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I agree, Steve. Well put.<br>
Lynn Johnson<br>
ps - glad the list is running again.<br>
<br>
Steve Hovland wrote:<br>
<blockquote type="cite" cite="mid002101c45f77$8af4ea30$210110ac@hppav">
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<div><font size="2">Repression of trauma may be an old survival
response</font></div>
<div><font size="2">that preserves the body while killing the soul.</font></div>
<div> </div>
<div><font size="2">People who have suffered a serious psychic trauma</font></div>
<div><font size="2">such as crime or incest may continue to function,
but</font></div>
<div><font size="2">they are crippled by the things they don't care
to think</font></div>
<div><font size="2">about. A frozen emotional response makes it hard</font></div>
<div><font size="2">for them to make life choices that would move them</font></div>
<div><font size="2">forward. The current problems of Michael
Jackson, for</font></div>
<div><font size="2">example, </font><font size="2">undoubtedly
result from early abuse that</font></div>
<div><font size="2">went untreated.</font></div>
<div> </div>
<div><font size="2">In terms of Goleman's work on emotional
intelligence</font></div>
<div><font size="2">these people have suffered a stroke. Sometimes
the</font></div>
<div><font size="2">repression is so complete that people can't
remember</font></div>
<div><font size="2">the cause even though they exhibit all of the
symptoms.</font></div>
<div> </div>
<div><font size="2">The challenge for unsuccessful components of a
learning</font></div>
<div><font size="2">system is to figure out how to do better. While
they are</font></div>
<div><font size="2">in their impaired state they emit poisons that
hurt the</font></div>
<div><font size="2">performance of other components. It's in the
interest</font></div>
<div><font size="2">of society to figure out how to prevent and
repair this</font></div>
<div><font size="2">damage.</font></div>
<div> </div>
<blockquote
style="border-left: 2px solid rgb(0, 0, 0); padding-right: 0px; padding-left: 5px; margin-left: 5px; margin-right: 0px;">
<div
style="font-family: arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 10pt; line-height: normal; font-stretch: normal; font-size-adjust: none;">-----
Original Message ----- </div>
<div
style="background: rgb(228, 228, 228) none repeat scroll 0%; -moz-background-clip: initial; -moz-background-inline-policy: initial; -moz-background-origin: initial; font-family: arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 10pt; line-height: normal; font-stretch: normal; font-size-adjust: none;"><b>From:</b>
<a title="HowlBloom@aol.com" href="mailto:HowlBloom@aol.com">HowlBloom@aol.com</a>
</div>
<div
style="font-family: arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 10pt; line-height: normal; font-stretch: normal; font-size-adjust: none;"><b>To:</b>
<a title="paleopsych@paleopsych.org"
href="mailto:paleopsych@paleopsych.org">paleopsych@paleopsych.org</a> </div>
<div
style="font-family: arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 10pt; line-height: normal; font-stretch: normal; font-size-adjust: none;"><b>Sent:</b>
Wednesday, June 30, 2004 8:30 PM</div>
<div
style="font-family: arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 10pt; line-height: normal; font-stretch: normal; font-size-adjust: none;"><b>Subject:</b>
[Paleopsych] why is the amygdala so sneaky?</div>
<div><br>
</div>
<div>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman">The following tidbit from an article in The
Scientific American on stress and memory gives a<span style=""> </span>neurobiological
explanation for something<span style=""> </span>Sigmund Freud
described way back in the early days of psycho-speculation…repression
and suppression.<span style=""> </span></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"> </p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman">When something ghastly happens to us, says this
piece, which derives its wisdom from Joseph LeDoux, a strange thing
happens in our brain.<span style=""> </span>The hippocampus, the
traffic center that sends material to the conscious mind, goes through
shut down.<span style=""> </span>It’s paralyzed by glucocorticooids,
stress hormones.<span style=""> </span>But something very different
happens to our fear and body-knowledge traffic center, the amygdala.<span
style=""> </span>The amygedala thrives, grows new threads of
connection to the sympathetic nervous system, and implants memories of
the frightful experience in us.<span style=""> </span>Not only ss
that memory of a nightmare event woven into our permanent store of
lessons about life, it gets woven way down at a level that can kick our
heart into a high-speed trot, get our sweat glands oozing, and tie
knots in our stomach. <span style=""> </span>But it also gets woven in
at a level that’s impossible for us to “see” and think out.</font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Here’s the question.<span style=""> </span>What
could the evolutionary value be of keeping key experiences locked in a
vault that the conscious mind can’t crack into?<span style=""> </span>Is
this one of the shortcuts the mind uses to speed up our reactions by
cutting the dither of thinking out of the process?<span style=""> </span>Is
it one of those things that helps Val Geist sprint away from a
murderous grizly bear before he has a chance to think out a response,
thus letting Val win the race with the grizzly and live another 30
years or so?</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Many of<span style=""> </span>the
responses encoded into us by this trauma-reaction process are nowhere
near as helpful as Val’s instant dash to the nearest sturdy tree, his
climb up its trunk, and his victory swing<span style=""> </span>high
in the branches above the grizzly’s head.<span style=""> </span>Many,
in fact, are paralyzing.<span style=""> </span>They’re the
high-anxiety mind-and-body freezes of extreme anxiety.<span style=""> </span>They’re
the torture-terrors of post-traumatic stress disorders.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">The Bloom Grand Unified Theory of
Everything In the Universe Including the Human Soul says that when
they’re failing, individual components of a learning system, components
like cells in the body or like bacteria in a colony, disable themselves
or worse, kill themselves off.<span style=""> </span>Why? So their
influence will be minimized.<span style=""> </span>Sp their mistaken
strategies won’t sway the decisions of the group. And so their mistakes
will stand as a warning to the others in the consultative assemblies of
collective intelligence.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Are humans disabled by their traumas
and slowed to a painful crawl by the mark of experiences they can’t
remember as a lesson to the rest of us?<span style=""> </span>If
those who suffer this sort of amygdalic sabotage can’t remember why
they are breaking out in a cold sweat and hiding in a corner, how in
the world can their agonies add to our understanding?</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Or is the bypass of consciousness an
accidental result of a system that was wired long before there was a
thinking center in the brain, long before there was a theater of
awareness beneath the dome of the skull? <span style=""> </span>Has
that old system been retained so it can take care of things too
difficult for the conscious mind to handle—tasks like digestion and
orchestrating muscles to walk or ride a bicycle?</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">One thing this amygdala-centered
understanding hints at is this.<span style=""> </span>Freud implied
that repression was a conscious act, a mistaken act of will or
cowardice.<span style=""> </span>We were conscious of the trauma when
it happened, couldn’t face its consequences, so tucked it out of sight.<span
style=""> </span>That’s not the way the LeDoux scenario explains it.<span
style=""> </span>LeDoux’s work seems to imply that our experiences
of horror trigger a system that never bothers to show the conscious
mind its perceptions and its decisions about how to handle what it sees.<span
style=""> </span>I suspect there’s a little bit of truth to both
points of view.<span style=""> </span>What do you think?<span style="">
</span>Howard</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"> </p>
<p class="MsoNormal" style="margin: 0in 0.5in 0pt;"><font size="2"><font
face="Times New Roman"><b>glucocorticoid exposure can impair LTP in
the hippocampus and can even cause atrophy of neurons there. This
phenomenon constitutes the opposite of the stress response in the
amygdala. Severe stress can harm the hippocampus, preventing the
consolidation of a conscious, explicit memory of the event; at the same
time, new neuronal branches and enhanced LTP facilitate the amygdala's
implicit memory machinery. In subsequent situations, the amygdala might
respond to preconscious information--but conscious awareness or memory
may never follow.</b> Retrieved June 30, 2004, from the World Wide Web<span
style=""> </span>EBSCOhost</font></font></p>
<p class="MsoNormal" style="margin: 0in 0.5in 0pt;"><font
face="Times New Roman" size="2">Taming stress ,<span style=""> </span>By:
Salzano, Robert, Scientific American, 00368733, Sep2003, Vol. 289,
Issue 3</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Retrieved June 30, 2004, from the
World Wide Web </font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2"><a class="moz-txt-link-freetext" href="http://web9.epnet.com/citation.asp?tb=1&_ug=sid+BB4951D1%2DC74E%2D42C7%2DAB5A%2D27F66A8435DD%40sessionmgr6+dbs+aph+cp+1+D09B&_us=hs+True+cst+0%3B2+or+Date+ss+SO+sm+KS+sl+0+dstb+KS+ri+KAAACB4A00000109+37EF&_uso=tg%5B0+%2D+db%5B0+%2Daph+hd+False+clv%5B1+%2Dscientific++american+clv%5B0+%2D20030900%2D20030900+op%5B0+%2D+cli%5B1+%2DSO+cli%5B0+%2DDT1+st%5B0+%2Damygdala+1438&cf=1&fn=1&rn=1">http://web9.epnet.com/citation.asp?tb=1&_ug=sid+BB4951D1%2DC74E%2D42C7%2DAB5A%2D27F66A8435DD%40sessionmgr6+dbs+aph+cp+1+D09B&_us=hs+True+cst+0%3B2+or+Date+ss+SO+sm+KS+sl+0+dstb+KS+ri+KAAACB4A00000109+37EF&_uso=tg%5B0+%2D+db%5B0+%2Daph+hd+False+clv%5B1+%2Dscientific++american+clv%5B0+%2D20030900%2D20030900+op%5B0+%2D+cli%5B1+%2DSO+cli%5B0+%2DDT1+st%5B0+%2Damygdala+1438&cf=1&fn=1&rn=1</a></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">EBSCOhost</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">: Taming stress ,<span style=""> </span>By:
Salzano, Robert, Scientific American, 00368733, Sep2003, Vol. 289,
Issue 3</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">An emerging understanding of the
brain's stress pathways points toward treatments for anxiety and
depression beyond Valium and Prozac</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">OVER THE CENTURIES, SOCIETY'S
APPROACHES TO TREATING the mentally ill have shifted dramatically. At
present, drugs that manipulate neurochemistry count as cutting-edge
therapeutics. A few decades ago the heights of efficacy and compassion
were lobotomies and insulin-induced comas. Before that, restraints and
ice baths sufficed. Even earlier, and we've entered the realm of
exorcisms.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Society has also shifted its view of
the causes of mental illness. Once we got past invoking demonic
possession, we put enormous energy into the debate over whether these
diseases are more about nature or nurture. Such arguments are quite
pointless given the vast intertwining of the two in psychiatric
disease. Environment, in the form of trauma, can most certainly break
the minds of its victims. Yet there is an undeniable biology that makes
some individuals more vulnerable than others. Conversely, genes are
most certainly important factors in understanding major disorders. Yet
being the identical twin of someone who suffers one of those illnesses
means a roughly 50 percent chance of not succumbing.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Obviously, biological vulnerabilities
and environmental precipitants interact, and in this article I explore
one arena of that interaction: the relation between external factors
that cause stress and the biology of the mind's response. Scientists
have recently come to understand a great deal about the role that
stress plays in the two most common classes of psychiatric disorders:
anxiety and major depression, each Of which affects close to 20 million
Americans annually, according to the National Institute of Mental
Health. And much investigation focuses on developing the next
generation of relevant pharmaceuticals, on finding improved versions of
Prozac, Wellbutrin, Valium and Librium that would work faster, longer
or with fewer side effects.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">At the same time, insights about
stress are opening the way for novel drug development. These different
tacks are needed for the simple fact that despite laudable progress in
treating anxiety and depression, currently available medications do not
work for vast numbers of people, or they entail side effects that are
too severe.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Research in this area has applications
well beyond treating and understanding these two illnesses. The
diagnostic boundary that separates someone who is formally ill with an
anxiety disorder or major depression from everyone else is somewhat
arbitrary. Investigations into stress are also teaching us about the
everyday anxiety and depression that all of us experience at times.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Out of Balance,</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">WHEN A BODY is in homeostatic balance,
various measures--such as temperature, glucose level and so on--are as
close to "ideal" as possible. A stressor is anything in the environment
that knocks the body out of homeostasis, and the stress response is the
array of physiological adaptations that ultimately reestablishes
balance. The response principally includes the secretion of two types
of hormones from the adrenal glands: epinephrine, also known as
adrenaline, and glucocorticoids. In humans, the relevant glucocorticoid
is called cortisol, also known as hydrocortisone.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">This suite of hormonal changes is what
stress is about for the typical mammal. Iris often triggered by an
acute physical challenge, such as fleeing from a predator. Epinephrine
and glucocorticoids mobilize energy for muscles, increase
cardiovascular tone so oxygen can travel more quickly, and turn off
nonessential activities like growth. (The hormones work at different
speeds. In a fight-or-flight scenario, epinephrine is the one handing
out guns; glucocorticoids are the ones drawing up blueprints for new
aircraft carriers needed for the war effort.)</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Primates have it tough, however. More
so than in other species, the primate stress response can be set in
motion not only by a concrete event but by mere anticipation. When this
assessment is accurate ("This is a dark, abandoned street, so I should
prepare to run" ), an anticipatory stress response can be highly
adaptive. But when primates, human or otherwise, chronically and
erroneously believe that a homeostatic challenge is about to come, they
have entered the realm of neurosis, anxiety and paranoia.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">In the 1950s and 1960s pioneers such
as John Mason, Seymour Levine and Jay Weiss--then at the Walter Reed
Army Medical Center, Stanford University and the Rockefeller
University, respectively-began to identify key facets of psychological
stress. They found that such stress is exacerbated if there is no
outlet for frustration, no sense of control, no social support and no
impression that something better will follow. Thus, a rat will be less
likely to develop an ulcer in response to a series of electric shocks
if it can gnaw on a bar of wood throughout, because it has an outlet
for frustration. A baboon will secrete fewer stress hormones in
response to frequent fighting if the aggression results in a rise,
rather than a fall, in the dominance hierarchy; he has a perception
that life is improving. A person will become less hypertensive when
exposed to painfully loud noise if she believes she can press a button
at any time to lower the volume; she has a sense of control.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">But suppose such buffers are not
available and the stress is chronic. Repeated challenges may demand
repeated bursts of vigilance. At some point, this vigilance may become
overgeneralized, leading an individual to conclude that he must always
be on guard--even in the absence of the stress. And thus the realm of
anxiety is entered. Alternatively, the chronic stress may be
insurmountable, giving rise to feelings of helplessness. Again this
response may become overgeneralized: a person may begin to feel she is
always at a loss, even in circumstances that she can actually master.
Depression is upon her.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Stress and Anxiety</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">FOR ITS PART, anxiety seems to wreak
havoc in the limbic system, the brain region concerned with emotion.
One structure is primarily affected: the amygdala, whi.ch is involved
in the perception of and response to fear-evoking stimuli.
(Interestingly, the amygdala is also central to aggression, underlining
the fact that aggression can be rooted in fear--an observation that can
explain much sociopolitical behavior.)</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">To carry out its role in sensing
threat, <b><span
style="background: yellow none repeat scroll 0%; -moz-background-clip: initial; -moz-background-inline-policy: initial; -moz-background-origin: initial;">the
amygdala receives input from </span>neurons in the outermost layer of
the brain, the cortex</b>, where much high-level processing takes place.<b>
Some of this input comes from parts of the cortex that process sensory
information, including<span
style="background: yellow none repeat scroll 0%; -moz-background-clip: initial; -moz-background-inline-policy: initial; -moz-background-origin: initial;">
specialized areas that recognize individual faces</span>, as well as
from the frontal cortex, which is involved in abstract associations.</b>
In the realm of anxiety, an example of such an association might be
grouping a gun, a hijacked plane and an anthrax-tainted envelope in the
same category. The sight of a fire or a menacing face can activate the
amygdala--as can a purely abstract thought.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoBodyText" style="margin: 0in 0in 0pt;"><strong><font
face="Times New Roman" size="2">The amygdala also takes in sensory
information that bypasses the cortex. As a result, a subliminal
preconsci0us menace can activate the amygdala, even before there is
conscious awareness of the trigger.</font></strong></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Imagine a victim of a traumatic
experience who, in a crowd of happy, talking people, suddenly finds
herself anxious, her heart racing. It takes her moments to realize that
a man conversing behind her has a voice similar to that of the man who
once assaulted her.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"><b>The amygdala, in turn, contacts an array of
brain regions, making heavy use of a neurotransmitter called
corticotropin-releasing hormone (CRH).</b> One set of nerve cells
projecting from the amygdala reaches evolutionarily ancient parts of
the midbrain and brain stem. These structures control the autonomic
nervous system, the network of nerve cells projecting to parts of the
body over which you normally have no conscious control (your heart, for
example). One half of the autonomic nervous system is the symigathetic
nervous system, which mediates "fight or flight." Activate your
amygdala with a threat, and soon the sympathetic nervous system has
directed your adrenal glands to secrete epinephrine. Your heart is
racing, your breathing is shallow, your senses are sharpened.</font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"><b>The amygdala also sends information back to
the frontal cortex.</b> In addition to processing abstract
associations, as noted above, the frontal cortex helps to make
judgments about incoming information and initiating behaviors based on
those assessments. So it is no surprise that the decisions we make can
be so readily influenced by our emotions. <b>Moreover, the amygdala
sends projections to the sensory cortices as well</b>, which may
explain, in part, <b>[hb: could this explain why everything goes into
slow motion in an accident?]</b> why sensations seem so vivid when we
are in certain emotional states--or perhaps why sensory memories
(flashbacks) occur in victims of trauma.</font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman">Whether it orchestrates such powerful
reimmersions or not, the amygdala is clearly implicated in certain
kinds of memory. There are two general forms of memory. Declarative, or
explicit, memory governs the recollection of facts, events or
associations. Implicit memory has several roles as well. It includes
procedural memory: recalling how to ride a bike or play a passage on
the piano. And it is involved in fear. Remember the woman reacting to
the similarity between two voices without being aware of it. In that
case, <b>the activation of the amygdala and the sympathetic nervous
system reflects a form of implicit memory that does not require
conscious awareness.<o:p></o:p></b></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Researchers have begun to understand
how these fearful memories are formed and how they can be
overgeneralized after repeated stress. The foundation for these
insights came from work on declarative memory, which is most likely
situated in a part of the brain called the hippocampus. Memory is
established when certain sets of nerve cells communicate with one
another repeatedly. Such communication entails the release of
neurotransmitters--chemical messengers that travel across synapses, the
spaces between neurons. Repeated stimulation of sets of neurons causes
the communication across synapses to be strengthened, a condition
called long-term potentiation (LTP).</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Joseph LeDoux of New York University
has shown that repeatedly placing rats in a fear-provoking situation
can bring about LTP in the amygdala. Work by Sumantra Chattarji of the
National Center for Biological Science in Bangalore extends this
finding one remarkable step further:<b><span
style="background: yellow none repeat scroll 0%; -moz-background-clip: initial; -moz-background-inline-policy: initial; -moz-background-origin: initial;">
the amygdalic neurons of rats in stressful situations sprout new
branches, allowing them to make more connections with other neurons.</span></b>
As a result, any part of the fear-inducing situation could end up
triggering more firing between neurons in the amygdala. A victim if he
had been robbed several times at night, for instance--might experience
anxiety and phobia just by stepping outside his home, even under a
blazing sun.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">LeDoux has proposed a fascinating
model to relate these changes to a feature of some forms of anxiety. As
discussed, the hippocampus plays a key role in declarative memory. As
will become quite pertinent when we turn to depression, <b>glucocorticoid
exposure can impair LTP in the hippocampus and can even cause atrophy
of neurons there. This phenomenon constitutes the opposite of the
stress response in the amygdala. Severe stress can harm the
hippocampus, preventing the consolidation of a conscious, explicit
memory of the event; at the same time, new neuronal branches and
enhanced LTP facilitate the amygdala's implicit memory machinery. In
subsequent situations, the amygdala might respond to preconscious
information--but conscious awareness or memory may never follow.</b>
According to LeDoux, such a mechanism could underlie forms of
free-floating anxiety.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">It is interesting that these
structural changes come about, in part, because of hormones secreted by
the adrenal glands, a source well outside the brain. As mentioned, the
amygdala's perception of stress ultimately leads to the secretion of
epinephrine and glucocorticoids. The glucocorticoids then activate a
brain region called the locus coeruleus. This structure in turn, sends
a powerfully activating projection back to the amygdala, making use of
a neurotransmitter called norepinephrine (a close relative of
epinephrine). The amygdala then sends out more CRH, which leads to the
secretion of more glucocorticoids. A vicious circle of mind-body
feedback can result.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Assuaging Anxiety</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">AN UNDERSTANDING of the interactions
between stress and anxiety has opened the way for new therapies, some
of which hold great promise. These drugs are not presumed better or
safer than those available today. Rather, if successful, they will give
clinicians more to work with.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">The medicines that already exist do
target aspects of the stress system. The minor tranquilizers, such as
Valium and Librium, are in a class of compounds called<b>
benzodiazepines. They work in part by relaxing muscles; they also
inhibit the excitatory projection from the locus coeruleus into the
amygdala, thereby decreasing the likelihood that the amygdala will
mobilize the sympathetic nervous system.</b> The net result is a calm
body--and a less anxious body means a less anxious brain. While
effective, however, benzodiazepines are also sedating and addictive,
and considerable research now focuses on finding less troublesome
versions.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">In their Search for alternatives,
researchers have sought to target the stress response upstream of the
locus coeruleus and amygdala. Epinephrine activates a nerve called the
vagus, which projects into a brain region that subsequently stimulates
the amygdala. A new therapy curtails epinephrine's stimulation of the
vagus nerve.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Chemical messengers such as
epinephrine exert theft effects by interacting with specialized
receptors on the surface of target cells. A receptor is shaped in such
a way that it can receive only a certain messenger-just as a mold will
fit only the statue cast in it. But by synthesizing imposter
messengers, scientists have been able to block the activity of some of
the body's natural couriers.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Drugs called beta blockers fit into
some kinds of epinephrine receptors, preventing real epinephrine from
transmitting any information. Beta blockers have long been used to
reduce high blood pressure driven by an overactive sympathetic nervous
system, as well as to reduce stage fright. But Larry Cahill and James
McGaugh of the University of California at Irvine have shown that the
drugs also blunt the formation of memories of emotionally disturbing
events or stories. Based on their findings and others, clinicians such
as Roger Pitman of Harvard University have started studies in which
beta blockers are given to people who have experienced severe trauma in
the hope of heading off the development of post-traumatic stress
disorder.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Other therapies are being designed to
act in the amygdala itself. As described, the amygdala's shift from
merely responding to an arousing event to becoming chronically
overaroused probably involves memory formation as well as the growth of
new synapses. Work in my laboratory is exploring the molecular biology
underlying those changes. Because prolonged stress has opposite effects
on synapse formation in the hippocampus and the amygdala, we would like
to know how the profiles of genes turned on and off by stress differ in
those two structures. Our goal is to then try to block the changes by
introducing genes into the amygdala that might give rise to proteins
that could inhibit synapse formation during stress. In this work,
viruses that have been rendered safe are used to ferry genes to the
amygdala [see Gene Therapy in the Nervous System, by Dora Y. Ho and
Robert M. Sapolsky; SCIENTIFIC AMERICAN, July 1997].</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Another strategy--for both anxiety and
depression--targets CRH, the neurotransmitter used by the amygdala when
it sends information elsewhere. Based on insights into the structure of
CRH and its receptors, scientists have developed chemical imposters to
bind with the receptors and block it. In research by Michael Davis of
Emory University, these compounds have proved effective in rat models
of anxiety. They have reduced the extent to which a rat anxiously
freezes when placed in a cage where it was previously shocked.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Stress and Depression</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">IN CONTRAST TO ANXIETY, which can feel
like desperate hyperactivity, major depression is characterized by
helplessness, despair,, an exhausted sense of being too overwhelmed to
do anything (psychomotor retardation) and a loss of feelings of
pleasure. Accordingly, depression has a different biology and requires
some different strategies for treatment. But it, too, can be related to
stress, and there is ample evidence of this association. First of all,
psychological stress entails feeling a loss of control and
predictability--an accurate description of depression. Second, major
stressful events seem to precede depressive episodes early in the
course of the disease. Finally, treating people with glucocorticoid
hormones to control conditions such as rheumatoid arthritis can lead to
depression.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman">One way in which stress brings about depression
is by acting on the brain's mood and pleasure pathways. To begin, <b>prolonged
exposure to glucocorticoid hormones depletes norepinephrine levels in
the locus coeruleus neurons. Most plausibly, this means that the
animal--or person--becomes less attentive, less vigilant, less active:
psychomotor retardation sets in.</b></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"><b>Continued stress also decreases levels of
serotonin</b>--which may be important in the regulation of mood and
sleep cycles, among other things--as well as the number of serotonin
receptors in the frontal cortex. Serotonin normally arrives in the
frontal cortex by way of the raphe nucleus, a structure that also
communicates with the locus coeruleus. You can probably see where this
is going. Normally, serotonin stimulates the release of norepinephrine
from the locus coeruleus. When serotonin becomes scarce, less
norepinephrine is released--exacerbating the shortage caused by earlier
unremitting glucocorticoid bombardment.</font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Stress affects dopamine, the main
currency of the pleasure pathway, in a way that seems counterintuitive
at first. Moderate and transient amounts of stress--and the ensuing
presence of glucocorticoids--increase dopamine release in the pleasure
pathway, which runs between a region called the ventral
tegmentum/nucleus accumbens and the frontal cortex. More dopamine can
lead to a feeling of well-being in situations of moderate or transient
stress during which a subject is challenged briefly and not too
severely. For a human, or a rat, this situation would entail a task
that is not trivial, but one in which there is, nonetheless, a
reasonably high likelihood of success--in other words, what we
generally call "stimulation." But with chronic glucocorticoid exposure,
dopamine production is curbed and the feelings of pleasure fade.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Not surprisingly, the amygdala also
appears relevant to depression. Wayne Drevets of the National Institute
of Mental Health reports that the images of the amygdala of a depressed
person light up more in response to sad faces than angry ones.
Moreover, the enhanced autonomic arousal seen in anxiety-- thought to
be driven by the amygdala--is often observed in depression as well.
This fact might seem puzzling at first: anxiety is characterized by a
skittish: torrent of fight-or-flight signals, whereas depression seems
to be about torpor. Yet the helplessness of depression is not a quiet,
passive state. The dread is active, twitching, energy-consuming,
distracting, exhausting--but internalized. A classic conceptualization
of depression is that it represents aggression turned inward--an
enormous emotional battle fought entirely internally--and the disease's
physiology supports this analysis.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Memory and New Cells</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">STRESS ALSO ACTS ON the hippocampus,
and this activity may bring about some of the hallmarks of depression:
difficulty learning and remembering. As I explained before, stress and
glucocorticoids can disrupt memory formation in the hippocampus and can
cause hippocampal neurons to atrophy and lose some of their many
branches. In the 1980s several laboratories, including my own, showed
that glucocorticoids can kill hippocampal neurons or impair their
ability to survive neurological insults such as a seizure or cardiac
arrest.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Stress can even prevent the growth of
new nerve cells. Contrary to long-held belief, adult brains do make
some new nerve cells. This revolution in our understanding has come in
the past decade. And although some findings remain controversial, it is
clear that new neurons form in the olfactory bulb and the hippocampus
of many adult animals, including humans [see "Brain, Repair Yourself,"
by Fred H. Gage]. Many things, including learning, exercise and
environmental enrichment, stimulate neurogenesis in the hippocampus.
But stress and glucocorticoids inhibit it.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">As would be expected, depression is
associated with impaired declarative memory. This impairment extends
beyond remembering the details of an acute trauma. Instead depression
can interfere with declarative memory formation in general--in people
going about their everyday routine or working or learning. Recent and
startling medical literature shows that in those who have been
seriously depressed for years, the volume of the hippocampus is 10 to
20 percent smaller than in well-matched control subjects. There is
little evidence that a small hippocampus predisposes someone toward
depression; rather the decreased volume appears to be a loss in
response to depression.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">At present, it is not clear whether
this shrinkage is caused by the atrophy or death of neurons or by the
failure of neurogenesis. Disturbingly, both the volume loss and at
least some features of the cognitive impairments persist even when the
depression resolves. (It is highly controversial whether new neurons
are required for learning and memory; thus, it is not clear whether an
inhibition of neurogenesis would give rise to cognitive deficits.)</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Glucocorticoids may act on the
hippocampus by inhibiting levels of a compound called brain-derived
neurotrophic factor (BDNF)--which may aid neurogenesis. Several known
antidepressants increase amounts of BDNF and stimulate hippocampal
neurogenesis in laboratory animals. These findings have led some
scientists to speculate that the stress-induced inhibition of
neurogenesis and of BDNF are central to the emotional symptoms of
depression. I find it to be somewhat of a stretch to connect altered
hippocampal function with the many facets of this disease.
Nevertheless, these hippocampal changes may play a large part in the
substantial memory dysfunction typical of major depression.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">New Drugs for Depression</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">THE CURRENT GENERATION of
antidepressants boost levels of serotonin, dopamine and norepinephrine,
and there is tremendous ongoing research to develop more effective
versions of these drugs. But some novel therapies target steps more
intimately related to the interactions between stress and depression.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Not surprisingly, some of that work
focuses on the effects of glucocorticoids. For example, a number of
pharmaceuticals that are safe and clinically approved for other reasons
can transiently block the synthesis of glucocorticoids in the adrenal
glands or block access of glucocorticoids to one of their important
receptors in the brain. Fascinatingly, the key compound that blocks
glucocorticoid receptors is RU486, famous and controversial for its
capacity to also block progesterone receptors in the uterus and for its
use as the "abortion drug." Beverly Murphy of McGill University, Owen
Wolkowitz of the University of California at San Francisco and Alan
Schatzberg of Stanford have shown that such antiglucocorticoids can act
as antidepressants for a subset of severely depressed people with
highly elevated glucocorticoid levels. These findings are made even
more promising by the fact that this group of depressed individuals
tend to be most resistant to the effects of more traditional
antidepressants.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Another strategy targets CRH. Because
depression, like anxiety, often involves an overly responsive amygdala
and sympathetic nervous system, CRH is a key neurotransmitter in the
communication from the former to the latter. Moreover, infusion of CRH
into the brain of a monkey can cause some depressionlike symptoms.
These findings have prompted studies as to whether CRH-receptor
blockers can have an antidepressant action. It appears they can, and
such drugs are probably not far off.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Using the same receptor-blocking
strategy, researchers have curbed the action of a neurotransmitter
called Substance P, which binds to the neurokinin-1 (NK-1) receptor. In
the early 1990s workers discovered that drugs binding with NK-1 prevent
some aspects of the stress response. In one trial and several animal
studies, Substance P has worked as an antidepressant.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Other approaches center on the
hippocampus. Investigators are injecting BDNF into the brains of rats
to counteract the inhibitory effects of glucocorticoids on
neurogenesis. My own laboratory is using gene therapy to protect the
hippocampus of rats from the effects of stress--much as we are doing in
the amygdala to prevent anxiety. These genes are triggered by
glucocorticoids; once activated, they express an enzyme that degrades
glucocorticoids. The net result blocks the deleterious effects of these
hormones. We are now exploring whether this treatment can work in
animals.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">As is now clear, I hope, anxiety and
depression are connected. Yet a state of constant vigilance and one of
constant helplessness seem quite different. When does stress give rise
to one as opposed to the other? The answer seems to lie in how chronic
the stress is.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">The Stress Continuum</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">IMAGINE A RAT trained to press a lever
to avoid a mild, occasional shock--a task readily mastered. Thai rat is
placed into a cage with the lever, and the anticipatory sense of
mastery might well activate the pleasurable dopaminergic projections to
the frontal cortex. When the increase in glucocorticoid secretion is
moderate and transient--as would likely be the case here--the hormone
enhances dopamine release.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Suppose that in this circumstance,
however, the lever has been disconnected; pressing it no longer
prevents shocks. Initially this alteration produces a wildly
hypervigilant state in the rat as it seeks a new coping response to
stop the shocks. The animal presses the lever repeatedly, frantically
trying to regain control. This is the essence of anxiety and of the
multiple, disorganized attempts at coping. Physiologically, this state
is characterized by massive activation of the sympathetic nervous
system by epinephrine and of the norepinephrine projection from the
locus coeruleus, as well as moderately increased glucocorticoid
secretion.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">And as the shocks continue and the rat
finds each attempt at coping useless, a transition occurs. The stress
response becomes more dominated by high glucocorticoid levels than by
epinephrine and the sympathetic nervous system--which are largely in
control of the immediate fight-or-flight reaction. The brain chemistry
begins to resemble that of depression as key neurotransmitters become
depleted and the animal ceases trying to cope. It has learned to be
helpless, passive and involuted. If anxiety is a crackling, menacing
brushfire, depression is a suffocating heavy blanket thrown on top of
it.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Stress and Genes</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">I DO NOT WANT to conclude this article
having given the impression that anxiety and depression are "all" or
"only" about stress. Obviously, they are not:. Both illnesses have
substantial genetic components as well. Genes code for the receptors
for dopamine, serotonin and glucocorticoids. They also code for the
enzymes that synthesize and degrade those chemical messengers, for the
pumps that remove them from the synapses, for growth factors like BDNF,
and so on.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">But those genetic influences are not
inevitable. Remember, if an individual has one of the major psychiatric
disorders, her identical twin has only about a 50 percent chance of
having it. Instead the genetic influences seem to be most about
vulnerability: how the brain and body react to certain environments,
including how readily the brain and body reequilibrate after stress.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Experience, beginning remarkably early
in life, also influences how one responds to stressful environments.
The amount of stress a female rat is exposed to during pregnancy
influences the amount of glucocorticoids that cross the placenta and
reach the fetus; that exposure can then alter the structure and
function of that fetus's hippocampus in adulthood. Separate a newborn
rat from its mother for a sustained period and it will have increased
levels of CRH as an adult. Seymour Levine, One of the giants of
psychobiology, illustrates this point with a quotation from William
Faulkner: "The past is not dead. It's not even the past."</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">An understanding of the role of stress
in psychiatric disorders offers much. It teaches us that a genetic
legacy of anxiety or depression does not confer a life sentence on
sufferers of these tragic diseases. It is paving the way for some new
therapies that may help millions. Given that there is a continuum
between the biology of these disorders and that of the "normal" aspects
of emotion, these findings are not only pertinent to "them and their
diseases" but to all of us in our everyday lives. Perhaps most
important, such insight carries with it a social imperative: namely,
that we must find ways to heal a world in which so many people learn
that they must always feel watchful and on guard or that they must
always feel helpless.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">SOME NOVEL THERAPEUTIC STRATEGIES</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Substance P. This compound is released
during painful sensations and stress and are found throughout the
central nervous system but in greater amounts in the amygdala and locus
coeruleus, among other stress related areas. Current work-including one
clinical trial--suggests that blocking the action of Substance P may
blunt anxiety and depression. But another clinical trial did not
support this finding.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Corticotropin-Releasing Hormone. This
hormone is released by the amygdala and initiates the stress cascade.
Research efforts now include trying to block receptors for CRH in the
brain stem. Without information from CRH, the brain stem will not set
the sympathetic nervous system in motion,, thus preventing the release
of epinephrine by the adrenal glands. This blockade could block anxiety
and depression.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Brain-Derived Neurotrophic Factor.
This substance is important to the creation of new nerve cells. By
injecting BDNF into brains, researchers hope to counteract the
deleterious effects of glucocorticoids on neurogenesis in the
hippocampus, thereby maintaining healthy memory function and preventing
the hippocampal atrophy often seen in depressed people.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Gene Therapy. This treatment can
introduce novel genes to specific regions of the brain; these genes can
then produce proteins that can undo or prevent the effects of stress.
Current studies aim to figure out which genes are active in the
amygdala during stress. Introducing genes that inhibit unwanted neural
branching in the amygdala might then thwart the anxiety-inducing
effects of stress. For depression, the goal is different: genes placed
in the hippocampus could produce proteins that would break down
glucocorticoids, preventing damage to nerve cells-and, accordingly, the
memory impairment-that can accompany depression.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Anxiety becomes depression if stress
is chronic and levels of dopamine [D}, glucocorticoids [ G} and
epinephrine [E} change accordingly. If a rat knows how to press a lever
to avoid a shock, it can feel pleasure in that mastery. If the lever no
longer works, however, anxiety sets in and the animal desperately tries
different strategies to avoid the shock (2}. As coping proves elusive,
hypervigilance is replaced by passivity and depression (3).</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">MORE TO EXPLORE</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Why Zebras Don't Get Ulcers. Robert M.
Sapolski. W. H. Freeman and Company, 1998.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">The End of Stress as We Know It. Bruce
McEwen, with Elizabeth Norton Lasley. Joseph Henry Press, Washington
D.C., 2002.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Better Than Prozac. Samuel H.
Barondes. Oxford University Press, 2003.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">OVERVIEW / Battling Stress</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">• Scientists understand a lot about
the role stress plays in the development of anxiety disorders and major
depression, which may affect as many as 40 million people in the U.S.
And they are coming to see the ways in which unremitting stress can
transform anxiety into depression.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">• Insights into the neurochemistry of
stress are allowing researchers to develop new ways of thinking about
drug development. In addition to refining drugs that are already on the
market, these findings are leading to entirely novel strategies for
treatments.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">• Finding these alternatives is
crucially important because many people are not helped by currently
available medications.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">VICIOUS CYCLE OF STRESS</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">STRESS PATHWAYS are diverse and
involve many regions of the brain in feedback loops that sometimes
greatly amplify a response. The process-simplified somewhat in this
diagram-begins when an actual or perceived threat activates the sensory
and higher reasoning centers in the cortex. The cortex then sends a
message to the amygdala, the principal mediator of the stress response.
Separately, a preconscious signal my precipitate activity in the
amygdala. The amygdala releases corticotropin-releasing hormone, which
stimulates the brain stem to activate the sympathetic nervous system
via the spinal cord. In response, the adrenal glands produce the stress
hormone epinephrine; a different pathway simultaneously triggers the
adrenals to release glucocorticoids. The two types of hormones act on
the muscle, heart and lungs to prepare the body for "fight or flight".
If the stress becomes chronic, glucocorticoids induce the locus
coeruleus to release norepinephrine that communicates with the
amygdala, leading to the production of more CRH- and to ongoing
reactivation of stress pathways.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">DEPRESSION'S EFFECTS</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">DOPAMINE DEPLETION</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Prolonged exposure to stress hormones
can increase the risk of depression by depleting levels of dopamine.
This neurotransmitter is integral to the pleasure pathway, which
involves many brain structures, including the prefrontal cortex.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">NOREPINEPHRINE DEPLETION</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Because stimulation from the raphe
nucleus falls off after chronic stress, the locus coeruleus secretes
less norepinephrine, and attentiveness is accordingly diminished.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">SEROTONIN DEPLETION</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Stress brings about reduced secretion
of the neurotransmitter serotonin from the raphe nucleus, which
communicates with the locus coerlueus and the cortex.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">HIPPOCAMPAL SHRINKAGE</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Stress brings about cell death in the
hippocampus- and studies have found that this brain region is 10 to 20
percent smaller in depressed individuals. Such impairment can lead to
memory problems.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">DIAGRAM</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">DIAGRAM</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">GRAPH</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">GRAPH</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">GRAPH</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">PHOTO (COLOR)</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">PHOTO (COLOR)</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">PHOTO (COLOR)</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">~~~~~~~~</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">By Robert Salzano</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font size="2"><font
face="Times New Roman"> <o:p></o:p></font></font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">ROBERT SAPOLSKY is professor of
biological science and neurology at Stanford University and a research
associate at the National Museums of Kenya, where he has studied a
population of wild baboons for more than two decades. He earned a Ph.D.
in neuroendocrinology from the Rockefeller University in 1984.
Sapolsky's research interests include neuronal death, gene therapy and
the physiology of primates.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Copyright of Scientific American is
the property of Scientific American Inc. and its content may not be
copied or e-mailed to multiple sites or posted to a listserv without
the copyright holder`s express written permission. However, users may
print, download, or e-mail articles for individual use.</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Source: Scientific American, Sep2003,
Vol. 289 Issue 3, p88, 10p</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"><font
face="Times New Roman" size="2">Item: 10544899</font></p>
<p class="MsoNormal" style="margin: 0in 0in 0pt;"> </p>
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</div>
<div> </div>
<div><font lang="0" face="Arial" size="2" ptsize="10"
family="SANSSERIF">----------<br>
Howard Bloom<br>
Author of The Lucifer Principle: A Scientific Expedition Into the
Forces of History and Global Brain: The Evolution of Mass Mind From The
Big Bang to the 21st Century<br>
Visiting Scholar-Graduate Psychology Department, New York University;
Faculty Member, The Graduate Institute<br>
<a class="moz-txt-link-abbreviated" href="http://www.howardbloom.net">www.howardbloom.net</a><br>
<a class="moz-txt-link-abbreviated" href="http://www.bigbangtango.net">www.bigbangtango.net</a><br>
Founder: International Paleopsychology Project; founding board member:
Epic of Evolution Society; founding board member, The Darwin Project;
founder: The Big Bang Tango Media Lab; member: New York Academy of
Sciences, American Association for the Advancement of Science, American
Psychological Society, Academy of Political Science, Human Behavior and
Evolution Society, International Society for Human Ethology; advisory
board member: Youthactivism.org; executive editor -- New Paradigm book
series.<br>
For information on The International Paleopsychology Project, see:
<a class="moz-txt-link-abbreviated" href="http://www.paleopsych.org">www.paleopsych.org</a><br>
for two chapters from <br>
The Lucifer Principle: A Scientific Expedition Into the Forces of
History, see <a class="moz-txt-link-abbreviated" href="http://www.howardbloom.net/lucifer">www.howardbloom.net/lucifer</a><br>
For information on Global Brain: The Evolution of Mass Mind from the
Big Bang to the 21st Century, see <a class="moz-txt-link-abbreviated" href="http://www.howardbloom.net">www.howardbloom.net</a><br>
</font></div>
<p> </p>
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</blockquote>
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