide in a documentary about bipolar disorder called Ride the Tiger: A Guide Through the Bipolar Brain, produced by Detroit Public TV. The documentary airs nationwide April 13.

The one-hour film focuses on the toll the disease takes and the many mysteries that still surround the disorder. But the film also celebrates the achievements of people who have succeeded despite the disease — and of scientists working to understand and defeat it.

For McInnis, every day is World Bipolar Day, not just the official March 30 observance.

"This study shows that even short-term exposure to any of these three mood stabilizers reduces the risk of suicide, suicide death and all-cause death."
Melvin McInnis, M.D.

Stopping bipolar suicide through research

To figure out how to reduce the toll of suicide, first it’s important to understand what factors put people with bipolar disorder most at risk of trying or completing an attempt on their own life.

McInnis and his Taiwanese colleagues turned to a rich source of data to find out: the Taiwan National Health Insurance program database. Asian countries have a higher rate of suicide in general than the United States, but research has lagged behind on prevention. So the question is especially urgent there.

The team looked at anonymous data on the doctor visits, diagnoses, causes of death and prescription records of every Taiwanese adult diagnosed with bipolar disorder between 2000 and 2005.

They followed up with them through 2009, giving a long-term view of what happened after their diagnosis. They zeroed in on those who attempted or completed a suicide, and compared their prescription-filling patterns with those of people with bipolar disorder who hadn’t tried suicide by the end of the study period. They especially looked at mood-stabilizer drug prescriptions in the 30 days before a suicide attempt or before the end of the study.

The findings were clear. The risk of suicide was far lower among those who were taking mood-stabilizing medications compared with those who hadn’t refilled their prescriptions in the last 30 days or didn’t have a prescription at all.

The effect was seen even after taking into account age, gender, and other physical and mental health conditions and medications. Death from any cause was also higher among those who weren’t on mood-stabilizing medications.

It didn’t matter what mood-stabilizing medication they were prescribed, either. Lithium, divalproex and carbamazepine were all associated with a much lower risk of suicidal acts and deaths from suicide or other causes.

“This study shows that even short-term exposure to any of these three mood stabilizers reduces the risk of suicide, suicide death and all-cause death,” says McInnis. “This supports the immediate use of these medications after diagnosis to help patients get the protective effect against suicidal behavior.”

Riding the tiger

Mining troves of data like the Taiwanese records can yield important findings about bipolar disorder on a large scale. But McInnis and colleagues, led by U-M cell biologist Sue O’Shea, Ph.D., are also looking at the condition on the microscopic scale.

That work led the producers of Ride the Tiger to them. Two years ago, the researchers published the first findings from their effort to look at bipolar disorder in a Petri dish. They started with skin samples from people with and without bipolar disorder who had volunteered for a project at U-M funded by the Heinz Prechter Bipolar Research Fund.

By carefully treating those skin cells with certain agents and growing them under controlled conditions, the researchers got the cells to become stem cells — capable of growing into other types of cells. More careful work got those cells to grow into the type of cells found in the brain.

Doing so lets the scientists study how those cells react to medications, how they develop and organize, what genes are more or less active in cells derived from people with bipolar disorder, and more.

Recently, the team published an overview of its work, and the work of others in the field. They’re working to connect long-term information about participants in the study with information about how the stem cell-derived neurons grown from their skin behave.

They’re also seeking more people to join the effort as research volunteers, whether or not they have bipolar disorder themselves. The team hopes the new PBS documentary will help more patients — and those who love them — understand the power and hope that come with research.