1. THE CONTROVERSY ABOUT ANTIDEPRESSANTS
This is largely country-dependent: in some countries their use is widespread and generates little
discussion; in others, many factors contribute to making them practically taboo words. The country
where I live, the Netherlands, tends towards the taboo end of the spectrum. The reason has a lot
to do with the prevalent (and backwards if you ask me) Calvinist mentality. I know that in
other places, such as most of North America and Southern Europe they are much more readily
accepted. Your mileage may vary.
The controversy is typically framed in the following ways: doctors nowadays over-prescribe
antidepressants, instead of following the psychotherapy route; antidepressants are just
a ploy from the evil pharmaceutical multinationals; our societies are drifting towards
a "Brave New World" scenario where drugs are used to keep the populace happy and unable
to rebel. Well, my personal opinion is that there is some substance to some of these
worries, but they are largely exaggerated and fail to acknowledge one very important
fact: antidepressants are very effective in treating clinical depression. This is not
a matter of opinion: it has been demonstrated in several double-blind clinical trials.
First, on the issue of over-prescription. I would say that they are both over-prescribed
and under-prescribed. The problem is that most doctors do not understand depression well,
and will prescribe drugs to people whose brains are healthy, and fail to provide them
to people who could actually benefit from them. Take people who are mourning, for example.
In most cases, these people do not have a depression. Grief is something perfectly normal,
and its onset is all too sudden to cause a depression (remember that a depression typically
takes years to develop). Likewise, consider giving antidepressants to very young
people: the brain of a child or even a teenager has such a fantastic ability to repair
itself that it takes quite a pounding for a depression to develop. In these cases,
antidepressants and all their unavoidable side effects are more likely to hurt than to help.
On the other hand, there are people who have minor problems with stress and anxiety,
or whose blood pressure is above normal for no apparent reason. They are often simply
told that they should watch out for salt in their diets, or to take up yoga or meditation.
This advice might help, but only to a certain degree. I suspect that a course of an
antidepressant would have a stronger and more lasting effect.
Moving on to the subject of side-effects. Modern antidepressants are generally well-tolerated
and safe to use. They do have side-effects, which depending on the drug and the person can
be significant enough that people discontinue taking the medication. However, this is yet
another issue where proper handling by a competent professional will make a huge difference.
What one often finds is that people are given the wrong drug for their case. Imagine for example
an overweight patient being given an antidepressant which increases appetite, or someone
who has a satisfactory sex life and is given a drug which upsets their libido.
What is required is matching the profile of the patient with the expected side-effects of
the drug. Granted, there is plenty of variation among individuals, but the overall
pattern is still strong enough that we can categorically say what will be the most likely
side-effects of a given antidepressant. A straightforward discussion with a good professional
will go a long way towards finding a drug tuned to your particular case, thus minimising
the negative side-effects and decreasing the chances of premature discontinuation.
Finally on to the subject of psychotherapy. As someone who had a depression, I can assure
you that there is nothing more patronising and irritating than people who bring up
the "psychological help". A depressed person will definitely need professional help,
but mostly for a proper explanation of the problem, to learn relaxation techniques,
to know how to listen to their bodies, and to be coached in the lifestyle changes
required for giving their brains a chance to recover.
Once they are recovered, perhaps some therapy might be needed to make sure
that whatever behavioural patterns which contributed to the development of the illness
will not recur. However, and I cannot stress this enough, therapy is not a
substitute for medication, and "psychological help" is a misunderstanding.
Suicide is an unavoidable part of depression, and one which better than no other
embodies all the prejudice, the misunderstandings, and the narrow-minded attitudes
towards the illness. How often does not one hear pompous proclamations about
the cowardice of suicide? Or the patronising and delusive belief that with
the proper arguments one can convince a depressed person that life is worth
Here I speak only of suicide in the context of a clinical depression. Obviously,
non-depressed people can also commit suicide (think of a suddenly dispossessed
rich man, or a politician irreparably stained by scandal), but the point I will
try to carry across is that suicide associated with depression is a different
beast altogether. Again, forget psychology and try to understand the problem
from a physiological perspective.
Remember that a depression affects the part of the brain responsible, among other
tasks, for planning. During the critical stage of a depression, the brain
is in such a condition that a person cannot even visualise a future without
the despair and the suffering. They cannot even plan their way out of bed,
for that matter. And remember that the reason is entirely endogenous and
physiological: there is no amount of well-intentioned arguments which will
change that . Also, do not think that you can imagine what it feels like.
You cannot. I have been there and I can no longer imagine it.
Bear also in mind that during the critical stage of a depression, people
experience anxiety crises of such magnitude that they often resort to
self-mutilation to try to quench the suffering. Again, do not think
that you can imagine what it feels like. It is most likely that you
cannot. An anxiety crisis alone can drive a person to commit suicide.
"Suicide is a permanent solution to a temporary problem". There is much
wisdom to this sentence, and it is probably the best advice you can give
a depressed person. Unfortunately, during that critical stage is difficult
for them to visualise the temporary nature of the problem, and suicide
is not uncommon. If you a have a friend or a loved one going through
that stage of a depression, do take the possibility seriously and do
what you can to prevent it from happening. In particular, make sure
they are being handled by a competent professional. Fortunately, especially if
people are young, this stage will not last very long, typically just a few
days or weeks.
To conclude, if you never had a depression, and should you feel inclined to make
grandiose pronouncements on suicide, bear in mind that you have no clue whatsoever
of what you are talking about.
3. THE ROLE OF SPORTS
The role played by sports and physical exercise in depression is far more complex than either
the "sports good" and "sports bad" mantras would lead one to assume. Moreover,
I would say that this is one area where our current understanding of depression is sorely
incomplete. Consequently, beware that much of the material in this section is conjectural.
I am well aware that most people's gut reaction will be to dismiss my conjectures as pure rubbish,
since "everyone knows that sports are good for you". A couple of years ago I would have
whole-heartedly agreed with them, but I have learnt otherwise in the meantime. Furthermore,
read carefully and you will see that I do not deny that sports can be good for you. I simply
add a poignant "however" to the issue of sports and depression.
This issue is complex enough to warrant a number of subsections. I will first make
a distinction between the temporary improvement of mood brought by sports, versus
the long-term actual improvement of the depression. Second, I will put forth the
tentative mechanism of why moderate amounts of exercise can help to recover from
depression. Third, I will describe the caveats of doing exercise to recover from
a depression. At last, I will describe a real-world example of how sports can be
used to make people be more active during a depression, with the drawback that
recovery takes longer.
3.1. Feeling Good vs. Actual Improvement
"Sports alone can lift up a depression", says one of the most common advice about
the illness. Unfortunately, this statement is grossly incomplete, often tragically so. If you
have properly understood the roles played by adrenaline and cortisol (take a look again at
Section 2.2 of the first part of this series to refresh your memory), you already have a glimpse
of why this is such misleading advice. Exercise can indeed momentarily lift up the
subjective feeling of a depressed person, but that is all caused by adrenaline. It is
therefore critical to make the distinction between the momentary mood improvement caused
by exercise (which is undisputed), and whether it translates into an actual improvement
of the underlying depression.
Please refer back to Section 2.2 of Part I. There I have speculated on recent findings
which indicate that a process known as neurogenesis ("neuron birth") is implicated
in recovery from depression. This process takes about three weeks to occur, which also
happens to be the average time required for antidepressants to have an effect. This
coincidence has led some to hypothesise that antidepressants work by stimulating neurogenesis
. The point of this digression is to emphasise that anything which has
a positive effect on recovery from depression is likely to require the same three weeks to work.
One should therefore be a bit suspicious of any cure which seems to work instantly, as is the
case of exercise.
Now the question is: does exercise also have a long-term positive effect on depression,
or is it all a short-term illusion?
3.2. Why Moderate Exercise May Sometimes Help
I will now speculate on two hypotheses why moderate amounts of
aerobic exercise seem to help mildly depressed or healthy individuals.
(To be more precise, what is usually prescribed is a moderate aerobic exercise lasting
for about 45 minutes, and taking place 3/4 times per week. By moderate
it is implied that the heart rate never rises past 100-120 beats per minute, depending
on the age).
To understand the first hypothesis, you must first take a look at what aerobic exercise really is.
If you consider the body's response to exercise, it looks exactly like the effects of an extreme,
short-lived stressor: heart rate goes up, senses become sharper, sweat is intense, etc.
How can an intense stress prevent stress? The answer may lie in a phenomenon called
In brief, short-lived stressors might trigger the repair mechanisms of the body to overcompensate.
This phenomenon has also been reported in other contexts. We all know about the health damage
caused by radiation. However, people subjected to artificial zero radiation environments will
get sick. Since our bodies have evolved in an environment with naturally occurring low-levels
of radiation, our cellular repair mechanisms are used to that soft but constant radiation damage.
Amount of stressor
Figure 1: The hormetic response curve. Note how small amounts of the stressor event
have a positive effect, but which decreases rapidly as the amount increases. Large amounts will
actually have a negative effect on the body. (The stressor event can be exercise, radiation,
or any other agent for which there is a hormetic response).
Figure 1 illustrates the benefit one can expect from exercise. The most important thing
to realise is that even though a bit of exercise helps a bit, that does not translate
into a lot exercise helping a lot. Quite on the contrary.
At this point you might be wondering about the location of two very important points
in the graph: the first is the amount of exercise which provides the highest benefit;
the second is the amount where the transition from positive to negative effect happens.
Well, the truth is that these points are not fixed and depend (among other factors)
on how serious the depression is. To understand why, you must take a look at Figure
3 from Part I, and remember that the more serious the depression, the longer it
takes for the body to recover from any influx of adrenaline. For a person with
a serious depression, even exercise which a healthy individual would describe
as "moderate" will require a long recovery time. So long in fact that it would
have a negative effect on sleep. In a sense, the more depressed you are, the
more compressed on the x-axis is the graph in Figure 1.
| / \
| _/ \_
| / \
| / \
Figure 2: The hormetic response curve for a severely depressed individual
and for a healthy one.
You may now begin to understand why I advise caution in regard with depression and exercise.
For a severely depressed individual, the graph is so skewed towards the left that any
exercise beyond a 30 minute gentle walk in the mornings is discouraged. As the recovery
progresses, the graph expands on the x-axis (see Figure 2), meaning that people are able to
safely do more physical activity and for longer. In the case of a healthy individual or one with
a mild depression, the graph is significantly expanded on the x-axis, meaning that moderate
exercise as a way of treating depression is a viable option. (Again, moderation is the key!)
The second hypothesis is more straightforward. Regular exercise improves the condition
of the cardiovascular system, thus making it less likely to go into emergency mode
whenever physical requirements increase, and therefore reducing the amount of adrenaline
that needs to be put into the system. However, and in similarity with hormesis,
the advantages from exercise probably only outweigh its disadvantages for healthy
individuals or mildly depressed ones.
At last, a word of advice. If you think you have a depression, you should seek professional
help. It might be tempting for some people to try to exercise their way out of a depression,
but chances are you might actually be making your condition worse. See next section for details.
3.3. Caveats of Treating Depression With Exercise
Looking back on Figure 2 from Part I, some people might suggest that a person with a severe
depression could avoid the crashing down simply by exercising every single day.
In a sense, as soon as your body begins to crash, you simply do more exercise to rev it
up again. You could therefore rip the positive temporary effects of exercise, and hopefully
avoid the negative side. This routine "sort of" works, but is also extremely dangerous,
as I will proceed to explain.
The major problem is that having too many stress hormones flowing through veins has a
negative effect on sleep. And sleep is crucial for recovery. So people with more
severe depressions who exercise every day will not sleep as much as they should,
and the recovery will therefore take longer (see next section for a real world example).
More seriously, if the amount of
exercise is too high, they might even regress. Even more seriously, if the underlying
depression worsens, people might be tempted to increase the amount of exercise
to compensate, which will quickly lead them into a very dangerous downwards spiral.
In a sense, advising a seriously depressed person to exercise is like telling a drunken
individual that the best way to avoid a hangover is to keep drinking; or advising a heroin
addict that the best way to avoid the withdrawal symptoms is to keep injecting the drug.
This is unfortunately not widely known, but even healthy individuals who exercise
too much can develop the symptoms of a depression. This is sometimes referred
to as the athletic overtraining syndrome , and by now
you should have understood the basic mechanism of why it arises.
3.4. A Real World Example
At last I will provide you a real world example which illustrates the caveats
of doing sports during depression. Some companies here in the Netherlands
rely on a sports-intensive routine to put people back to work sooner. In basic terms,
the routine involves running every single morning for a period between one hour and one
hour and a half. The running is performed under controlled conditions, to prevent
the heart rate from ever going over 130 beats per minute. If you understood the role
of sports in depression, you will also realise just how this scheme works: it
basically gets their brains running on adrenaline. This is not entirely harmless,
as during the recovery period the people will have elevated heart rate and stress hormones
flowing through their veins. Also, with all that adrenaline
in their systems, they will not sleep as much as they could, which makes a full
recovery last much longer, up to three years.
The advantage of this scheme? Well, they do begin working (part-time of course)
much sooner than otherwise.
At this point you might be wondering how they do not realise what is really happening.
Remember that adrenaline is an insidious hormone, which makes one feel good even
as it revs up the body, and this scheme requires them to exercise every single day without exception.
Obviously, the idea is to keep them from crashing down from all that adrenaline, and therefore to
prevent them from realising their true status. Also, there is widespread ignorance
about depression among dutch GPs, which makes it all the more unlikely that
someone will realise that there is something fishy going on. Personally, I find
this scheme to be utterly mad. But then, I am not a Calvinist.
Should you be thinking that this scheme is also a perfectly viable alternative way of curing
a depression---one which takes longer, is potentially harmful to the general health, but
does allow one to become active sooner rather than later---I would even be tempted to agree
with you. However, I still think that the ultimate choice should reside
with each individual person. It is their health we are talking about, after all. These
people should be properly informed of all possible alternatives and the implications of
each one. This is currently not happening.
4. DEPRESSION AND AGEING
You do not see 60-year olds having the same lifestyle as 20-year olds. Even a 40 or a 30-year
old probably would not be able to accommodate for a long time all the intense living and partying
of their youth. We naturally accept that our physical abilities decrease slowly with age, and
our brains are no different. Mind you, in this context I will speak only of the brain's endurance,
not of the general cognitive abilities. Therefore, do not interpret the graph in Figure 3
as "getting dumber with age". (Though it is most likely that cognitive abilities also decrease
with age. Luckily, the added experience can in large part compensate for that).
Figure 3: The maximum normal capacity naturally decreases with age.
Bear in mind that I am largely speculating here, but I would not be surprised if the reason
why depression tends to strike first towards the mid 20s (and this is a fact) is related to a dip
in the maximum normal capacity which happens after adolescence. Many people simply fail
to accommodate for the necessary changes in their lifestyle, and thus find themselves
constantly going over their (now slightly diminished) limits.
Still on the speculation front, consider the fact that people tend to sleep less as they get older.
Could it be related with the graph in Figure 3? If sleep is indeed fundamental for the brain to
repair itself, and if age cuts down the requirements for the maximum normal capacity, it is not
too far-fetched to imagine that people would therefore require less sleep as they get older.
Speculations aside, do not look with gloom at the graph. Ageing is not a death sentence
as far as feeling well is concerned. People do generally accommodate by making changes
to their lifestyle, and remember that depression only arises should you constantly go
over your limits. Furthermore, in percentage terms, the natural decrease might not
even be large. (Unfortunately, our current understanding of depression does not yet
allow us to make precise quantifications. See Section 7 for details).
5. THE GENETIC LINK
I have not brought up the genetic link up till now, but it is without doubt one of the
primary risk factors. Depression seems to run in families, and even after the environmental
effects are taken into account, the genetic link is still clearly there .
Some studies have shown that approximately one out of every three people have a genetic
predisposition to develop a depression. However, like in many other
cases, the interplay between genes and environment is also relevant for depression:
only about half of those with the genetic predisposition will actually develop the
In any case, should you have cases of depression among close blood relatives, do take it as
a warning that you too might be at risk.
Note: A person is most closely related to their siblings, their parents, and their children.
In either case, you share with them approximately 50% of your genes (for which there is variance among the breeding population).
Grandparents, grandchildren, aunts, uncles, nephews, and nieces are next: the shared portion is approximately 25%.
In these cases, the conditional probability of having a depression knowing that your relative had a depression
is higher than the above mentioned absolute probability of about one third.
For relatives farther beyond the genetic proximity measure (cousins, etc), the conditional probability approaches
the absolute probability for the general population, and is therefore not quite as relevant as an indicator.
6. IS DEPRESSION ON THE RISE?
Is the incidence of depression really on the rise? Statistics seem to point that way ,
and considering the risk factors, that should not be altogether surprising. The truth
is that many modern hobbies are actually very demanding on the brain. Should a person
pull long hours at work and then come home to face an equally demanding hobby, there
is a very good chance that they are pushing the brain past its limit.
This is likely to strike a chord with the Kuro5hin crowd: surfing the web and blogging
should be seen as work as far as the brain is concerned. In a similar note,
information overload is not just a fancy buzzword: it is a factor contributing
to the development of depression. The list is long: mobile phones, news tickers,
instant messaging, etc. We seem to be very good at devising ways to overload our brains.
On a more positive note, if one considers the current understanding of the problem, plus
the available means to treat it, making serious clinical depression a thing of the past
is well within our reach. What is required? Just getting the message across! Sadly,
it may prove difficult to overcome centuries of prejudice surrounding mental illness.
7. QUANTIFYING DEPRESSION
You will certainly have noticed the lack of scale in all the graphs herein shown. The truth
is that research into depression has not yet reached the quantification stage. This is a pity,
as much of the prejudice (especially in getting official recognition for the problem) could
be avoided if there were tests which could estimate the seriousness of a depression. Which
is not to say that such tests are not possible. In fact, in this section I intend to propose
the means by which they could be developed.
At this point you might be thinking that blood pressure already provides a fine estimation.
This is only partially true. Foremost, several factors other than stress levels have an effect on
blood pressure. Furthermore, blood pressure is a static measure, unable to differentiate
between the state of deep depression / low activity and the state of
mild depression / high activity. This is an especially crucial distinction in the
recovery phase of a depression. (Blood pressure is more reliable during the buildup phase
towards a depression precisely because the activity variable tends to be always high,
as people struggle to maintain a normal lifestyle).
My suggested test also relies on blood pressure, but adds a dynamic measure of that variable.
In short, the idea is to build a graph showing how blood pressure progresses with time as
the test subject performs a high-concentration activity. Figure 4 shows what one would
be likely to expect from a healthy individual, a mildly depressed one, and one more deeply
Figure 4: The blood pressure response curve for three individuals
with varying degrees of a depression.
Note that a depressed individual will typically not only have a higher blood pressure
at rest, but more importantly, a steeper response curve. This could be the basis
for developing an objective test of the seriousness of a depression. It would also
be extremely valuable for tracking the progress of the illness.
The test activity is an open question. I would suggest a test which would require
both high concentration and short-term memory. In my personal experience, I noticed
that the simple game "Concentration" (the one where you are supposed to pick pairs of cards
out of a large set of unturned cards ) provokes an almost immediate response. It might
be a good candidate for the test.
Obviously, there is a fair amount of noise which makes a precise measurement harder.
How well the test subject slept the night before is one variable hard to control.
Likewise for the degree to which they are enjoying the activity. Furthermore, other
variables such as current medication and time of day would also interfere.
Another advantage of an objective test would be an estimation of how much time would
be required until the test subject could be considered cured. I realise that there
are several factors interfering with the progress of the illness, but given a large
population of test subjects, one could compensate for factors such as age. It is
only a matter of statistics, after all. In any case, a rough estimation is a lot
better than no estimation at all.
At last, one small note of hope: there is research underway which uses imaging techniques
such as fMRI to look directly into the brain and see the changes caused by depression .
Unfortunately, it might take quite a long time before such research is put into practical use.
The test I proposed is low-tech, potentially a lot cheaper, and could be developed immediately.
8. THE BURNOUT SYNDROME
There is much talk (at least in the Netherlands) about the so-called burnout syndrome.
And as is often the case, there is more noise than signal in this discussion. First of all,
in medical terms, there is no such thing as a burnout. There are depressions, period.
A burnout is just a depression whose causes are mostly work related. Remember
that the person's attitude towards the task at hand plays an important role in the
biochemistry of the brain. Should you have a job that you find boring and repetitive,
or should the surrounding circumstances (overbearing boss, bad corridor atmosphere)
make you feel uncomfortable about going to work every day, a depression is likely
Second, when a person is said to be burned out, what they have is a lingering
depression from which they have not yet fully recovered. Also, there are plenty of mildly
burned out individuals who have never received any kind of treatment. They often
drone through life for years before the problem is diagnosed.
I made a section out of this issue precisely because the general attitude in this country
is to dismiss burnout as just a psychological problem, thus being handled with
a lot of complacency, or just ignored. This is all the more tragic if one considers the
statistics which show the Netherlands to have some of the highest percentages of people
affected by this problem. There is indisputably also a psychological component to
burnout, but it goes far deeper than that.
This section is dedicated to my nihilist friends who thought I have been exaggerating
by equating a healthy brain with happiness. In truth, having a healthy brain and no
symptoms of a physical depression does not mean your life will be a carnival of constant
bliss. There are people who are unhappy their entire lives and yet never develop
a depression. They have a general discontent with life, a permanent feeling that
the present is not satisfactory enough, and frequent bouts of the blues.
However, given that their brains are healthy, they are capable of feeling happiness
when circumstances are favourable. In comparison, a clinically depressed person will not feel
happy even if all their problems were magically resolved. If you have not done so before,
you will now understand how critical it is to make a distinction between the psychological
feeling which could be described as "depressed", and the physical illness which affects
the brain---clinical depression. Many a prejudice would be overcome if healthy individuals
could be made to experience, even if just for just five minutes, what the fire and
the desperation of depression feel like.
10. FACING THE PREJUDICE
Most of the advice contained in both instalments of this document is based on one very important
assumption: society will give you the means to recover. Unfortunately, this is still far
from being the case. A seriously depressed person cannot constantly go over their
limits if their brains are to be given any chance of recovering. Take the practical example
of restarting work: one has to build up the activity slowly, in accordance with the increase
of the maximum capacity of the brain (remember Figure 6 from Part I). Obviously, this requires
some sort of official recognition of the particularities of depression. In theory, this is part
of the law and recognised in most civilised countries. In practise, things can be very different.
Do not assume that because you live in an otherwise tolerant and socially-minded society,
depression will also be well understood. Bear in mind that other factors come into play,
most importantly the fact that cure takes a long time, which means it
is also very expensive for an employer. Also, the overall stance towards mental illness
might be biased by the prevailing religious substrate, influencing attitudes even of
non-religious people: take the example of Calvinism here in the Netherlands.
All in all, when depression is the subject, do not be surprised when society shows its ugly side.
The good old advice of stashing away some six-months worth of salary for a rainy day is
very much applicable in the case of depression: you will need it.
Interestingly enough, I see no reason---other than prejudice and bad will---why the state
of affairs should remain like this. Take again a look at Section 7: it is well within
our means to devise reliable objective tests to assess the seriousness of a depression
and/or to determine when a person is again fit enough to work.
Depression itself provides more than enough misery. It is inhumane and cruel
that the problem should be compounded by lack of recognition.
 Why? The Neuroscience of Suicide
 Nietzsche's Toxicology
 Taming Stress
 Wikipedia: Clinical depression
 Wikipedia: Concentration (game)
 Wikipedia: Functional magnetic resonance imaging
 Depression and the Birth and Death of Brain Cells