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The Anxiety Cure
An Eight-Step Program for Getting Well, Completely Revised and Updated
By Robert L. DuPont Elizabeth DuPont Spencer Caroline M. DuPont
John Wiley & Sons
Copyright © 2003
Robert L. DuPont, Elizabeth DuPont Spencer, Caroline M. DuPont
All right reserved.
The Anxious Brain
Scientists all over the world are now studying the anxious brain. Since
the first edition of this book was published in 1998,understanding of the
biology of anxiety has changed so profoundly that this chapter has been
completely rewritten. It is no accident that so much creative energy, and
so much money, is now being spent on the anxiety problem. As recently
as the 1980s,the anxiety disorders were thought to be both uncommon
and virtually untreatable. Anxiety disorders were considered by most
mental health practitioners and researchers to be trivial compared to the
"major" mental disorders-the psychotic disorders such as schizophrenia
and major depression. People suffering from anxiety were called, disparagingly,
"the worried well."
Attitudes within the mental health field toward clinically significant
anxiety have changed completely for two reasons. First, modern epidemiological
studies of mental disorders, using more scientificdiagnostic
categories, have shown that the anxiety disorders are the most
widespread or prevalent of all of the mental disorders, exceeding even
major depression and all of the other affective disorders combined. Second,
studies of the economic costs of major groups of mental disorders
have shown that the anxiety disorders are far from trivial. Anxiety disorders
produce higher costs to society than any other class of mental disorders.
Most of this high cost is the result of lost productivity at work.
As a direct result of this new knowledge, research funded by the
National Institutes of Health and by major pharmaceutical companies
has increased. Today government and private research together devote
hundreds of millions of dollars a year to the study of anxiety.
These dramatic changes offer new hope to people who suffer from anxiety
problems as better treatments are being developed and brought into
practice. An example of these promising developments is the explosive
growth of the use of new medicines to treat anxiety. Another example is
the greater appreciation for the specific and effective form of nonmedication
therapy for anxiety problems. This form of treatment is called
cognitive-behavioral treatment (CBT). The uses of better medicines
and better psychological treatments are at the heart of this book.
All three of us have been at the center of these important new developments
through our active work with the Anxiety Disorders Association
of America (ADAA). ADAA has been the biggest factor in showing
that the anxiety disorders are not only common and serious but, even
more important, that they can be treated successfully. The ADAA has
successfully linked research, practice, and consumer to the benefit of all
For more than two decades, we have worked with many pharmaceutical
companies in developing new medicines and in finding new uses for
some older medicines in the treatment of the anxiety disorders.
Together we have conducted hundreds of sophisticated double-blind
clinical trials of medicines in the treatment of the anxiety disorders. In
this work we have been joined by researchers in all parts of the country
and around the world as the anxiety disorders have become one of the
most active areas of research in contemporary medicine. In our clinical
practices we use these new pharmaceutical advances and the ever-improving
cognitive-behavioral treatment to our patients.
In this chapter we look at the explosive growth in understanding of
the biology of fear and anxiety. In Chapter 4 we look specifically at the
new medicines used in the treatment of anxiety problems.
The Brain Biology of Fear
The brain is made up of more than 100 billion nerve cells connected to
each other in a fabulously complex interactive network. Each nerve cell,
or neuron, communicates with the many other neurons across tiny
spaces, called synapses, between the connected neurons. Messages are
carried from one neuron to others by a chemical messenger called a neurotransmitter.
Brain biology can be looked at by focusing on the neuronal
circuitry used to connect the various parts of the brain with each
other and with the organs in the body that express the brain's activity,
such as the muscles and hormone systems. In addition to studying the
brain's circuitry, the biology of the brain can be understood by studying
the neurotransmitters used to send signals from one neuron to the next.
Brain mechanisms of anxiety can be studied in the laboratory by measuring
neurotransmitter levels in blood, urine, saliva, and spinal fluid; by
assessing behavior and behavioral responses to pharmacologic challenges
to specific neurochemical systems; and by measuring brain structures
using neuronal imaging. Useful studies of anxiety have been
conducted with both laboratory animals and human subjects.
The Fear Circuits
First let's look at the brain's circuitry that manages fear. From our five
senses (sight, sound, smell, taste, and touch)come sensory impulses from
all parts of our bodies into the nerve center in the midbrain called the
thalamus. This is the brain's sensory clearinghouse. In the thalamus, sensory
information of all kinds and from all sources that involve possible
danger is split into two major pathways, the high road and the low road.
The low road is the fast and automatic road for handling fear. It is
designed to respond to possible danger practically instantaneously.
Speed is important because signs of danger that can be life threatening
can occur on a split-second basis. From the thalamus the sensory inputs
travel via the low road to the amygdala and the hippocampus in the temporal
lobe of the brain. These brain structures are part of the limbic system
that manages memory and emotions. The hippocampus is especially
important because it assigns context and emotional meaning to the constant
flow of sensory inputs into the limbic system from the thalamus
night and day. When the hippocampus identifies a familiar sensory pattern
it assigns it a "safe" value if the person's past exposure to that pattern
has been benign. When the hippocampus identifies an unfamiliar
sensory pattern, or one that has been seen as dangerous in the past, it
assigns a "dangerous" value to it. Context is important to the interpretation
of sensory inputs over the low road. For example, a loud bang at
a Fourth of July fireworks show is considered to be "safe" while a similar
noise in the workplace or at home would usually be considered "dangerous."
People with a damaged hippocampus often overgeneralize
sensory inputs, treating even familiar sensory inputs as unfamiliar and
therefore assigning them the emotional meaning of being dangerous.
From the hippocampus, the brain information judged to be dangerous
travels to many centers, including the locus ceruleus (LC),the
brain's alarm or panic center. This small but very important collection
of nerve cells is located in the pons in the brainstem, right in the center
of the base of the brain. After input from the hippocampus arrives in the
LC, the danger signals in the brain are sent to sites of action to deal with
the danger. These recipients of danger messages from the LC include
the hormone center of the brain, the hypothalamus. There danger signals
trigger the pituitary hormones associated with responses to stress.
Signals go from the LC to many other parts of the brain, including the
Brain's parietal cortex, which controls the muscles needed for the fight-or-fight
responses to danger. The low road brain circuitry functions
without conscious thought. It is an emergency automatic pilot that manages
immediate responses to danger. This is the primitive, basic brain
system to manage fear and danger.
The second brain circuit that manages responses to danger-the high
Road-also starts with sensory inputs that flow from all parts of the body
into the thalamus. However, unlike the low road, this brain circuit routes
the signals from the thalamus to the cortex of the brain, the gray matter
on the brain's surface. In particular, signals involving fear are carried to
the medial prefrontal cortex of the brain. This is the gray matter on the
outside of the brain toward the front of the head. This is the part of
the brain needed for conscious thought, the formulation of ideas, and
the attribution of meaning. The cortex is needed to provide complex
analysis of a wide range of sensory inputs, including those that are sent
from the thalamus relating to possible danger. The prefrontal cortex is
where judgment is added to the mix of brain signals.
The cortex is the most highly developed and largest part of the human
brain. An extensive brain cortex is distinctive in humans and closely
related animals such as monkeys, although all mammals have some cerebral
cortex in their brains. When the cortex is removed from laboratory
animals, they lack judgment with respect to possible dangers. Strikingly,
they exhibit more fear than when they have functioning cortex material.
This experiment shows that the brain's cortex is involved in moderating
as well as managing reactions to possible danger.
Both the high road and the low road circuits have important roles in
the brain's responses to danger. Once danger is perceived by either road,
the brain mobilizes the fight-or-fight response to stress. This involves
changes in stress hormones, regulation of breathing and blood flow, and
motor responses such as those needed to run away from the danger.
These same fundamental brain mechanisms can be mobilized not only
by actual dangers but by thoughts of danger that arise from specific cues
that have been associated with past dangers. The brain learns from experiences.
Past fear reactions are particularly powerful in shaping future
behaviors. When an experience has been repeatedly associated with fear
and danger, then even the anticipation of that experience, even the
thought of it, triggers the cascade of brain changes associated with danger
When you take a child to a Fourth of July fireworks display for the
first time, the child lacks an adequate context from past experience into
which he or she can put what is about to happen. The bright lights and
the incredibly loud explosions are, in themselves, terrifying to a young
child. Before the sun sets and the fireworks display begins, loving adults
(usually that means the child's parents) explain what is to come. The
adults hold the child's hand or sit the child in their laps for reassurance.
Using the words from the adults, the child's prefrontal cortex reframes
the dramatic sensory inputs. From the words of the trusted adults the
child's brain changes the sensory signal produced by the explosions in
the sky from "dangerous" to "fun." The high road brain circuit receives
the low road signal of danger because the sensory input from the fireworks
is completely unfamiliar; therefore, it is automatically experienced
as dangerous. Thanks to the adults' reassuring words, the high road has
additional and vitally important information. The explanation from caring
adults changes the meaning of the powerful sensory input. That is
the effect of the brain's cortex, the effect of conscious thought that is provided
by the high road.
The next time the child experiences Fourth of July fireworks, not only
will the cortex offer reassurance but also, unlike the first time the child
saw the flashes and heard the booms from the fireworks, the hippocampus
will provide information about the context of these dramatic sensory
inputs. This important information from the hippocampus on the second
exposure will come from the brain's low road fear circuit. Like the
information coming from the child's prefrontal cortex, this information
will change the meaning of the sensory inputs from the thalamus, reversing
the meaning and therefore the behavioral responses. The sensory
input itself arriving into the thalamus, and sent out from there via both
the high road and the low road, is not changed. But the meaning attributed
to that sensory input is completely transformed by the information
provided within the brain from both the high road and the low road as
the experience of fireworks becomes familiar and well known to the child
to be safe and fun.
In our example, even in the first exposure to the fireworks there was
more going on in the child's brain than merely the verbal reassurance given
by the adults. The adults held the child close when the fireworks display
began. This gave context to the sensory inputs on the first exposure to the
fireworks even though those extreme sensory inputs were utterly without
precedent for the child and even though loud noises are one of the
few innate fear-generating stimuli for all mammals regardless of their
Now let's give this first exposure to fireworks another context.
Assume that the adults did not help the child but were busy with their
own interests as the time drew near for the fireworks display to begin.
Since the adults had no fear of fireworks they simply assumed that the
child would not fear them either. Or, even worse, the adults and older
children the child revered might laugh at the young child's fear over such
an innocent holiday display. Think about how the child would process
this experience under those circumstances. Not only would the fireworks
be terrifying but the child would feel alone and humiliated. Think
of how that child would react to the next exposure to fireworks. In this
version of the story, the inputs from both the high road and the low road
would not be reassuring. In this scenario we have sensitization to fear
reactions incorporated into the brain. In this scenario both the high road
and the low road are primed for heightened fear reactions on future
exposures that are judged to be similar and that may be generalized
beyond just Fourth of July fireworks to include many other potentially
Before leaving this holiday story, let us do some more changing, this
time about the child. When it comes to fears, all three-year-olds are no
more alike than are all parents. Some three-year-olds have fear mechanisms
that are set on a hair trigger. It does not take much to scare these
kids. A child like that might not be fully reassured in the dark as the fireworks
are exploding overhead, even by the most considerate and nurturing
Or the child could have been born with a fear mechanism that had a
safety lock on the fear trigger. In other words, some children are all but
impervious to fear. In these virtually fearless children the LC rarely fires
off its signal of danger. In this scenario, even with careless, preoccupied
parents this child would be untroubled by even the most dramatic fireworks
Here is yet one more observation about this common experience of
fireworks: notice how closely related fear and excitement are in the
Excerpted from The Anxiety Cure
by Robert L. DuPont Elizabeth DuPont Spencer Caroline M. DuPont
Copyright © 2003 by Robert L. DuPont, Elizabeth DuPont Spencer, Caroline M. DuPont.
Excerpted by permission.
All rights reserved. No part of this excerpt may be reproduced or reprinted without permission in writing from the publisher.
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