[Paleopsych] Adaptiveness of depression
Lynn D. Johnson, Ph.D.
ljohnson at solution-consulting.com
Wed May 25 04:26:51 UTC 2005
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.
Mood Disorders at the Turn of the Century: An Expert Interview With
Peter C. Whybrow, MD
Medscape Psychiatry & Mental Health. 2005; 10 (1): ©2005 Medscape
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.
Medscape: The prevalence of mood disorders has risen in every generation
since the early 20th century. In your opinion, what is behind this?
Peter C. Whybrow, MD: 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%.
Medscape: Lifetime prevalence?
Dr. Whybrow: Yes, lifetime prevalence.
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.
Medscape: And is this true of both unipolar and bipolar mood disorders?
Dr. Whybrow: 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.
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?
Dr. Whybrow: 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.
Medscape: Why are women more vulnerable than men to depression?
Dr. Whybrow: 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.
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.
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.
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.
Medscape: Why would the genotype for mood disorders persist in the human
genome? What aspect of the phenotype is adaptive?
Dr. Whybrow: I think you have to divide that question into 2. If we talk
about bipolar disease and unipolar disease separately, it makes more sense.
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
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 A Mood Apart  -- 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.
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.
Medscape: What about unipolar disorder?
Dr. Whybrow: Unipolar is different, I think. This was described in some
detail in A Mood Apart . 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
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.
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.
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.
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
Dr. Whybrow: 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
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.
Medscape: Let's talk about your new book American Mania: When More Is
Not Enough , in which you use mania as a metaphor to describe aspects of
Dr. Whybrow: 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
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.
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.
If you look at that model, which is what the book American Mania: When
More Is Not Enough 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.
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
1. Whybrow PC. A Mood Apart: The Thinker's Guide to Emotions and Its
Disorders . New York, NY: HarperCollins; 1997.
2. Whybrow PC. American Mania: When More Is Not Enough . New York,
NY: WW Norton; 2005.
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