Train Your Mind, Change Your Brain – Sharon Begley Excerpt: Mind over Matter – pages 141-150
Just as the UCLA scientists were discovering that a mind-based, cognitive therapy
can change the brain—that thinking about your thoughts in a certain way can alter
the electrical and chemical activity of a brain circuit—science was embroiled in a
bitter debate over whether psychotherapy has any effect whatsoever, let alone on
the physical structure and activity of the brain. The controversy centered on
depression. On December 29, 1987, the U.S. Food and Drug Administration had
given the pharmaceutical giant Eli Lilly and Company approval to sell fluoxetine
hydrochloride as a treatment for depression. Marketed as Prozac, the drug was
featured on the covers of magazines, starred in newspaper stories, inspired
bestselling books, and was soon racking up $2 billion in annual sales. Prozac was
not just another drug for depression. It was hailed as a compound that specifically
targeted the disease's underlying neurochemical cause, supposedly a paucity of the
neurotransmitter serotonin in the brain's synapses. The rise of Prozac coincided
with the continuing fall from grace of psychotherapy. Expensive, time-consuming,
and the subject of more jokes than rigorous scientific studies, psychotherapy was
starting to have the whiff of something as antediluvian as Freud's couch.
Which is not to say that psychotherapists were throwing in the towel. To the
contrary. In 1989, scientists reported the results of the most ambitious study ever
undertaken to examine the effectiveness of psychotherapy compared to medication
in treating depression. Called the Treatment of Depression Collaborative Research
Project, this two-year study was funded and organized by the National Institute of
Mental Health. Two hundred and fifty outpatients with major depression were
randomly assigned to receive one of four treatments: interpersonal psychotherapy,
cognitive-behavior therapy, imipramine (a common antidepressant), or an inert
pill. In the last two cases, patients also received what is called clinical
management, which essentially means they saw a psychiatrist to receive their
Train Your Mind, Change Your Brain – Sharon Begley Excerpt: Mind over Matter – pages 141-150
Cognitive-behavior therapy, which was developed in the 1960s, does not dwell
on causes of depression. It focuses instead on teaching patients how to handle their
emotions, thoughts, and behaviors. The idea is to reappraise dysfunctional
thinking, to see the fallacy of thoughts such as "The fact that I was not offered that
job means I am doomed to be unemployed and homeless." Patients learn to think
about their thoughts differently and not to ruminate endlessly about minor
setbacks. Instead of seeing a failed date as evidence that "I am a total loser, and no
one will ever love me," patients learn to view it as just one of those things that
didn't work out. Instead of seeing a leaky roof as a sign that "nothing will ever go
right for me," they think of it as "Stuff happens." They learn to recognize their
tendency to magnify disappointments into calamities and mishaps into tragedy, and
to test the accuracy of their extreme beliefs. If they are convinced that no one will
ever like them, the therapist encourages them to join a social group and strike up a
conversation and possibly a friendship. Such reality testing will show patients that
they are unrealistically pessimistic. With their newfound cognitive skills, patients
can experience sadness and setbacks without being sucked into the black hole of
Interpersonal therapy, on the other hand, recognizes that although depression
may not be caused by interpersonal relations or experiences, it affects them. It
therefore targets interpersonal disputes and conflicts, role transitions such as
becoming an empty nester, and complicated and persistent grief.
In all four groups, patients suffered fewer symptoms of depression over the
sixteen weeks of the study. Imipramine produced the greatest improvement in the
most severely depressed patients, placebo the least, with the two psychotherapies
in between. For patients whose depression was mild to moderate, however, the two
psychotherapies produced results on a par with those of the medication. "The
power of the cognitive behaviour therapies in [depression] is considerable,
certainly equal to the power of the standard drug treatments for depression," Gavin
Andrews, professor of psychiatry at the University of New South Wales in
Train Your Mind, Change Your Brain – Sharon Begley Excerpt: Mind over Matter – pages 141-150
Australia wrote in the British Medical Journal in late 1996. "If these psychological
treatments had been drug treatments they would have been certified as effective
and safe remedies and be an essential part of the pharmacopoeia of every doctor.
As they were not developed by profit making companies, and thus are not
marketed or promoted, their use often languishes." Despite this and subsequent
studies validating the efficacy of psychotherapy for depression, it has been tough to
shake the perception that psychotherapy is ineffective and inferior to medication.
While the NIMH study was under way, a young psychologist named Zindel Segal
was studying depression. He recalls of the drugs-versus-psychotherapy debate that
"the sides were drawn very sharply. There was a productive fractiousness, with
psychologists saying there was good evidence for the efficacy of therapy" but
many scientists convinced that psychotherapy has no place in a Prozac world.
Rather than attacking the efficacy question straight on, Segal decided to study
whether psychotherapy has an effect on a different, but arguably even more
important, aspect of depression: the rate of relapse.
Depression is notorious for its frequent and cruel relapses. A patient may finally
feel she has broken the chains of her illness, only to plunge back into the abyss of
despair, as 50 percent do. Because of the high relapse rate, patients suffer an
average of four major episodes of depression lasting about five months each over
the course of their lives. "Many people continue to become ill," says Segal. "The
typical progression, unfortunately, is that treatment brings relief, but the risk of
relapse or recurrence remains high. Sustained recovery from depression is not the
rule." Indeed, doctors and patients had begun noticing that antidepressants come
with a dark side: unless patients continue taking the medication, they are very
likely to suffer a relapse within two years of the initial treatment. Most patients,
says Segal, "require treatment beyond the point when their symptoms disappear."
Train Your Mind, Change Your Brain – Sharon Begley Excerpt: Mind over Matter – pages 141-150
That was disappointing, of course. But it was also interesting for the
possibilities it suggested about the relative benefits of psychotherapy and
antidepressants. "The thinking at the time was that psychotherapy, especially
cognitive therapy, might produce lasting changes in people's attitudes and beliefs
about themselves, which would protect them well after the end of the therapy,"
says Segal. "Some beliefs make people vulnerable to relapse, like the idea that
asking for help is a sign of weakness or that always being right is the way to get
others to respect you. If a person with these attitudes suffers a minor setback, even
after successful treatment for depression, their explanations for what this means
about them—they are weak, they will never be respected—make them more likely
to spiral down into depression. What we proposed was that if cognitive therapy
could modify these attitudes, then the risk of relapse would be reduced."
That hunch was based on the fact that cognitive therapy is, in essence, a form of
mental training. It teaches patients a different way of approaching their thoughts.
In the case of depression, those thoughts are, all too often, sad, glum, bleak, or
otherwise "dysphoric." Everyone gets those thoughts now and then, of course.
What's different in patients with depression is that the thought tips them over the
emotional edge into an abyss of negative, hopeless thinking powerful and sustained
enough to trigger a full-blown episode of (typically) months-long depression. A
setback at work or a romantic rejection escalates to "Nothing will ever go right for
me; life is hopeless, and I will always be a complete loser." As described above,
cognitive therapy teaches patients to think about these triggering thoughts and
feelings so they do not bring on a cascade of depression-triggering thoughts and
major depression itself but instead become "short-lived and self-limiting," as John
Teasdale of the University of Cambridge, England, suggested.
Here's why cognitive therapy looked as if it might be more efficacious than
antidepressants in preventing relapse: the ease with which this type of
dysfunctional thinking is triggered by dysphoria reliably predicts the likelihood
that a patient will suffer a relapse of depression. If cognitive therapy can break the
Train Your Mind, Change Your Brain – Sharon Begley Excerpt: Mind over Matter – pages 141-150
connection between sadness and aberrant, wildly exaggerated extrapolations,
maybe it can vanquish the very mechanism that leads to relapse. It was analogous
to how Schwartz taught his OCD patients to think about their obsessions as a
fleeting misfire of their brain, one they had the power to keep from exploding into
pointless and disruptive compulsions. But first, Segal had to see whether the basic
hypothesis was right: that sad thoughts unleash beliefs that make people vulnerable
So he made people sad. By then head of the Cognitive Behaviour Therapy
Clinic at the Center for Addiction and Mental Health in Toronto, he recruited
thirty-four people who had been successfully treated for depression within the
previous twenty-four months. To induce sadness, he had two surefire methods:
asking the volunteers to think about a time when they felt sad and having them
listen to Prokofiev's Russia under the Mongolian Yoke. Played at half-speed, Segal
says, it induces five to ten minutes of deep sadness as reliably as Beth's death scene
Once the volunteers were feeling blue, Segal asked them to indicate how much
they agreed or disagreed with statements such as "If I fail at my work, then I am a
failure as a person," "If someone disagrees with me, it probably indicates he does
not like me," "If I don't set the highest standards for myself, I am likely to end up
as a second-rate persons"—all known to reveal whether someone holds attitudes
that make him vulnerable to depressive relapse.
Segal found that when people had been made melancholic by remembering a
sad episode in their lives or listening to the brooding Slavic melody, they were
much more likely to hold these attitudes. "The experience of depression can
establish strong links in the mind between sad moods and ideas of hopelessness
and inadequacy," he says. "Through repeated use, this becomes the default option
for the mind: it's like mental kindling. Even among recovered depressed patients,
the degree to which sad moods 'switch on' these attitudes is a significant predictor
Train Your Mind, Change Your Brain – Sharon Begley Excerpt: Mind over Matter – pages 141-150
of whether the patient will relapse eighteen months later." In some people, sad
thoughts unleash beliefs that put them at risk for depression.
For these unfortunate souls, successful treatment for depression helps with
sleeplessness and other symptoms but leaves their gnawing personal doubt intact.
As long as things go well, they can sidestep the doubt. But if they suffer a setback
or reversal and become sad, this way of thinking creeps back in: "Yeah, things
really are hopeless; I was stupid to believe otherwise," or "I really can't hold on to
a relationship; I should just accept that." The acute setback makes them feel
hopeless, worthless, unloved—exactly the state of mind that characterizes the deep
despair and even paralysis of depression. Their memory works in such a way as to
activate these concepts more strongly, and with greater probability, once the
emotion of sadness arises. This makes it more likely that the brain's whole
depression network will switch on. "The experience of depression imprints a
tendency to fall back on certain patterns of thinking and to activate certain
networks in working memory," Segal says.
What these patients needed, he realized, was a different way to relate to the
inevitable sadness everyone experiences at one time or another, a way that would
not let a passing sense of unhappiness (from schmaltzy music, no less) send them
tumbling down the rabbit hole of depression. And for that, they needed to forge
In 1992, Segal met with Cambridge's John Teasdale and Mark Williams to turn his
theory of depressive relapse—that people who hold despairing attitudes are more
vulnerable to falling back into depression as a result of minor setbacks—into a
treatment. Teasdale, who had been practicing mindfulness meditation for a number
of years, had been learning about a mindfulness program developed by Jon
Train Your Mind, Change Your Brain – Sharon Begley Excerpt: Mind over Matter – pages 141-150
Kabat-Zinn of the University of Massachusetts, a longtime participant in the Mind
and Life Institute's meetings with the Dalai Lama. Although Kabat-Zinn used it
mostly for stress reduction, Teasdale saw other possibilities: to harness the power
of the mind to treat depression. He suspected that patients might escape repeated
descents into clinical depression if they learned to regard depressive thoughts
"simply as events in the mind," as he put it. The key would be to help patients
become aware of their thoughts and relate to them as merely brain events rather
than as absolute truths. Instead of letting a bleak experience or thought kindle
another episode of depression as predictably as a spark ignites a fire in bone-dry
kindling, instead of allowing their feeling to drag them down into the pit of
depression, patients would learn to respond with "Thoughts are not facts" or "I can
watch this thought come and go without having to respond to it." That, Teasdale
suspected, might break the connection the brain made between momentary
unhappy thoughts and the memories, associations, and patterns of thinking that
inflate sadness into depression. It would be like putting a wall of asbestos between
the spark and the kindling. It would be, literally, rewiring the brain.
The program the scientists developed, called mindfulness-based cognitive
therapy, consisted of eight weekly individual sessions, each lasting two hours.
Using the mindfulness training pioneered by Kabat-Zinn, the patients steered their
attention to one region of the body after another, trying to focus intently on the
sensations their hand, knee, foot was feeling at that moment. They then learned to
focus on their breathing. If their mind wandered, they were to acknowledge it with
"friendly awareness"—not frustration or anger—and focus once again on the
breath, which served as a magnet pulling them back to mindful awareness of the
moment. The patients also practiced at home, trying to notice their thoughts
impartially rather than reacting to them, and regarding their feelings and thoughts
(especially the bleak, despairing ones) as merely transient mental events that
happen to "come and go through the mind" and that are no more significant than a
Train Your Mind, Change Your Brain – Sharon Begley Excerpt: Mind over Matter – pages 141-150
butterfly floating into your field of vision. Most crucially, they kept telling
themselves that the thoughts did not reflect reality.
To assess the power of mindfulness to prevent the relapse of depression,
Teasdale, Segal, and Williams randomly assigned half of their 145 patients (all of
whom had suffered at least one past episode of major depression in the previous
five years) to receive mindfulness-based cognitive therapy and half to receive their
usual care. After eight weeks of mindfulness-based treatment, the scientists
followed the patients for an additional year.
Treatment as usual left 34 percent of the patients free of relapse. With
mindfulness-based cognitive therapy, 66 percent remained relapse-free, Teasdale
and his colleagues reported in 2000. That translates to a 44 percent reduction in the
risk of relapse among those who received mindfulness-based cognitive therapy
compared to those receiving usual care. Interestingly, the preventive effect of
mindfulness was found only in patients who had suffered three or more past
episodes of depression, who made up three-fourths of the sample. These were not
easy patients. They had what is called a recurrent form of depression and suffered
many, many depressive episodes. Yet mindfulness-based cognitive therapy nearly
halved the rate of relapse. This was the first evidence that mental training can
reduce the rate of relapse in depression.
In 2004, Teasdale and his colleague Helen Ma replicated the findings, showing
again that mindfulness-based cognitive therapy reduced relapse. This time, in a
study of fifty-five patients, they found that for patients with three or more episodes
of major depression, the rate of relapse fell from 78 percent in the
treatment-as-usual group to 36 percent in the mindfulness-based cognitive therapy
group. "Mindfulness-based cognitive therapy," they concluded, "is an effective and
efficient way to prevent relapse/recurrence in recovered depressed patients with
three or more previous episodes." Or as Segal put it, "There are modes of thinking
which are more easily triggered the more they're accessed. Mindfulness works to
keep you from triggering the depression network." By monitoring their own
Train Your Mind, Change Your Brain – Sharon Begley Excerpt: Mind over Matter – pages 141-150
thoughts, patients who practice mindfulness are able to keep the dysfunctional
products of their mind from cascading into full-blown depression.
You don't have to believe in any spooky power of mind over brain to guess
what might be happening in these patients. Somehow, mental training was altering
brain circuits, in what we might call top-down plasticity, since it originates in the
brain's cognitive processes. ("Bottom-up" plasticity is the kind that arises when
plain old sensory inputs resculpt the brain, as they do when dyslexic children hear
specially crafted sounds or lab monkeys carry out a repetitive finger motion.)
Brain-imaging technology would show precisely how mindfulness meditation was
training the mind to alter brain circuitry.
Neuroscientist Helen Mayberg had not endeared herself to the pharmaceutical
industry by discovering, in 2002, that antidepressants and inert pills—placebos—
have identical effects on the brains of depressed people. In patients who recover,
whether their treatment consisted of one of the widely prescribed selective
serotonin reuptake inhibitors (SSRIs) such as Paxil or a placebo that they thought
was an antidepressant, brain activity changed in the same way, she and colleagues
at the University of Texas Health Science Center, San Antonio, found: according
to fMRI scans, activity in the cortex increased and activity in limbic regions fell.
Based on that finding, she figured that cognitive-behavior therapy would act via
the same mechanism. Soon after the University of Toronto recruited her away from
Texas; she therefore asked Zindel Segal to collaborate on a study to see whether
there are differences between how cognitive-behavior therapy and antidepressants
"I definitely expected there must be a common pathway," Mayberg said. "I'd
thought about doing psychotherapy while I was at Texas, but there was no one
Train Your Mind, Change Your Brain – Sharon Begley Excerpt: Mind over Matter – pages 141-150
qualified to work with me on a study like that. But in Toronto, I met Zindel. It was
The Toronto scientists first used PET imaging to measure activity in the brains
of depressed patients. Then they had fourteen depressed adults undergo fifteen to
twenty sessions of cognitive-behavior therapy. Thirteen other patients received
paroxetine (the generic name of the antidepressant sold as Paxil by
GlaxoSmithKline). All twenty-seven had depression of approximately equal
severity and experienced comparable improvement after treatment. Then the
scientists scanned the patients' brains again. "Our hypothesis was, if you do well
with treatment for depression, your brain will have changed in the same way no
matter which treatment you received," says Segal.
Mayberg's study showing that the brain's response to placebo and to
antidepressant has the same pathway had made her expect that there is only one
route through brain circuitry from depression to recovery. But no. "We were totally
dead wrong," she said. Depressed brains responded differently to the two kinds of
treatment. Cognitive-behavior therapy muted over-activity in the frontal cortex, the
seat of reasoning, logic, analysis, and higher thought—as well as of endless
rumination about that disastrous date. Paroxetine, in contrast, raised activity there.
Cognitive-behavior therapy raised activity in the hippocampus of the limbic
system, the brain's emotion center. Paroxetine lowered activity there.
The differences were so dramatic that Mayberg "thought we were doing
something wrong in how we were analyzing the data," she said. "With
cognitive-behavior therapy, activity in the frontal cortex was turned down, activity
in the hippocampus was turned up—it was the opposite pattern of antidepressants.
Cognitive therapy targets the cortex, the thinking brain, reshaping how you process
information and changing your thinking pattern. We finally convinced ourselves
Putting it in terms of mind rather than brain, cognitive-behavior therapy
"decreases rumination, decreases the personal relevance of triggers that once tipped
Train Your Mind, Change Your Brain – Sharon Begley Excerpt: Mind over Matter – pages 141-150
you into depression, increases reappraisal of thoughts," Mayberg explains. "Does a
lousy date really mean that I am a failure as a human being and will never be
loved? Cognitive-behavior therapy also increases new patterns of learning, as
reflected in the increased activity in the hippocampus, the brain structure
associated with the formation of new memories. It trains the brain to adopt
different thinking circuits, to switch off ruminative modes of thinking, and to
practice relating differently to negative thoughts and feeling. Cognitive-behavior
therapy works from the top down, and drugs work from the bottom up,"
modulating different components of the depression circuit. Mindfulness-based
cognitive therapy keeps the depression circuit from being completed.
It may seem surprising that mindfulness-based cognitive therapy should work
so well in depression, targeting a system quite different from what a barrage of
commercials and friendly media coverage have insisted is the basis for
depression—namely, a shortage of the neurochemical serotonin. From the
development of the first drug, Prozac, that apparently acted by keeping serotonin
from being eliminated from the brain's synapses, it has been drummed into our
heads that depression reflects a biochemical imbalance and that Prozac or another
SSRI is the avenue to recovery. After the arrival of Prozac was greeted like the
second coming of penicillin, however, reality set in. Prozac takes several weeks to
work, when it works at all (some one-third of patients with depression do not
respond to it). It has a high relapse rate, and many patients seem to need to stay on
"Massive marketing has depicted the challenge in depression as one of
correcting a chemical imbalance in the brain," says Zindel Segal. "This may be true
at the neural level, but we now know that there are multiple pathways to recovery,
and a chemical imbalance itself can be restored in different ways."
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