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<DIV><FONT size=2>Thanks.</FONT></DIV>
<BLOCKQUOTE
style="PADDING-RIGHT: 0px; PADDING-LEFT: 5px; MARGIN-LEFT: 5px; BORDER-LEFT: #000000 2px solid; MARGIN-RIGHT: 0px">
<DIV style="FONT: 10pt arial">----- Original Message ----- </DIV>
<DIV
style="BACKGROUND: #e4e4e4; FONT: 10pt arial; font-color: black"><B>From:</B>
<A title=eshel@tamar.tau.ac.il href="mailto:eshel@tamar.tau.ac.il">Eshel
Ben-Jacob</A> </DIV>
<DIV style="FONT: 10pt arial"><B>To:</B> <A title=paleopsych@paleopsych.org
href="mailto:paleopsych@paleopsych.org">The new improved paleopsych list</A>
</DIV>
<DIV style="FONT: 10pt arial"><B>Sent:</B> Thursday, July 01, 2004 8:53
AM</DIV>
<DIV style="FONT: 10pt arial"><B>Subject:</B> Re: [Paleopsych] why is the
amygdala so sneaky?</DIV>
<DIV><BR></DIV>
<DIV><FONT face="Comic Sans MS" size=2>Dear Steve,</FONT></DIV>
<DIV><FONT face="Comic Sans MS" size=2>Liked your message.</FONT></DIV>
<DIV><FONT face="Comic Sans MS" size=2>You might be interested in the attached
papers.</FONT></DIV>
<DIV><FONT face="Comic Sans MS" size=2>All the best, Eshel</FONT></DIV>
<DIV><FONT face="Comic Sans MS" size=2></FONT> </DIV>
<DIV><FONT size=2>Eshel Ben
Jacob
E-mail: </FONT><A
href="mailto:eshel@tamar.tau.ac.il"><FONT
size=2>eshel@tamar.tau.ac.il</FONT></A><BR><FONT size=2>Professor of
Physics
Home Page: </FONT><A href="http://star.tau.ac.il/~eshel/"><FONT
size=2>http://star.tau.ac.il/~eshel/</FONT></A><BR><FONT size=2>School of
Physics and
Astronomy <BR>The
Maguy-Glass Chair in Physics of Complex Systems<BR>Tel Aviv University, 69978
Tel Aviv, Israel<BR>President of the Israel Physical
Society
Visit the IPS on-line
magazine
<BR>
</FONT><A href="http://physicaplus.org.il"><FONT
size=2>http://physicaplus.org.il</FONT></A><BR><FONT size=2>Tel #’s Country
(972) City (3) Home: (972-3) 644-8265<BR>Office: 640-7845;
Secretary: 640-7604; Fax: 642-5787; <BR>Laboratory: 640-8066;
640-8261</FONT></DIV>
<BLOCKQUOTE
style="PADDING-RIGHT: 0px; PADDING-LEFT: 5px; MARGIN-LEFT: 5px; BORDER-LEFT: #000000 2px solid; MARGIN-RIGHT: 0px">
<DIV style="FONT: 10pt arial">----- Original Message ----- </DIV>
<DIV
style="BACKGROUND: #e4e4e4; FONT: 10pt arial; font-color: black"><B>From:</B>
<A title=shovland@mindspring.com href="mailto:shovland@mindspring.com">Steve
Hovland</A> </DIV>
<DIV style="FONT: 10pt arial"><B>To:</B> <A title=paleopsych@paleopsych.org
href="mailto:paleopsych@paleopsych.org">The new improved paleopsych list</A>
</DIV>
<DIV style="FONT: 10pt arial"><B>Sent:</B> Thursday, July 01, 2004 4:27
PM</DIV>
<DIV style="FONT: 10pt arial"><B>Subject:</B> Re: [Paleopsych] why is the
amygdala so sneaky?</DIV>
<DIV><BR></DIV>
<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><FONT size=2></FONT> </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><FONT size=2></FONT> </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><FONT size=2></FONT> </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><FONT size=2></FONT> </DIV>
<BLOCKQUOTE
style="PADDING-RIGHT: 0px; PADDING-LEFT: 5px; MARGIN-LEFT: 5px; BORDER-LEFT: #000000 2px solid; MARGIN-RIGHT: 0px">
<DIV style="FONT: 10pt arial">----- Original Message ----- </DIV>
<DIV
style="BACKGROUND: #e4e4e4; FONT: 10pt arial; font-color: black"><B>From:</B>
<A title=HowlBloom@aol.com
href="mailto:HowlBloom@aol.com">HowlBloom@aol.com</A> </DIV>
<DIV style="FONT: 10pt arial"><B>To:</B> <A
title=paleopsych@paleopsych.org
href="mailto:paleopsych@paleopsych.org">paleopsych@paleopsych.org</A>
</DIV>
<DIV style="FONT: 10pt arial"><B>Sent:</B> Wednesday, June 30, 2004 8:30
PM</DIV>
<DIV style="FONT: 10pt arial"><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="mso-spacerun: yes"> </SPAN>neurobiological explanation for
something<SPAN style="mso-spacerun: yes"> </SPAN>Sigmund Freud
described way back in the early days of psycho-speculation…repression and
suppression.<SPAN style="mso-spacerun: yes">
</SPAN></FONT></FONT></P>
<P class=MsoNormal style="MARGIN: 0in 0in 0pt"><FONT size=2><FONT
face="Times New Roman"><SPAN
style="mso-spacerun: yes"></SPAN></FONT></FONT> </P>
<P class=MsoNormal style="MARGIN: 0in 0in 0pt"><FONT size=2><FONT
face="Times New Roman"><SPAN style="mso-spacerun: yes"></SPAN>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="mso-spacerun: yes"> </SPAN>The hippocampus, the traffic
center that sends material to the conscious mind, goes through shut
down.<SPAN style="mso-spacerun: yes"> </SPAN>It’s paralyzed by
glucocorticooids, stress hormones.<SPAN style="mso-spacerun: yes">
</SPAN>But something very different happens to our fear and body-knowledge
traffic center, the amygdala.<SPAN style="mso-spacerun: yes">
</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="mso-spacerun: yes"> </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="mso-spacerun: yes"> </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="mso-spacerun: yes"> </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="mso-spacerun: yes"> </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="mso-spacerun: yes"> </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="mso-spacerun: yes"> </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="mso-spacerun: yes"> </SPAN>high in the branches
above the grizzly’s head.<SPAN style="mso-spacerun: yes">
</SPAN>Many, in fact, are paralyzing.<SPAN
style="mso-spacerun: yes"> </SPAN>They’re the high-anxiety
mind-and-body freezes of extreme anxiety.<SPAN
style="mso-spacerun: yes"> </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="mso-spacerun: yes"> </SPAN>Why? So their
influence will be minimized.<SPAN style="mso-spacerun: yes">
</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="mso-spacerun: yes">
</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="mso-spacerun: yes"> </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="mso-spacerun: yes">
</SPAN>Freud implied that repression was a conscious act, a mistaken act
of will or cowardice.<SPAN style="mso-spacerun: yes"> </SPAN>We were
conscious of the trauma when it happened, couldn’t face its consequences,
so tucked it out of sight.<SPAN style="mso-spacerun: yes">
</SPAN>That’s not the way the LeDoux scenario explains it.<SPAN
style="mso-spacerun: yes"> </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="mso-spacerun: yes"> </SPAN>I suspect there’s a
little bit of truth to both points of view.<SPAN
style="mso-spacerun: yes"> </SPAN>What do you think?<SPAN
style="mso-spacerun: yes"> </SPAN>Howard</FONT></P>
<P class=MsoNormal style="MARGIN: 0in 0in 0pt"><SPAN
style="mso-spacerun: yes"><FONT face="Times New Roman"
size=2></FONT></SPAN> </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="mso-spacerun: yes"> </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="mso-spacerun: yes"> </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>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</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="mso-spacerun: yes"> </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; mso-highlight: yellow">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; mso-highlight: yellow"> 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; mso-highlight: yellow"> 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>
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<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>www.howardbloom.net<BR>www.bigbangtango.net<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:
www.paleopsych.org<BR>for two chapters from <BR>The Lucifer Principle: A
Scientific Expedition Into the Forces of History, see
www.howardbloom.net/lucifer<BR>For information on Global Brain: The
Evolution of Mass Mind from the Big Bang to the 21st Century, see
www.howardbloom.net<BR></FONT></DIV>
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