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Saturday, May 1, 1999

Depression therapy's bright future
Neurologists have found an obscure and primitive part of the brain associated with survival instincts is linked to depression, and that Sigmund Freud's talking cure is just as effective a treatment as drugs

Brad Evenson
National Post


SAD BRAIN: These images produced using positron emission tomography (PET) scanning chart the flow of blood between the two areas of the brain associated with depression and thinking.

HAPPY BRAIN: These images produced using positron emission tomography (PET) scanning chart the flow of blood between the two areas of the brain associated with depression and thinking.

John Lehmann, National Post / Helen Mayberg, now head of neuropsychiatry at Toronto's Baycrest Centre for Geriatric Care, was part of a three-member team at the University of Texas that has discovered the brain becomes less smart when it is in a sad or depressed state.

In the summer of 1985, American author William Styron descended into a horrible depression. The renowned author of Sophie's Choice found himself awake at 3 or 4 a.m., staring into yawning darkness. Joy disappeared from his life, along with his sex drive. Even his voice seemed to shrivel. Perhaps most importantly, he lost his ability to concentrate. "My brain, in thrall to its outlaw hormones, had become less an organ of thought than an instrument registering, minute by minute, varying degrees of its own suffering," he later wrote.

Observers of human behaviour, from Plato to Freud, have noted that people consumed by sadness lose their ability to think straight. But until now scientists have not been able to show why this happens.

For the last 50 years, scientists have theorized that the tug-of-war between emotion and reason is actually a struggle between the evolutionarily "old" part of the brain, responsible for survival instincts, and the "new" areas of the brain where human cognition and reasoning reside.

Now, for the first time, scientists have "photographed" this relationship.

Using positron emission tomography (PET) scanning, a team from the University of Texas showed that with sadness, blood flows away from the "smart" part of the brain into an area of the primitive, limbic brain. The study is featured on the cover of today's American Journal of Psychiatry.

Among other things, the study proves disorders such as depression are not simply independent chemical blobs in the brain. The study shows that depression in the part of the brain dealing with emotion affects areas of the brain responsible for thinking and movement. It also illustrates -- in high-resolution colour images --why the psychiatrist's couch is often as effective as Prozac in treating the disease.

It could even explain why sexual attraction clouds our better judgment.

"Emotion affects reason; it's an axiom in neuroscience," says neurologist Helen Mayberg, lead author of the paper. "Everybody knows it. But until now, nobody's shown it."

Like many bright moments in science, this one was unexpected.

As the technology of imaging has improved during the early 1990s, scientists have been able to take pictures of the brain, usually by injecting radioactive dye that binds to blood or sugar, and then monitoring where it goes. As a young scientist, Mayberg was interested in taking images of sadness.

She began by examining post-stroke depression, trying, like many other scientists at the time, to discover how lesions in a specific part of the brain could cause a mood disorder. In neurology circles, this is known as "break a spot, something goes wrong, explain the universe."

But Mayberg suspected that depression was not an isolated blob in the brain; it had to affect other parts of the anatomy.

So she and two other University of Texas scientists began to look at patterns of change. "We wanted to cross-compare which brain areas go with which clinical symptoms," she says.

By word of mouth and by placing advertisements in Texas newspapers, they recruited eight healthy test subjects willing to feel terribly sad.

This is harder than it sounds.

If the recruits merely entertained sad thoughts, that would be thinking, not feeling, and these two processes are rooted in far different areas of the brain.

"We used an autobiographical or episodic memory, well-rehearsed, and made them sad," says Mayberg. "So we would be looking at the state of feeling bad."

The test subjects wrote their memories down in a script. One woman wrote of caring for a close friend dying of AIDS. Another described the death of a dog. On paper, the memories didn't seem so terrible. But the scientists were devastated by the live performances as they watched the test subjects sink into misery. "To be able to share with a stranger a very, very personal memory, and to actually allow yourself to emote in front of someone you don't know, it's amazing," says Mayberg.

(Actually, stage actors do it all the time. Members of the so-called "method" school of acting use personal memories to evoke emotion onstage. "Feel, don't think" is a method actor's credo, and what gave Marlon Brando's Stanley Kowalski such wrenching despair as he cried "Stellaaaa!" in the movie A Streetcar Named Desire.)

As the test subjects grew sadder, Mayberg and her colleagues took images of the activity in their brains.

As expected, blood flowed to the limbic region of the brain, which is linked to depression.

But something unexpected happened, too. Portions of the brain's right hemisphere, linked to thought and attention, were turned off during the sadness.

"When we stopped to think about it, we said, 'We're idiots'," says Mayberg.

"Because in fact, what would make you think that in a normal person you could separate mood from attention?"

For example, when people watch TV news images of death and destruction, they are consumed by their sadness, and unable to discuss, for example, why the kitchen is not clean. Interest in outside things is temporarily derailed.

The results fascinated Mayberg and her colleagues. Immediately, they began to wonder if the same phenomenon happened in patients with clinical depression.

"So we went back and looked at data we had from an experiment where we had people in hospital and we had treated them," she says.

"We had people who got better on [Prozac], and got better without drugs."

This time, the PET images showed the polar opposite effect.

After six weeks of treatment -- half with anti-depressants, half with psychotherapy -- blood flowed away from the limbic area toward the cortex, restoring them to normal.

In other words, exactly the same relationship existed between the old and new areas of the brain in sick and healthy patients.

Mayberg's results are intriguing for several reasons.

First, they shine a spotlight on an obscure area of the limbic brain known as Area 25. If the brain is shaped roughly like a clenched fist, Area 25 is one of the knuckles near the fingernails; the frontal cortex is the "punching" knuckles.

Until now, Area 25 was not considered to be "overactive" in depression; on its own, it does not appear to do much. But it's now clear Area 25 is part of a "circuit" or "loop" that must be changed if mood is to improve -- a physiological straw that breaks the camel's back, or, at least, bums him out.

Second, it illustrates that Sigmund Freud may have been right.

One of Freud's basic theories holds that behaviour is affected by primitive, emotional memories in the psyche. During the early 1880s, he developed what several of his patients called the "talking cure" to deal with their problems. The talking seemed to produce a catharsis, bursting a dam of emotional blockage at the root of their pathological behaviour.

Mayberg found that patients who underwent psychotherapy had the same brain reaction as those on Prozac. Why? She has a theory. As Area 25 fills with blood and a person becomes sad, a part of the right frontal cortex called Area 9, linked with cognition, empties out.

"When you see depressed people they get stuck in this loop," she says.

While normal people rise quickly out of sadness, an ill person will be held under, like a person drowning below a transparent sheet of ice.

"It's like they're trying to get out; you can just imagine their cortex trying to dampen this bubbling up of limbic stuff," says Mayberg.

It could be that psychotherapy, which requires talking and thinking, could increase the demand for blood in Area 9, forcing a return to normality. While antidepressants such as Prozac, Zoloft, and Paxil work by changing the chemical balance in the limbic area, bottom-up, psychotherapy works from the top down. The important thing is recognizing the road map.

Mayberg, now head of neuropsychiatry at Toronto's Baycrest Centre for Geriatric Care, has long railed against the polarization between psychiatry and neurology.

She believes her PET study may serve as a bridge between the two camps because it looks at both brain chemistry and brain anatomy. Until recently, most psychiatrists looked at the brain as a bowl full of soup. It had lots of chemicals like serotonin and norepinephrine that occasionally got stirred up. The exact shape of the surrounding grey matter was not important.

"Obviously, the answer is going to be the combined look at chemical neuro-anatomy and what chemical imbalance happened in which neural systems," says Mayberg.

This is where the greatest potential for the study lies. Because it shows depression is a moving target, new therapies can focus on blocking its progress, rather than on a specific target in the brain.

If sadness is part of a loop, then, what about other primitive emotions like anger and fear? Mayberg's PET study acts as a kind of template for other scientists to begin mapping these loops.

Could it explain why lust makes us blind?

"The idea that sex makes us stupid, we don't even need an experiment," she laughs. "But as a scientist, I would feel better if I had the empiric data."

Kidding aside, it's clear emotions can push aside or bypass our ability to think, often for good reasons.

Take fear.

Too much thinking in a life-death situation will render you extinct.

"If you think too long about whether or not the train is going to hit me or not when you're standing on the tracks and it's two feet away, it's over," notes Mayberg.

But when a fearful experience becomes tied up in memory, events that are not scary at all can trigger panic attacks, or post-traumatic stress disorder, an experience common to war veterans and accident survivors.

When neurologists look at the brains of people suffering panic attacks, the PET image of the brain's activity is identical to someone being threatened with a baseball bat. "The pathology is that you can't turn it off," says Mayberg.

Just as depression does not require a sad event to trigger it, recurrent panic does not require a hazard. It just happens, and may simply be part of human evolution, a three-inch journey across the brain to a more primitive time.

This is scant consolation to a man like William Styron, who recounted his years of depression in the admirable 1990 book, Darkness Visible. "I began to see clearly how depression had clung close to the outer edges of my life for many years . . . Thus depression, when it finally came to me, was in fact no stranger, not even a visitor totally unannounced; it had been tapping at my door for decades."

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