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May 9
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“Pain or suffering of any kind, if long continued,
causes depression and lessens the power of
action; yet it is well adapted to make a
creature guard itself against any great or
sudden evil.”
The Life and Letters of Charles Darwin,
Charles Darwin, 1887

This is a bit of a dangerous post, but so is depression.

The post is largely based on Nesse 2000, ‘Is Depression an Adaptation?’, which I heavily quote from.

Take home message if you don’t have time to read all the article:

Some negative and passive aspects of depression may be
useful because they inhibit dangerous or wasteful actions in situations
characterized by committed pursuit of an unreachable goal,
temptations to challenge authority, insufficient internal reserves to allow
action without damage, or lack of a viable life strategy.

Though, the author also points out that many depressions are disease states - so the notion that depression is an adaptive response might only be a subset of the range of potential depressions.

Continue to read to learn the more fleshed out idea:

I think most of us can agree that depression causes an immense level of suffering, for the person undergoing to depression, but also for the rest of the people close to the depressed. However, with such a large percentage of the population (see depression’s cost to the individual and society) experiencing this malady one might wonder if depression has a ‘function’. And this point Darwin was trying to convey in the opening quote of this piece.

Okay, if we are going to entertain this notion we must still wonder what could possibly( be the function of depression?

Nesse, offers a number of possibilities but emphasizes the idea that depression may play a role in drastically reducing motivation for unreachable goals.

If a commitment to pursue a goal encounters an obstacle, efforts increase and become aggressive. If the obstacle cannot be overcome, low mood helps to disengage the commitment
and end the cycle. If the individual cannot disengage, low mood escalates. Klinger concludes, “depression is ordinarily, therefore, a normal, adaptive part of disengaging oneself from an incentive.”56(p21).

If failure to reach a goal might induce depression to ‘encourage’ the organism to stop pursuing a particular goal (that is unobtainable), then one might surmise that those seeking the highest goals might suffer more depression in an attempt by the system to alter the pursuit of lofty goals.

Clinicians have long noted that depression is common in people who
are pursuing unreachable goals.47,48 “Failure to yield” may be an example,
in the status competition domain, of this more general situation.
When current life plans are not working, the distress and lack of motivation
that characterize depression may motivate planning and reassessment49
or escape, even by suicide.50

To bring in some neuroeconomic aspects to shine light on this problem one needs to think of the commitment of resources (time and energy) in pursuit of a goal with payoff X. Obviously the loftier the goal the greater potential reward, but also the probability is lower. However, if feedback with the environment is indicating that this goal is unobtainable for a particular individual there is a need for a signal to stop pursuing this ‘unprofitable’ wager.

In the article Nesse quotes Wender and Klein:

. . . biologically based self-esteem— and mood in general—seems to us to
have evolutionary utility . . . If one is subject to a series of defeats, it pays to
adopt a conservative game plan of sitting back and waiting and letting others
take the risks. Such waiting would be fostered by a pessimistic outlook.
Similarly if one is raking in the chips of life, it pays to adopt an expansive risk
taking approach, and thus maximize access to scarce resources.73(p204)

This starts becoming interesting and I would like to refer you to a couple articles I have written about optimism and hope (The neuroscience of hope, optimism is good for your health, is the glass half full or half empty: rACC brain activation, are organisms by nature optimists?).

This line of thinking suggests that depending on your probability of success one needs to appropriately adjust your ratio of optimism/pessimism. Of course this just makes common sense that we adjust our behavior based on probability of success, however the question is does depression play a role in adjusting your ‘attitude’, your goals?

Going back to Darwin, one needs to think of how something that seems so hideous like depression would actually improve ‘fitness’ (fitness defined as reproductive success - passing on the genes). If depression reduces the pursuit of an unobtainable goal, and forces a reassessment of the persons overall situation, and an eventual choosing of a goal that will result in a payoff then this could increase the person’s fitness level - then maybe depression could improve the individuals fitness.

I will give an example. Take a 21 year old person who moves to Paris (or Prague, etc) to become an artist (just to take a well know dream/pursuit) for that is their passion. They have an incredible level of drive and determination. This person does whatever is needed to pursue their goal of becoming an artist. Of course it is difficult, as is becoming an actor, athlete, etc. Despite the dogged determination this person has had very little success when nearing their 29th birthday. They might continue to pursue their goal, supplementing their income with low-income, temporary work like they have been doing for the last 8 years. But their reproductive fitness in the culture is low - they are not considered a ‘good catch’ due to the uncertainty of their future, and total lack of success (money or otherwise). Now if the person becomes depressed because of their lack of success and lose all motivation to create their art, this might induce them to give up on their dream. Having abandoned their dream they start a normal job, say based somewhat on their background, as a graphic designer for computer games. The person doesn’t consider themselves an artist for they do not get to draw what they want, but instead what they are told. But the person becomes gainfully employed and his reproductive fitness increases.

However, since depression inhibits all activity then it might just contribute the person to staying in their current situation. If you are stuck in a well and depressed then you don’t have the mental energy to attempt climbing out. This would be a bit of a paradox to the potential adaptive advantage of depression. Nesse then argues that a quick dropping of a dream and a mad rush of to a new un-thought out pursuit would also be disadvantageous.

When depression is instead seen as a state shaped to cope with unpropitious
situations, it is clear how it could be useful, both to decrease investment
in the current unsatisfying life enterprise and also to prevent
the premature pursuit of alternatives. Failure to disengage can
cause depression, and depression can make it harder to disengage. This
may explain why the low-mood system is so prone to getting stuck in
positive feedback loops.88-91 Mood dysregulation may now be so prevalent
because we are bereft of kin, beliefs, and rituals that routinely extracted
our ancestors from such cycles.92

Nesse suggests that he conundrum of depression resulting from failure in life is resolved by accepting the reality of the individual’s life situation. And then the person moves on by giving up on the unlikely probability of their former goal. How this exactly happens was less clear to me. However, what was clear is that if the person fails to disengage then ‘serious pathology‘ is likely to occur.

Earlier in Nesse article he uses the example of an animal behavioral choices while foraging a food patch.

As the food in a patch is depleted, organisms give up on that patch at close to
the optimal time, namely, when the rate of return in the current patch declines
below the average rate of return over all patches. If the overall
rate of return from all patches drops below the cost, foraging stops.

Nesse then returns to this theme when discussing the neuroeconomics of the choice of people when it is apparent they need to move on. Changing your goal engagement is considerably more difficult than simply jumping to the next food patch because of the emotional investment in these various goals.

At least as important as the risks and costs of making a
change is the threat to the person’s identity, reputation, and sense of a
secure place in a social network and the cosmos.

At the end of his paper Nesse offers a few testable hypotheses, which are interesting.

The simplest untested prediction is that depression should be
common in people who are unable to disengage from unreachable goals.
Graduate students who are failing and faculty who are unlikely to make
tenure are obvious candidates for study, but other situations are far
more common: unrequited love, inability to get work, pursuing an elusive
large life goal….

Ability to repress such wishes should prevent depression.

Finally, Nesse wonders about the possibility that foraging/feeding patterns may be linked with the behavior of depression.

If the brain mechanisms that regulate foraging are related to those that mediate depression, then antidepressants should change the duration of foraging time in a depleted patch and the willingness to exert effort even when the net rate of return is negative. They might also change preferences for working hard for a large intermittent reward vs easily getting small, frequent rewards. If low mood is an active coordinated state, then the brain mechanisms that mediate it can be blocked at different points, so antidepressants should be effective via multiple mechanisms.

I find this last point particularly intriguing as I have written previously about the relationship between antidepressants and antipsychotic use, increase levels of ghrelin, and subsequent weight gain.

Take home message:

I guess one needs to know when to hold them, and when to fold them. In specific situations depression may be a signal emanating from your system to give up. The trick is not to give up on life, but rather only give up on the specific unobtainable goal. But on the other side of the coin, ‘what if life without a dream’.

I do not know if a subset of depressions is an evolved adaptive response to stop us from chasing after fruitless endeavors (empty food patches), but it does provide food for thought.

(some of Nesse’s followup papers: Nesse 2004Keller and Nesse, 2005, Keller and Nesse 2006, Nesse and Ellsworth 2009.)

Mar 5

Sadly, there are far too many people that could describe what suicidal depression feels like. Then the question become who might best share and educate the world of what this feels like.

David Foster Wallace (DFW) is arguably the greatest writer of his generation, and sadly is intimate with this subject matter. His novel, Infinite Jest, is considered one of the greatest 100 novels of all time.

Please take the time to read what DFW has to say - if you are going to read one thing about how depression feels please read what DFW has to say.

In this short story, ‘The Planet Trillaphon‘ published in 1984 in the Amherst Review DFW describes depression (which he called the Bad Thing) as:

Imagine feeling really sick to your stomach. Almost everyone has felt really sick to his or her stomach, so everyone knows what it’s like: it’s less than fun. OK. OK. But that feeling is localized: it’s more or less just your stomach. Imagine your whole body being sick like that: your feet. the big muscles in your legs, your collar bone, your head, your hair, everything, all just as sick as a fluey stomach. Then, If you can imagine that, please imagine it even more spread out and total. Imagine that every cell in your body, every single cell in your body is as sick as that nauseated stomach. Not just your own cells, even, but the e. coli and lactobacilli in you, too, the mitochondria, basal bodies, all sick and boiling and hot like maggots in your neck, your brain, all over, everywhere, in everything. All just sick as hell. Now imagine that every single atom in every single cell in your body is sick like that, sick, intolerably sick. And every proton and neutron in every atom. . . swollen and throbbing, off·color, sick, with just no chance of throwing up to relieve the feeling. Every electron is sick, here, twirling off balance and all erratic in these funhouse orbitals that are just thick and swirling with mottled yellow and purple poison gases, everything off balance and woozy. Quarks and neutrinos out of their minds and bouncing sick all over the place bouncing like crazy. Just imagine that, a sickness spread utterly through every bit of you, even the bits of the bits. So that your very … very essence is characterized by nothing other than the feature of sickness; you and the sickness are, as they say, “one.”

From this passage you might get a sense of why depression is the 3rd leading cause of lost years, lost productivity in developed nations (Lopez et al., 2006) (see depression, lifespan and lost years).

DFW suffered from severe depression and had taken antidepressants for over twenty years. Due to complications with long term use of his particular antidepressants and a number of personal reasons stopped taking his medication. He describes what is was like after a month of no antidepressants (via The New Yorker article):

This is the harshest phase of the ‘washout process’ so far; it’s a bit like I imagine a course of chemo would be.

If I had a choice between chemotherapy or the feelings of suicidal depression I would easily choose going through chemo again and say, ‘please sir can I have some more’ when compared to the alternative.

Later in the same short story DFW writes more about the Bad Thing:

Because the Bad Thing not only attacks you and makes you feel bad and puts you out of commission, it especially attacks and makes you feel bad and puts out of commission precisely those things that are necessary In order for you to fight the Bad Thing, to maybe get better, to stay alive. This is hard to understand. but it’s really true. Imagine a really painful disease that, say, attacked your legs and your throat and resulted in a really bad pain and paralysis and all·around agony in these areas. The disease would be bad enough, obviously, but the disease would also be open·ended; you wouldn’t be able to do anything about it. Your legs would be all paralyzed and would hurt like hell … but you wouldn’t be able to run for help for those poor legs, just exactly because your legs would be too sick for you to run anywhere at all. Your throat would burn like crazy and you’d think it was just going to explode … but you wouldn’t be able to call out to any doctors or anyone for help, precisely because your throat would be too sick for you to do so. This is the way the Bad Thing works: it’s especially good at attacking your defense mechanisms. The way to fight against or get away from the Bad Thing is clearly just to think differently, to reason and argue with yourself, just to change the way you’re perceiving and sensing and processing stuff. But you need your mind to do this, your brain cells with their atoms and your mental powers and all that, your self, and that’s exactly what the Bad Thing has made too sick to work right. That’s exactly what it has made sick. It’s made you sick in just such a way that you can’t get better. And you start thinking about this pretty vicious situation, and you say to yourself, “Boy oh boy, how the heck is the Bad Thing able to do this?” You think about it really hard, since it’s in your best interests to do so - and then all of a sudden it sort of dawns on you … that the Bad Thing is able to do this to you because you’re the Bad Thing yourself! The Bad Thing is you.

DFW committed suicide September 12, 2008 by hanging himself (see death of a genius). He was loved by his wife, had a very supportive family, and admired and adored by a large group of readers - but this was not enough to save him. Think for a moment of all the depressed people out there with no one to turn to in the time of need (see the value of a human life).

However, not all people that have these feeling commit suicide - so we can’t lose hope.

As a society we must do something to try to rescue the lives of those suffering from depression. And we need to rethink our approach and catch people before they are too far along the tragic road, before they start the road as DFW describes in the same short story:

When you kill yourself. All this business about people committing suicide when they’re “severely depressed;” we say, “Holy cow, we must do something to stop them from killing themselves!” That’s wrong. Because all these people have, you see, by this time already killed themselves, where it really counts. By the time these people swallow entire medicine cabinets or take naps in the garage or whatever, they’ve already been killing themselves for ever so long. When they “commit suicide,” they’re just being orderly. They’re just giving external form to an event the substance of which already exists and has existed in them over time.

We can’t afford to wait until people get to the point where they are physically living but already dead.

All I can say is don’t give up - keep hope and seek help in whatever form that might help you. Hope, hope, hope.

Mar 4

We as a society need to find ways to protect this delicate gift we call a mind.

I don’t know if it has been formerly studied, but it seems like some of the most gifted people in the world suffer from various forms of mental diseases - with depression being very prominent. I say this without any references, and in reality I hope I am wrong. I am wishing that someone can point me to a reference that refutes this widely held notion.

David Foster Wallace, a writer of extreme talent, took his own life on September 12th, 2008. I have written several short pieces about him in the past (Death of a Genius, DFW memorial, David Foster Wallace: brain and information). Part of the sadness of his loss was he would not be sharing his mind, this thoughts, with us anymore, and for that the world has truly lost something of value.

Recently, the news flash came out that David Foster Wallace (DFW) unfinished novel, ‘The Pale King’,  would be published in 2010.

The publisher said in the NY times article:

“..that it will release the book, which runs “several hundred thousand words,” along with “notes, outlines and other material…”

The news left with me mixed feelings. On one hand I am selfishly eager to read the novel he has been working on for just over 10 years, on the other hand I am sad that depression, and his subsequent suicide, robbed the world of the completed novel he would have wanted to given to us, sad that life was so terrible for him that he took his own life, sad to think of anyone feeling that horrendous.

A good deal of DFW coverage, including all the news about his new novel, can be found at The Howling Fantods. From one of their most recent updates on The Pale King, from Little Brown and Company press release (publisher of the novel):

Michael Pietsch, Wallace’s longtime editor, said, “The Pale King is an astonishment. It is David  Wallace’s effort to weave a novel out of life’s dark matter: boredom, banality, the ‘irrelevant complexity’ of everyday life, all the maddening stuff that stands between us and the rest of the world and through which we have to travel to arrive at joy. This was as ambitious as anything he ever did, a novel that attempts to move readers deeply and help them live their lives.”

The New Yorker published excerpts from DFW’s new novel, along with the story behind his unfinshed novel, appropriately titled, unfinished. In addition, The New Yorker also posted a few pages of DFW’s writing, complete with hand written notes and editing, along with a few art pieces done by his wife, Karen Green.

Karen’s piece, ‘Hard to Fill’ is below (DFW’s boots).

Here is one page from DFW unfinished novel:

In my opinion DFW gave us the highest form of story telling.

Depression robbed DFW of his life, and took away from all of us something special. My hope is we can do something to reduce the tragic loss of lost years, and life, brought upon by depression.

From the end of the D. T. Max article in the New Yorker:

In his final hours, he had tidied up the manuscript so that his wife could find it. Below it, around it, inside his two computers, on old floppy disks in his drawers were hundreds of other pages—drafts, character sketches, notes to himself, fragments that had evaded his attempt to integrate them into the novel. This was his effort to show the world what it was to be “a fucking human being.” He had not completed it to his satisfaction. This was not an ending anyone would have wanted for him, but it was the ending he chose.


Feb 23
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Many of us drink coffee, but worry that we might be harming ourselves. While nothing is carved in stone, there is research that suggest that coffee drinking will reduce suicides and heart disease (but read the whole piece to get the full J curve story).

I was going to blog about a resveratrol alternative to increase your life span today - but with a new paper coming out on coffee I decided that it might be more important, and might do more real world ood (but tune in tomorrow for the resveratrol alternative story).

Cardiovascular / Heart disease and coffee:

The new paper (hat tip to futurepundit) Lopez-Garcia et. al., 2009 followed over 83,000 women over 24 years and studied the risk of stroke in this group. They found that women consuming coffee had a lower risk of stroke. Those that consumed about 1 cup per day had a 12% reduction in risk for stroke, 2-3 cups/day had a 19% reduction, and those that consumed 4 or come cups a day had a 20% reduction.

In men (Kleemola et al., 2000) the highest incidence of heart disease (myocardial infarction) was in those that drank no coffee (study include more than 20,000 age 30-59). Coffee consumption reduced the risk of heart disease - but only in those men who did not smoke. But for those men that smoked high coffee consumption increased risk of heart disease. But we all know that you shouldn’t smoke, but definitely don’t smoke and drink coffee. In general, for men the biggest reduction in heart disease induced death was in the moderate coffee (1-3 cups a day) consumption group (U shape curve). In this study, for women increased consumption of coffee was correlated with reduction in both death by heart disease but also all causes of death  - wow! (the more coffee the better - but see below).

More papers that see the same trends as above: Greenberg et. al., 2008, Wu et. al, 2008.

Note: there is still debate going on about the possible negative acute effect of coffee consumption versus long-term positive effects (Riksen et. al., 2008).

Researchers found similar results with teas (both green and black). Arab et. al., 2009 did a meta-analysis of all the human clinical and observations studies. In total there were data from 194,965 individuals and they found that those that consumed 3 or more cups of tea had a 21% lower risk of stroke.

Coffee consumption and risk of suicide:

Depression is a serious problem (see my piece on the personal and societal cost of depression) that too often leads to the tragedy of suicide.

In a 1996 study (Kawachi et. al., 1996) researchers followed 86,626 registered female nurses (age 34 - 59) over a ten year period. After controlling for several variables they found that those that drank 2-3 cups a day had a a 66% reduction in suicide, and there was a 58% reduction in those that drank 4 or more cups a day (hat tip to drinkingcoffeeallthetime - as she wrote her piece honoring David Foster Wallace and pointing out the reduction of suicide with coffee intake).

Not so quick as we look at the J curve: A sweet spot of coffee consumption.

A followup study (Tanskanen et. al., 2000) looked at things a bit more closely and found you have to be careful at the high end of coffee consumption. They followed over 43,000 subjects (both males and females) for just over an average of 14 years. 2-3 cups a day of coffee correlated with a reduced risk of suicide by around 34%, and 4-5 cups reduced it by around 18%. However, for those that drank 8 or more cups of coffee there was a 58% increase risk of suicide, compared to moderate coffee drinker. Hence, the J curve, a moderate amount of coffee reduces the risk of suicide (bottom of the J - better than the beginning of the J), but too much coffee is the worse scenario - the highest risk of sucide.

Bonus: According to a recent review (Nkondjok 2008, Cancer Letters) overall coffee appears to reduce the risk of cancer.

Take home message:

Go out there and enjoy your cups of coffee - but try to limit your intake to 2-3 per day for men, and possibly slightly more for women - and reduce your risk of suicide and heart disease/stroke (and possibly cancer). And of course don’t smoke. But always keep your eyes open for any drug/treatment - including ones you don’t think of as a drug like coffee, for a J curve, or a U curve (or inverted U). It is all about dosing - don’t get up to the 8 cup range (and remember to include ALL caffeinated beverages when you are calculating your daily total).

Heck - when you sum it all up coffee might be a longevity treatment that results in the coffee drinker living longer - since it reduces the leading cause of death (cardiovascular: #1 is heart disease, # 3 stroke), potentially the # 2 killer - cancer, and the # 11 suicide. And I didn’t have time to cover coffee’s positive effects on some of the others like diabetes (# 6)  and Alzheimer’s disease (# 7).

Enjoy your coffee today.

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