[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.

(registration required)

Expert Interview 
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

Editor's Note:
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 
bipolar disease.

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 [1] -- 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 .[1] 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 
de novo?

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 
common forms.

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 
American culture.[2]

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 
in mania.

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 
they live.


   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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