N E U R OSC I E N C E
It's all in your head
Thanks to Canadian research, patients suffering from depression may
someday get brain scans to determine whether they should undergo talk
therapy or be prescribed a bottle of pills
B Y B R A D E V E N S O N
Andrew Solomon did not get depressed until all his problems had
disappeared. With a psychologist's help, the Manhattan writer was coping
well after his mother's death. He had written a good novel. His new
house was beautiful. He was writing for The New Yorker magazine.
And yet a day before his 32nd birthday, he lay in bed hugging his
pillow, crying in mute, tearless agony.
"Becoming depressed is like going blind," he later wrote. "The darkness
at first [is] gradual, then encompassing; it is like going deaf, hearing
less and less until a terrible silence is all around you ." Like nearly
20 million North Americans stricken with depression in any given year,
Solomon faced a bewildering choice: should he have more psychotherapy or
take anti-depressant pills? Either treatment only works for about 60% of
patients. As a gamble, that's about the same as betting on tomorrow's
weather. "In no other aspect of medicine is it hit or miss like this,"
says Helen Mayberg, a senior neuroscientist at the Rotman Research
Institute in Toronto.
Now, two surprising new studies have cast light on how to match
treatments to patients.
The research shows that talk therapy works to heal depression, but it
works on a different area of the brain than drugs. If the findings are
confirmed, patients with mental illness will someday get MRI brain scans
to determine whether they should get talk therapy or a bottle of pills.
"If you knew you could prevent the six to eight weeks of suffering that
go along with taking the wrong treatment, you could justify the expense
of an MRI," says Charles Nemeroff, chairman of the department of
psychiatry at Emory University School of Medicine in Atlanta, Ga.
Currently, from a doctor's point of view, depression is like a dark pool
of quicksand. How you sank to your chin does not matter. The symptoms
are the same for everyone.
And yet people do sink into the quicksand of depression for different
reasons. Understanding the reasons could guide doctors to choose the
In 1917, Sigmund Freud wrote that people were more vulnerable to
"melancholia" if they had suffered an early trauma, such as the
childhood loss of a parent or physical abuse. But not everyone who
suffers a breakdown has had such a life trauma; some depression patients
had happy childhoods and loving parents. Look at Andrew Solomon.
"Most people would have been pretty happy with my cards at the start,"
says the U.S. writer, who chronicled his illness in The Noonday Demon,
An Atlas of Depression (Scribner, 2001).
"I have had a good life so far and I'm grateful for it."
Unlike the blues, which most people suffer from time to time, clinical
depression involves debilitating and potentially dangerous biochemical
changes in the brain. The overwhelming sadness can lead to loss of clear
thinking, remembering or pleasure in anything. Anxiety, physical pain
and loss of energy are common. There is a greater risk of suicide.
"It is like feeling your clothing slowly turning into wood on your body,
a stiffness in the elbows and the knees progressing to a terrible weight
and an isolating immobility that will atrophy you and in time destroy
you," Solomon writes.
Between 5% and 12% of men and 10% to 20% of women in Canada will suffer
a major depression in their lifetimes. As many as 15% of people who
suffer depression or bipolar disorder - a form of depression - commit
suicide each year. The World Health Organization predicts depression
will be the highest-ranking cause of disability in developed countries
by 2020 and second only to heart disease worldwide.
Yet deciding how to treat a particular case of depression is a guessing
"What we really need is a throat culture for psychiatry," Nemeroff says.
"If you have a sore throat and you get a culture, your family doc knows
what anti-biotic to prescribe. But right now, it's really trial and
The two main treatment forms are drugs and therapy. Some patients
combine them, but many do not.
Over the past decade, drug companies have made huge strides in selling
antidepressants, partly by removing the stigma from mental illness. In a
recent Canadian TV ad campaign funded by drug companies, "depression"
stalks an executive in a washroom, warning "I can strike anyone at any
Between 1998 and September, 2003, prescriptions for anti-depressants of
all classes rose to 32.8 million from 22.6 million, an increase of 45%,
the research firm IMS Health Canada reports.
Roughly three-quarters of depression patients are now treated with
Many patients find comfort in research that casts depression as a
chemical imbalance that can be adjusted by a drug cocktail.
Anti-depressants are easy to take, relatively safe and less addictive
than many medications.
About two-thirds of those taking such drugs as SSRIs, tricyclics and MOA
inhibitors and other mood-altering pills respond. However, about 80% of
patients suffer remission within a year of quitting their medications.
By contrast, while similar numbers of patients benefit from
psychotherapy, the benefits last long after the treatment ends - only
about 25% relapse.
Patients also tend to stick with therapy longer. Yet psychotherapy has
declined in popularity because it is viewed as oldfashioned, subjective
and not as "scientific" as drugs.
In particular, those who champion drug treatment point to new research
that suggests anti-depressants may help regenerate a part of the brain's
limbic system, the hippocampus, which shrinks when a patient is
However, in a study published last week in Archives of General
Psychiatry, Dr. Mayberg shows psychotherapy can also change the brain's
In the study, 14 patients were treated with cognitive behavioural
therapy (CBT). Developed by Aaron Beck of the University of
Pennsylvania, CBT treats depression as a consequence of false logic. Dr.
Beck noticed depressed people tend to take a negative view of everything
that happens to them, magnifying disappointments into tragedies.
Patients in CBT are taught how to recognize this disparity between their
feelings and reality. As part of the treatment, they fill out worksheets
that compare their impressions of events with the facts.
The treatment is "about teaching people how to develop a more balanced
view of their thinking, especially recognizing a lot of what we call
depressive propaganda," says Zinder Segal, professor of psychiatry at
the University of Toronto, who collaborated on the study.
In the comparison arm of the study, 13 depressed patients took Paxil,
the most widely prescribed anti-depressant in Canada.
Both patient groups had depression of equal severity.
Before and during the treatments, the researchers tested the patients
with a PET scanner, which shows where the maximum activity is occurring
in the brain.
"Our expectation going into this was the brain would change in very
similar ways, regardless of which treatment you tried," Dr. Segal says.
Since anti-depressants and CBT work for roughly the same percentage of
patients, the researchers had assumed they did roughly the same job in
To their surprise, they found the treatments operated in separate
While the Paxil worked in the limbic area of the brain, CBT led to
greater activity in the frontal cortex, the so-called "mind" centre.
At first, the researchers thought they had mixed up the data. But the
findings, they realize, made sense; therapy works from the top down,
teaching patients not to ruminate forever over tiny setbacks, while
drugs work from the bottom up.
"It was a powerful demonstration that psychotherapy is a biological
treatment," Nemeroff says.
Not only do brains respond to treatment differently, Mayberg suspects
brains may respond to illness differently, too. She has found some
telltale markers of brain activity in patients that may predict how to
treat the disease.
"Doctors often ask why the patient came in on the first day," says
Mayberg, who recently left Toronto to conduct research at Emory
"It's usually because they could no longer concentrate at work or cope
at home. Their compensatory strategies just ran their course and the
illness is winning. What this picture is telling us is that . the
brain's attempts to heal itself are important.
She adds: "You want to enhance what the brain is doing to help itself."
Mayberg believes the brain's activity patterns during a depression,
combined with a patient's history, may be a guide map to the best course
There are strong clues she is on the right track. In November, U.S.
researchers published one of the largest studies ever undertaken on
depression in Proceedings of the National Academy of Sciences
(PNAS). Researchers treated 681 patients with either the anti-depressant
Serzone or psychotherapy or both. As expected, patients fared about the
same on either treatment alone and did better when the treatments were
The exception was patients who had suffered early childhood trauma. For
them, psychotherapy helped, but adding drugs to psychotherapy added
little or no benefit.
"Our results suggest that psychotherapy may be an essential element in
the treatment of patients with chronic forms of major depression and a
history of childhood trauma," the study concluded. Nemeroff, one of the
principal researchers in the PNAS study, says early life trauma lowers a
person's threshold for depression.
"If you're at genetic risk and you have a perfect life, you may not
become depressed, but if you have early life trauma, you may instantly
become depressed," he explains.
Mayberg and Nemeroff think the day is not far off when depression
patients will be scanned before treatment is prescribed, much the way
cardiac patients are now treated.
"Almost every community hospital has an MRI machine right now and these
could be made to take moving pictures of the brain," Nemeroff says.
With billions of dollars in antidepressant sales at stake, it is easy to
foresee opposition from the pharmaceutical industry.
Still, Nemeroff sees this shift as inevitable, noting all areas of drug
treatment are evolving away from one-sizefits-all drugs toward products
that are matched to a patient's genome.
"I suspect they would rather market to a patient population that is
going to do well with the drug and stay on it for a long time, than 10
times that number who are going to take it for a week and then stop
because of side effects," he says. The good news is depression is
treatable, if not curable, and the stable of therapies and drugs now at
hand can help. After many months of illness, Solomon was back on his
feet with a combination of the treatments, not cured, but better.
"Almost every day I feel momentary flashes of hopelessness and wonder
every time whether I am slipping," he writes.
"Every day I choose, sometimes gamely and sometimes against the moment's
reason, to be alive. Is that not a rare joy?"
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FRED R. CONRAD / THE NEW YORK TIMES New York writer Andrew Solomon,
photographed in the library of his home in Greenwich Village, faced a
bewildering choice of treatments when he was stricken with depression. A
combination of drugs and therapy finally worked for him.