The Thinkers: She peers into the brain for cause of bipolar disorder

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Mary Phillips peers into the brains of people with bipolar disorder, and what she has found there gives a whole new meaning to the term "bipolar."

Dr. Phillips, a University of Pittsburgh psychiatrist, has discovered that each half of a bipolar patient's brain may be responsible for a different extreme of the illness.

Bipolar patients often cycle between periods of paralyzing depression and hyperactive mania.

Using a brain imaging technique that shows the connections between different parts of the brain, Dr. Phillips' group has shown that wiring problems in the left half of the brain may cause patients' manic phases, while a different kind of wiring problem on the right half may create the episodes of depression.

Dr. Mary Phillips
Position: Professor of psychiatry, University of Pittsburgh; co-director, Brain Imaging Research Center at Pitt and Carnegie Mellon University; professor of clinical affective neuroscience, University of Cardiff
Age: 44
Residence: Shadyside
Education: Bachelor's in medical sciences, Cambridge University, 1986; master's in neuroscience, Keele University, 1987; M.D. equivalent, Cambridge University, 1989; Ph.D. equivalent, Cambridge University, 2000.
Previous positions: Professor of neuroscience and head of the Neuroscience and Emotion Section, Institute of Psychiatry, London, 1997-2005.
Professional awards: Senior scientist award, Eleventh Winter Workshop on Schizophrenia Research; National Alliance for Research on Schizophrenia and Depression, Nellie Blumenthal Investigator, 2007.
Publications: More than 100 articles in refereed scientific journals.

Her study focused on a bundle of fibers known as the uncinate fasciculus, which connects an emotion-processing area known as the amygdala, at the bottom of the brain, with a regulatory area known as the orbital prefrontal cortex, at the front of the brain.

Simply put, she said, the amygdala "allows us to perceive the emotional salience" of things we experience, while the orbital prefrontal cortex areas on either side of the brain "act like brakes on the amygdala."

Her study found that on the left side of the brain, which is associated with more positive feelings, the uncinate fasciculus was much thinner than normal, which could mean the front of the brain was less able to control those feelings in bipolar patients, sending them into hyperactive, sometimes grandiose episodes of mania.

On the right side, which is more linked to negative feelings, the wiring was thicker and had more cross-connections, which she said "can lead to sort of getting off the point and thinking too much, getting off into this reverberative, ruminative loop" of anxious, melancholy ideas.

In mentally healthy people, that right-side cabling is smoother and more unidirectional, she said, which may allow the front of the brain to short-circuit any excessive negative thoughts.

To measure patients' feelings while they were in the brain scanner, Dr. Phillips' team showed them images of happy and fearful faces. Previous research has shown that people with bipolar disorder react much more strongly to fearful faces than typical people do.

Finding out what is wrong in the brains of people with bipolar disorder is an important first step, Dr. Phillips said, but the more exciting potential is to use that information to improve diagnosis and treatment.

The studies hold out the potential that "we can use neuroimaging to choose the right medication and dose" for patients.

It may also help doctors differentiate those who have bipolar disease from those who just have depression, since they are separate disorders with distinct treatments.

And someday, it could help researchers predict who is likely to develop bipolar disease, which could be crucial to offering early treatment.

Dr. Barbara Sahakian, a neuropsychology professor at Cambridge University, said at an international bipolar conference held in Pittsburgh last week that "many of the neuropsychiatric disorders that exist become chronic, and the more episodes a person has, the more difficult it is to treat them effectively, so prevention or early detection is an extremely important issue."

Dr. Phillips' work could also help resolve a controversy that has sprung up over diagnosing bipolar disease in children.

While research at Pitt has shown that children can get bipolar disorder and often suffer the most severe form of the disease, there also have been reports that some psychiatrists have been diagnosing children as bipolar without strong evidence for it.

Brain imaging "biomarkers" could help resolve those questions, she said.

Dr. Phillips, who grew up near Nottingham in Great Britain and has both an M.D. and Ph.D. from Cambridge University, spends a lot of time flying over the Atlantic.

While she lives most of the year in Pittsburgh, she flies to the United Kingdom every month to six weeks to fulfill parallel duties as a neuroscience professor at Cardiff University, and she conducts her research in both places.

She entered medical school at the age of 18 and soon knew what she wanted to focus on. "I was fascinated by psychiatric illnesses because they were so un-understandable at the time."

She also knew she wanted to work with the fast-growing field of brain imaging, which uses everything from X-rays to radioactive isotopes to magnetic fields to view what parts of the brain are active.

As a psychiatrist, she has always wanted to use the results of her imaging work to find new ways to help patients, and she believes there is the real potential of doing that with bipolar disorder, which affects an estimated 1 percent of the population, or more than 3 million people in the United States.

Her discoveries also have strengthened her belief that mental illness is centered in a dysfunctional brain. People may be born with their problems, or their illnesses may alter their brains, but either way, there are concrete changes in the structure and functioning of the brain that scientists will be able to unravel.

"People suffering from these illnesses want to know what's going on in their brains. Just like with a broken leg, you want to know where the break is -- you want to know where the break is in your brain."

With the progress being made in neuroscience, "we will be able to say, 'This is where the problem is, it's not all in your mind,' and that's going to destigmatize psychiatric illnesses more than anything."

Mark Roth can be reached at or 412-263-1130. First Published June 29, 2009 4:00 AM


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