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Apropos of our recent discussion on the survival value of PTSD, here is
an interesting expert interview from medscape psychiatry on depression.
FYI, the 1925 birth cohort had a lifetime prevalance of 4% for
depression; today it appears to be 17%; these guys say 25% but I think
that is high. In any case, it is an epidemic. <br>
LJ<br>
<br>
<a class="moz-txt-link-freetext" href="http://www.medscape.com/viewarticle/503013_print">http://www.medscape.com/viewarticle/503013_print</a> <br>
(registration required)<br>
<br>
<div class="subtitle"><a
href="http://www.medscape.com/px/viewindex/more?Bucket=columns&SectionId=2036">Expert
Interview</a></div>
<div class="title">Mood Disorders at the Turn of the Century: An Expert
Interview With Peter C. Whybrow, MD</div>
<br>
<div class="text12">Medscape Psychiatry & Mental Health. 2005; 10
(1): ©2005 Medscape</div>
<div xmlns:str="http://exslt.org/strings"
xmlns:func="http://exslt.org/functions" class="text12">
<p><i><b>Editor's Note:</b> <br>
On
behalf of Medscape, Randall F. White, MD, interviewed Peter C. Whybrow,
MD, Director of the Semel Institute for Neuroscience & Human
Behavior and Judson Braun Distinguished Professor and Executive Chair,
Department of Psychiatry and Biobehavioral Sciences, David Geffen
School of Medicine, University of California, Los Angeles. </i></p>
<p><b>Medscape:
The prevalence of mood disorders has risen in every generation since
the early 20th century. In your opinion, what is behind this?</b></p>
<p><b>Peter C. Whybrow, MD:</b>
I think that's a very interesting statistic. My own sense is that,
especially in recent years, it can be explained by changes in the
environment. The demand-driven way in which we live these days is tied
to the increasing levels of anxiety and depression. You see that in the
latest cohort, the one that was studied with the birth date of 1966,
depression has grown quite dramatically compared with those who were
born in cohorts before then. So anxiety now starts somewhere in the 20s
or 30s, and depression is also rising, so the prevalence now for most
people in America is somewhere around 25%. </p>
<p><b>Medscape: Lifetime prevalence?</b></p>
<p><b>Dr. Whybrow:</b> Yes, lifetime prevalence. </p>
<p>I
think it's a socially driven phenomenon; obviously there's not a change
in the genome. I think we've been diagnosing depression fairly
accurately for a fair length of time now, since the 1960s, and the
people who were born in the 1960s are now being diagnosed with
depression at a higher rate than those who were born earlier and who
were diagnosed in the 1960s, 1970s, and 1980s.</p>
<p><b>Medscape: And is this true of both unipolar and bipolar mood
disorders?</b></p>
<p><b>Dr. Whybrow:</b>
It's particularly true of unipolar disorder. There has been a growth in
interest in bipolar disorder, partly I think because of the zeal of
certain authors who have seen cyclothymia and other oscillating mood
states as part of a larger spectrum of manic-depressive illness, much
as Kraepelin did. And I think that has expanded the prevalence of the
bipolar spectrum to probably 5% or 6%, but the major increase in
prevalence, I think, would be diagnosed as unipolar depression. </p>
<p><b>Medscape:
Do you think that unipolar and bipolar mood disorders are distinct, or
do they lie on a continuum that includes all the mood disorders in our
nosology?</b></p>
<p><b>Dr. Whybrow:</b> The way I see it is they are
both phenotypes, but they have considerable overlap. If you think about
them from the standpoint of the psychobiology of the illnesses, I think
they are distinct. </p>
<p><b>Medscape: Why are women more vulnerable than men to depression?</b></p>
<p><b>Dr. Whybrow:</b>
My own take on that is that it is driven by the change in hormones that
you see in women. Estrogen and progesterone, plus thyroid and steroids,
are the most potent modulators of central nervous system activity. If
you tie the onset of symptoms to menarche or the sexual differentiation
in boys and girls, you find that prior to that age, which is now around
11 to 13, boys and girls have essentially the same depressive symptoms.
As adolescence appears, you find this extraordinary increase in young
women who complain of depressive symptoms of one sort or another. Boys
tend to have other things, of course, particularly what some consider
socially deviant behavior. </p>
<p>The other interesting thing one sees
quite starkly in bipolar illness is that, after the age of 50 or so,
when menopause occurs, severe bipolar illness can actually improve.
I've seen that on many occasions.</p>
<p>Also interesting and relevant
to the hormonal thesis is the way in which thyroid hormone and estrogen
compete for each other at some of the promoter regions of various
genes. In the young woman who has bipolar disease -- this is pertinent
to the work I have done over the years with thyroid hormone -- and who
becomes hypothyroid, estrogen becomes much more available in the
central nervous system, and you then see the malignant forms of bipolar
illness. Almost all the individuals who have severe rapid cycling
between the ages of about 20 and 40 are women -- high proportions,
something like 85% to 90%. So this all suggests that there is an
interesting modulation of whatever it is that permits severe affective
illnesses in women by the fluxes of estrogen and progesterone.</p>
<p>There
is, of course, a whole other component of this, which is a social
concern in regard to the way in which women are treated in our society
compared with men. It's far different from when I was first a
psychiatrist back in the 1960s and 1970s; women are much more
independent now, but there is still some element of depression being
driven in part by the social context of their lives, both in family and
in the workplace, where they still do not enjoy absolute equality.</p>
<p><b>Medscape: Why would the genotype for mood disorders persist in
the human genome? What aspect of the phenotype is adaptive?</b></p>
<p><b>Dr. Whybrow:</b>
I think you have to divide that question into 2. If we talk about
bipolar disease and unipolar disease separately, it makes more sense. </p>
<p>If
we take bipolar disease first, I think there is much in the energy and
excitement of what one considers hypomania that codes for excellence,
or at least engagement, in day-to-day activities. One of the things
that I've learned over the years is that if you find an individual who
has severe manic depressive disease, and you look at the family, the
family is very often of a higher socioeconomic level than one might
anticipate. And again, if you look at a family that is socially
successful, you very often find within it persons who have bipolar
disease.</p>
<p> So I think that there is a group of genes that codes
for the way in which we are able to engage emotionally in life. I talk
about this in one of my books called <i>A Mood Apart</i> <sup>[1]</sup>
-- how emotion as the vehicle of expression and understanding of other
people's expression is what goes wrong in depression and in mania. I
think that those particular aspects of our expression are rooted in the
same set of genes that codes for what we consider to be pathology in
manic-depressive disease. But the interesting part is that if you have,
let's say for sake of easy discussion, 5 or 6 genes that code for extra
energy (in the dopamine pathway and receptors, and maybe in fundamental
cellular activity), you turn out to be a person who sleeps rather
little, who has a positive temperament, and so on. If you get another 1
or 2 of them, you end up in the insane asylum. </p>
<p>So I think there
is an extraordinary value to those particular genetic pools. So you
might say that if you took the bipolar genes out of the human
behavioral spectrum, then you would find that probably we would still
be -- this is somewhat hyperbolic -- wandering around munching roots
and so on.</p>
<p><b>Medscape: What about unipolar disorder?</b></p>
<p><b>Dr. Whybrow:</b> Unipolar is different, I think. This was
described in some detail in <i>A Mood Apart</i> .<sup>[1]</sup>
I think that the way in which depression comes about is very much like
the way in which vision fails, as an analogy. We can lose vision in all
sorts of ways. We can lose it because of distortions of the cornea or
the lens; the retina can be damaged; we can have a stroke in the back
of our heads; or there can be a pituitary tumor. </p>
<p>I think it's
analogous in the way depression strikes: from white tract disease in
old age to the difficulties you might have following a bout of
influenza, plus the sensitivity we have to social rank and all other
social interactions. Those things can precipitate a dysregulation of
the emotional apparatus, much as you disturb the visual apparatus, and
you end up with a person who has this depressive phenomenon. In some
individuals, it repeats itself because of a particular biological
predisposition. In 30% or 40% of individuals, it's a one-time event,
which is tied to the circumstances under which they find themselves. So
I think that's a very distinct phenomenon compared with bipolar illness.</p>
<p>In
its early forms, depression is a valuable adaptive mechanism because it
does accurately focus on the fact that the world is not progressing
positively, so the person is driven to do something about it. Sometimes
the person is incapable of doing something about it, or the adaptive
mechanisms are not sufficient, and then you get this phenomenon of
depression. I know that there have been speculations about the fact
that this then leads to the person going to the edge of the herd and
dying because he or she doesn't eat, et cetera, and it relieves the
others of the burden of caring for him or her. And that might have been
true years ago, when we lived in small hunter-gatherer groups. But of
course today we profess, not always with much success, to have a
humanitarian slant, and we take care of people who have these
phenomena, bringing them back into the herd as they get better.</p>
<p>So
I think that it's a bit of a stretch to say that this has evolutionary
advantage because it allows people to go off and die, but I think that
in the bipolar spectrum there are probably genes that code for extra
activity, which we consider to have social value.</p>
<p><b>Medscape:
Let's go back to bipolar disorder. The current approach to finding new
treatments for bipolar disorder is to try medications that were
developed for other conditions, especially epilepsy. Do we know enough
yet about this disease to attempt to develop specific treatments de
novo?</b></p>
<p><b>Dr. Whybrow:</b> Well, we're getting there, but
we're not really yet in that position. You're quite right, most of the
treatments have come from either empirical observations, such a
lithium, or because there is this peculiar association between
especially temporal lobe epilepsy and bipolar disease, both in terms of
phenomena and also conceptually. But we do know more and more about the
inositol cycle, we do know something about some of the genes that code
for bipolar illness, so I think we will eventually be able to untangle
the pathophysiology of some of the common forms. </p>
<p>I think the
problem is that there are multiple genes that contribute to the way in
which the cells dysregulate, so it's probably not that we'll find one
cause of bipolar illness and therefore be able to find one medication
as we've found for diabetes, for example.</p>
<p><b> Medscape: Let's talk about your new book <i>American Mania:
When More Is Not Enough</i> , in which you use mania as a metaphor to
describe aspects of American culture.<sup>[2]</sup> </b></p>
<p><b>Dr. Whybrow:</b>
The metaphor came because of the work I've done over the years with
bipolar illness. In the late 1990s, when I first moved to California, I
was struck by the extraordinary stock-market bubble and the excitement
that went on. You may remember those days: people were convinced that
this would go on forever, that we'd continue to wake up to the sweet
smell of money and happiness for the rest of our days. This seemed to
me to have much in common with the delusional systems one sees in
mania. </p>
<p>So the whole thing in my mind began to be an interesting
metaphor for what was happening in the country, as one might see it
through the eyes of a psychiatrist watching an individual patient. I
began to investigate this, and what particularly appealed to me was
that the activity that you see in mania eventually breaks, and of
course this is exactly what happened with the bubble. Then all sorts of
recriminations begin, and you enter into a whole new phase.</p>
<p>The
book takes off from there, but it has also within it a series of
discussions about the way in which the economic model that we have
adopted, which is, of course, Adam Smith's economic model, is based
upon essentially a psychological theory. If you know anything about
Adam Smith, you'll know that he was a professor of moral philosophy,
which you can now translate into being a psychologist. And his theory
was really quite simple. On one hand, he saw self-interest, which these
days we might call survival, curiosity, and social ambition as the 3
engines of wealth creation. But at the same time, he recognized that
without social constraints, without the wish we have, all of us, to be
loved by other people (therefore we're mindful of not doing anything
too outrageous), the self-interest would run away to greed. But he
convinced himself and a lot of other people that if individuals were
free to do what they wished and do it best, then the social context in
which they lived would keep them from running away to greed.</p>
<p> If you look at that model, which is what the book <i>American
Mania: When More Is Not Enough</i>
does, you can see that we now live in a much different environment from
Smith's, and the natural forces to which he gave the interesting name
"the invisible hand," and which made all this come out for the benefit
of society as a whole, have changed dramatically. It's losing its grip,
in fact, because we now live in a society that is extremely
demand-driven, and we are constantly rewarded for individual endeavor
or self-interest through our commercial success, but very little for
the social investment that enables us to have strong unions with other
people. This is particularly so in the United States. </p>
<p>So you
can see that things have shifted dramatically and have gone into, if
you go back to the metaphor, what I believe is sort of a chronic
frenzy, a manic-like state, in which most people are now working
extremely hard. Many of them are driven by debt; other people are
driven by social ambition, but to the destruction very often of their
own personal lives and certainly to the fabric of the community in
which they live.</p>
</div>
<h3>References</h3>
<ol>
<li> Whybrow PC. <i>A Mood Apart: The Thinker's Guide to Emotions
and Its Disorders</i> . New York, NY: HarperCollins; 1997. </li>
<li> Whybrow PC. <i>American Mania: When More Is Not Enough</i> .
New York, NY: WW Norton; 2005. </li>
</ol>
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