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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 17

I have written several pieces on depression and antidepressants (what depression feels like, depression life span and lost years, do antipsychotics and antidepressants work because they make you hungry, social isolation what happens to the brain, most common brain hack - antidepressants). As with many health science subjects trying to figure out the truth is difficult. Scientists can sit down and in a detached manner argue and ponder their points regarding if antidepressants really work - or is it all a placebo effect. However, the people with depression have to make the real world decision to take them or not. I don’t know enough about this subject to really offer enough information.

However, over at Neuroskeptic I found a very balanced view of antidepressants.

Opinions about antidepressants are polarized - most people either firmly believe that they do work, or firmly believe that they don’t. Yet neither of these positions seems to me to be supported by the evidence available. I don’t think that anyone ought to firmly believe anything about these drugs - except that better research is urgently needed.

He goes on to talk about antidepressant studies:

The issue is not a lack of studies. After fifty years of research, and untold millions of research dollars, there are hundreds of published clinical trials of antidepressants. It’s when you try to make sense of the results of this great mass of trials that the problems become apparent.

If you are at all interested in this subject matter please go read Neuroskeptic’s complete post (he is skeptical but rationale). I would have quoted more of this blog piece, but to do it justice I would need to pretty well copy the whole blog piece - so just hop over there and read it instead.

It is not a simple story, but I guess that is why there is controversy and confusion. The piece might not be able to give you a final answer, but at least you will be more informed.

Bonus:

Also check out Neuroskeptic’s what’s the best antidepressant as he discusses a recent meta-analysis study that appeared in Lancet (Cipriani et al., 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.

Feb 16

Probably most of you could name the top 10 leading causes of death (in developed countries) and I think I have even mentioned them in a blog piece - but can you name # 11?

Suicide, induced by depression is the 11th leading cause of death (2/3 of the suicides are done by depressed patients - Cassano and Fava 2002). Many times if you don’t make it into the top 10 you are forgotten about, ignored - much like Google search results.

Maybe we should pay more attention. If a brain hack (treatment) can be developed to reduce depression and suicide the world would be a better place.

Major depressive disorder (aka: clinical depression, major depression, unipolar depression, or unipolar disorder (as defined by wiki):

is a mental disorder characterized by a pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities.

Depression cost to the individual:

Major depressive disorder (MDD) over a lifetime effects 13.3 - 17.1 % of USA and Europe  citizens (Cassano and Fava 2002). The prevalence of the disorder at any one time is in the range of 2.3 to 4.9% of the population. Approximately 20% of people with recurrent depression attempt suicide. Suicide, as mentioned above is the 11th leading cause of death and represents 1.3% of all deaths (diseases of the heart 26.6%, cancer 22.8%). And you might say 1% is not much - but there is also the number of lost years due to the disease (see below). People living with depression are not usually functioning at their normal level - and hence lose many years of ‘life’.

Depression cost to society:

In the USA depression cost society 43.7 billion dollars (Cassano and Fava 2002) (could be higher now).  1.5 million disability-adjusted life years are lost each year in the world (based on 1990 data). This measurement could be put in both the individual and society cost category.

In a more recent paper (Lopez et. al., 2006) they defined burden of disease by this criteria:

disability-adjusted life years (DALYs)—to quantify the burden of diseases,
injuries, and risk factors with a single currency based on
years of life lost due to premature mortality (YLL) and
years of life lived in less than full health.

Using this criteria depression is the 3rd largest disease burden in high income countries and the 7th leading disease burden in low and middle income countries. So know depression has gone from # 11 to # 3. A 3rd entry of a Google search would get noticed.

Depression reduces lifespan beyond just suicide:

Beyond the obvious and tragic increase in the loss of life by suicide in depressed patients there appears to be additional health complications. The risk of dying from cardiac mortality is 1.5 to 3.9 fold higher in depressed patients (without prior cardiac disease) compared to the general population (Pennix et. al., 2001).

In reality, when you look at all causes of death in people with depression the risk of death is increased to around 1.3 (1.0 being baseline control) (Egede et. al., 2005) (some studies find higher numbers, other find roughly the same). And it was even worse if you had depression and diabetes.

And there is a growing recognition that there is a link between depression and both diabetes and metabolic syndrome (Dunbar et. al., 2008). Who knows which way the causal arrow points - it could even be bidirectional in this case. There is even a paper that wonders if depression should be reclassified as metabolic syndrome II (McIntyre et. al., 2007).

Take home message:

Depression is the 3rd highest disease burden in developed countries - with a very high personal and societal cost.

What ever the underlying biology (which we will continue to study) - people with major depression suffer greatly and far too many of them die from suicide and other causes of death (underlying biology of depression may contribute to both).

Depression, beyond suicide appears to increase all causes of death - but we don’t really understand why or how? There are some hints regarding the relationship between depression and metabolic syndrome/diabetes - but this needs to further studied.

Can we do anything to help these people? There are the standard treatments (wiki entry) but I hope that advances are made in the very near future to bring a better life to the large numbers of people suffering from depression.

Does the link between depression and metabolic syndrome/diabetes offer any hints of future research directions? We will have to wait and see if enough researchers are willing to explore this link further.

To saving lives and lost years.

Also see:

Do antidepressants just make you hungry?

Brain hack for happiness and better personal economics

Social isolation and what happens to the brain

Does increased socialness interaction improve health

Antidepressants do the increase or decrease lifespan

Is the glass half full or half empty

Most common brain hack: antidepressants

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