
Toward a Predictive Theory of Depression - mpweiher
http://slatestarcodex.com/2017/09/12/toward-a-predictive-theory-of-depression/
======
cassowary37
Professor of psychiatry here - I've spent the past 20 years trying to help
folks with depression, and related illnesses, and trying to study these
diseases at a genetic level. I suspect this will get me down-voted as I know
the medical/biological perspective is often unwelcome on hn. However: a key
error people make here and elsewhere in speculating about depression (and
suicide, and ADHD, and...) is either extrapolating only from their own
experience, or from a vastly oversimplified psychology 101 perspective. For
example: "Depressed people move more slowly, in a characteristic pattern
called “psychomotor retardation”. Well, yes - except when they have agitated
depression, characterized by psychomotor restlessness. Or, when they have
neither of these. Likewise, oversimplifying by claiming it is a disease of
dopamine, or serotonin, doesn't much help. When my car stops working, is it a
disease of gasoline? Part of the challenge of depression is its very
heterogeneity. What we need is not more theorizing, it is more recognition
that we need better treatments of all sorts.

~~~
empath75
I’ve never been sure why it’s treated as a disease rather than a symptom. It’s
like saying someone with a high temperature is suffering from fever. Which is
nice and descriptive and treatable with the right medications, but does
nothing to describe the underlying cause.

~~~
quantumhobbit
Lots of what we now consider symptoms were thought of as diseases until the
underlying problem was better understood. It wasn’t that long ago that your
fever example was how people thought. The fever was the disease regardless of
the unknown underlying cause.

That depression is considered a disease by itself and not a symptom of many,
possibly related, problems suggests how little we understand it.

------
themodelplumber
It's a weird coincidence to read this. I was doing basic research on
depression and saw that dopamine played a role in helping people feel good.
One WikiHow article [0] later, I had an idea: Start reaching goals. I started
very small, like taking progressively longer walks.

Since that time I have earned something like five different certificates in
various areas of interest (ARRL coming up next) and as a very recent
development, completed my university degree after 15 years of delay due to,
among other things, depression.

I find that depression can still affect me, but the episodes don't last as
long (around 2h max, lately) and I have a bunch of tools for dealing with
them.

[0] [http://m.wikihow.com/Increase-Dopamine](http://m.wikihow.com/Increase-
Dopamine)

~~~
davymac
This works very well for low-grade depression for sure. There seems to be a
threshold where this type of intervention becomes completely ineffective
(personal experience).

~~~
themodelplumber
I agree. From keeping logs over the last few years, severe depression was more
likely to occur due to e.g. not enough sleep or just illness, and in those
cases accomplishments were impossible. Rest was it, and I felt lucky if I
could get good rest before acting on any depressing thoughts or ruminations.
So I wouldn't call goal-reaching a standalone cure; far from it. Also there's
the fact that people accept/reject potentially helpful information based on
different criteria, from very rational (is it in a reputable journal) to
irrational (do I like the person who gave the information) to incredibly
subjective (did I think of it on my own?). So the idea of "why not try
accomplishment" may be doomed from the start, due to factors outside of the
advisor's control.

~~~
davymac
I noticed that rest only somewhat helped, but was significantly more effective
if absent of any worry of external responsibilities. E.g. If I took vacation
from work and didn’t tell my girlfriend about it so she wouldn’t worry about
me and text me incessantly... I could turn off the thoughts/worries of the
outside world completely for a few days and that made a pretty dramatic
difference. I didn’t cure me at all, but it took me out of the really
dangerous zone after about 2 days. Also, sleeping in a hammock, haha. So much
better than breathing stale air for 2 days.

This is more circumstantial however, as my trigger at the time was
accumulating too many perceived responsibilities and fearing failure. To be
honest I feel the triggers are nearly irrelevant, but removing myself from
them gives me enough temporary relief for my body to get out of stress mode.
Which in turn removes some of the depressive overhead to give myself a golden
window of opportunity.

------
tcj_phx
> Depressed people move more slowly, in a characteristic pattern called
> “psychomotor retardation”. They display perceptual abnormalities. They’re
> more likely to get sick. There are lots of results like this.

> Depression has to be about something more than just beliefs; it has to be
> something fundamental to the nervous system.

Depression is frequently related to metabolic problems: people are exhausted
because their mitochondria aren't putting out enough ATP to run their nervous
system.

There are various interventions that can help. B-vitamins are important
cofactors for burning sugar to make energy. T4 thyroid is activated by the
liver to make T3, which is one factor that boosts the metabolism. If the liver
is overworked (alcohol, drugs, hormonal imbalance, too much pufa, etc), it can
have trouble activating adequate thyroid.

Emotional resiliency is a big factor here too. My friend was really just
lonely before she met me. She's doing better now because she now has a
'vision' for her future (she originally 'lost her future' when she was
expelled from high school, essentially for being depressed and self-medicating
with drugs that are now being investigated for treating depression).

~~~
bluntfang
there's a difference between doing a bunch of molly every weekend for fun and
self medicating.

~~~
sixo
There is, it's usually pretty easy to tell the difference. Doubt anyone would
mistake them, and I doubt the OP is.

~~~
tcj_phx
> There is, it's usually pretty easy to tell the difference. Doubt anyone
> would mistake them, and I doubt the OP is.

A few months ago a young man (early 20's) came into a shop I sometimes hang
out at. "What brought you to town?" "Recovery." He'd been in town for 3 weeks,
and sober for 3 weeks and 1 day.

I asked him, "People usually know when their problems when substances started,
when did it start for you?"

When he was in 3rd grade his teacher thought he was disruptive. They put him
on some kind of medication for "ADHD". He told his parents in 9th grade that
he was going to kill himself if they didn't take him off the pills. Soon after
discontinuing his "ADHD" medications was when he started experimenting with
self-medicating... Tobacco, alcohol, etc.

His latest bender was on alcohol & laughing gas (nitrous oxide [0], for the
euphoria).

[0]
[https://en.wikipedia.org/wiki/Nitrous_oxide#Recreational_use](https://en.wikipedia.org/wiki/Nitrous_oxide#Recreational_use)

After a bit I told him, "I bet you're exhausted."

"YEAH!"

"Recovery" is good for getting people to feel like failures, so I thought it'd
be helpful for putting a different 'frame' on his last 15 years. I told him
that he doesn't actually have a substance abuse problem, he's just been
exhausted this whole time, and didn't know what to do to help improve his
energy levels. I gave a few suggestions for keeping his energy levels up.

Saw him three or four more times over the next 2-3 months, and he was doing
much better. I saw him last 2 days before he returned to where he came from. I
think he's got a chance this time.

~~~
HerrFolgreich
Would you mind to elaborate a little bit on your suggestions? That is if it's
not too specific.

~~~
tcj_phx
The only thing that fellow could really do for himself was buy some coconut
oil. The brains of alcoholics become insulin-resistant and switch to running
on acetate, one of the breakdown products of ethanol. The medium-chain-
triglycerides in coconut oil provide brain cells with an alternate source of
fuel. (I understand that Coconut fatty acids are short enough to be burned
without having to go through another step that longer saturated fats [butter,
etc] require; I don't remember exactly what that step is.)

I don't think that guy was able to get the coconut oil while at the recovery
center. I think giving a more helpful context for viewing his history of
addiction was much more helpful than the recommendation for coconut oil.

Another heavy drinker I know does fine while on "vacation", but "stress" in
his every day life leads to excess drinking. I have no influence with this
one, but I'd try to get him to eat more sweets when in stressful situations -
juices/etc. I've heard an old treatment for alcohol withdrawal is to feed them
lots of sugar. Here's a random NY Times article that says sugar helps reduce
cortisol levels: [https://well.blogs.nytimes.com/2015/04/23/sugar-as-a-
stress-...](https://well.blogs.nytimes.com/2015/04/23/sugar-as-a-stress-
reliever/)

IMHO, sugar in juices and other foods is basically fine; starch is 100%
glucose and is a greater contributor to excess weight. Lots of caveats with
regards to the sugar issue...

~~~
girvo
I was a heroin addict for 6 years, and have been clean for 5. The sweets thing
was very true for most addicts I knew as well as myself: in withdrawals I’d
crave sugar something fierce. Gummy bears would temporarily make me feel
better. It was interesting.

------
Klockan
When I was depressed I had perfect trust in my ability to predict events, it
was just that no matter how much I tried I couldn't predict a future where I
weren't constantly in agony. I got over it by letting go of most things that
were hurting me like friends, family, dreams etc. So now I live a fairly
unassuming life but I am content. It might sound a bit boring but it is much
better than living in agony every day for the rest of your life.

~~~
sleepyandlazy
How did you let go? I've tried things like meditation, but it always feels
like things keep coming back.

~~~
Klockan
It wasn't something I just decided to do, 15 years of hating my life eroded
almost everything but my basic needs. Now I can look back at that time and
with confidence say 'no' when asked to do something which would cause me to
relapse.

------
Oxitendwe
What I have found through my experiences with depressed people is that the
vast majority of them are not insane people in a sane society, but perfectly
sane people in an insane society, people who have maladapted to their
environment but would otherwise (if they had a better one) be perfectly
healthy individuals. Many of them internalize their sadness and helplessness
and make it a part of their identity, further reinforcing the common belief
among depressed people that they are ill at a biological level (and are not
merely healthy people in an unhealthy environment). I don't think the solution
to this is ever going to lay in the hands of psychologists, and certainly not
psychiatrists (SSRI's and SNRI's work only slightly better than chance in most
people, and taking other antidepressant/mood-stabilizing medication is a
hellish experience all its own) - it lays in the hands of the people who
construct the environment we live in, the people in charge of its development
and health, the people who have the most power over society. These are the
people who have destroyed it and made the environment we all have to live in
such a hellish place, and their successors will certainly be the only people
who can fix it.

~~~
defined
I don't know. Depression has been recorded for thousands of years, so either
society has always been insane (quite likely), in which case it's not likely
to turn around any time soon, or there are other causes of depression. Some
people can also fall into a depression for no identifiable reason (I can vouch
for that from experience).

SSRIs and SNRIs and other medications have saved my life and some of my
sanity, and I have high confidence that it's not a placebo - for me - having
tried and failed with probably a dozen of these over the years, before hitting
on a workable combination.

And after maybe 5 years or so, that combination became ineffective, and I had
to try a few more.

But that's just me, so this is anecdata.

~~~
Oxitendwe
>I don't know. Depression has been recorded for thousands of years, so either
society has always been insane (quite likely), in which case it's not likely
to turn around any time soon, or there are other causes of depression. Some
people can also fall into a depression for no identifiable reason (I can vouch
for that from experience).

Of course there have always been depressed people, but the modern phenomenon
where supposedly 10% of the population will have it in their lives, or where
entire countries experience skyrocketing suicide rates, is certainly not
related - I find it very difficult to believe that they all have a biological
problem, instead of a cultural or societal problem.

>SSRIs and SNRIs and other medications have saved my life and some of my
sanity, and I have high confidence that it's not a placebo - for me - having
tried and failed with probably a dozen of these over the years, before hitting
on a workable combination.

I don't doubt this - I only said that the vast majority of sufferers of
depression do not seem to suffer from a biological problem. From my personal
experience, I have seen that most of the depressed people I have known have
gotten better not through medicine or medical procedure, but by consciously
trying to make their lives better and be the best person they can be.
Obviously this won't work for everyone - there really is such a thing as
biologically-caused mental illness (see: schizophrenia, for example), but I
think it is much rarer than people are willing to admit.

>But that's just me, so this is anecdata.

All data is anecdata. It's not worthless just because it happens to be your
actual life and not collated and tallied by some detached scientist, it has
meaning and value even without being a part of some anonymous dataset you can
take confidence intervals on.

~~~
defined
You make your points persuasively and elegantly, and I agree with you for the
most part. I think much of what is diagnosed as depression in recent times may
be a synonym for despair at these times (echoing Cicero : "O tempora! O
mores!"). On the other hand, clinical depression of the kind that has assailed
me since my teenage years (and from which my son suffers and showed signs of
since 5 or 6 years old) appears most certainly to be genetically caused.

I suspect that maybe a physical cause of depression is less rare than you
think.

------
hashberry
> Depression has to be about something more than just beliefs; it has to be
> something fundamental to the nervous system.

Is he saying thoughts and beliefs aren't fundamental to the nervous
system/CNS/brain?

What if people get depressed because their lives suck and they had a shitty
childhood?

Also, why are women twice as likely to get depressed than men?[0] If
"happiness is the derivative of neural confidence"... then do men have more
neural confidence?

[0] [http://www.mayoclinic.org/diseases-
conditions/depression/in-...](http://www.mayoclinic.org/diseases-
conditions/depression/in-depth/depression/art-20047725)

~~~
theptip
> What if people get depressed because their lives suck and they had a shitty
> childhood?

But people don't only get depressed because of those things; plenty of
people's "lives suck" who aren't depressed, and plenty of people with good
lives _are_ depressed.

[https://en.wikipedia.org/wiki/Major_depressive_disorder](https://en.wikipedia.org/wiki/Major_depressive_disorder)
says:

"The cause is believed to be a combination of genetic, environmental, and
psychological factors.... About 40% of the risk appears to be related to
genetics."

So yes, thoughts and beliefs are part of depression, but they certainly don't
explain all of it.

~~~
eradicatethots
Beliefs are passed down like genes.

~~~
jschwartzi
This is true in the case of my family. My brother and I learned how the world
worked from my parents, and it's taken years for me to unlearn what they
taught me instead of some actually useful beliefs.

------
Alex3917
This doesn’t make sense to me. Pretty much every purported treatment for
depression involves either increasing the amount of sensory stimulation you’re
getting or else becoming more attuned to sensory stimulation: exercise,
acupuncture, aromatherapy, drugs, meditation, float tanks, social interaction,
music, intensely flavored foods, cold therapy, saunas, electroshock therapy,
etc.

Occam’s razor would suggest its more likely that lack of sensory stimulation
causes some sort of brain damage, e.g. inflammataion or receptor density
changes, and that it just takes a few weeks to reverse. I’m not seeing what
evidence there is for this pereptual confidence model beyond what I’m
proposing. I wouldn’t doubt if people do get more confident in some aspects of
their sensory experience, but it would seem difficult to prove this as an
explanatory model.

~~~
Klockan
> exercise, acupuncture, aromatherapy, drugs, meditation, float tanks, social
> interaction, music, intensely flavored foods, cold therapy, saunas,
> electroshock therapy, etc.

None of those are guaranteed to work though, a significant number of depressed
people never gets over it and it wouldn't be that way if we knew effective
treatment methods.

~~~
trapperkeeper74
The current answer is we don’t yet have full functional pathologies of types
of depression, noninvasive, specific mood disorders classified down to exact
neurological dysfunctions, accurate and precise knowledge of how existing
antidepressants work and evidenced-based application of particular therapies
based on such scientifically-identified presentations. Clinical psychiatry has
been mostly a scattergun, guesswork that lacks scientific rigor.

For example, I just tapered-off mirtazepene as it stopped working after 9
years and, so far, bupropion isn’t helping. I’d really like to try S32212 if
it proves safe enough in human models because it likely lacks the GI and
weight-gain issues.

~~~
pault
I've tried almost every anti depressant on the market and none of them worked.
What did work for me is kratom. I've been taking it daily for about six months
and it has completely turned around my mood and general enthusiasm. There are
some minor side effects but they went away after six weeks or so. I know it
might frowned upon to recommend what is basically an opiate for depression,
but it has been a minor miracle for me.

~~~
eradicatethots
And what if your depression is cause of beliefs/behaviors and not curable with
pills?

------
trapperkeeper74
Umm, not sure this is universal but partial. Depression seems evolutionary
psych for multiple, overlapping purposes:

\- Reducing aggression (and hence conflict) in larger groups.

\- Focusing on existential re/purpose by turning inward (ie find a new
job/hobby/outlook/philosophy). Lots of reading, writing and ideation.
Hopefully rebuild confidence/positivity with completing something.

\- Retreating for terminal resource consumption minimization. Leave more for
the young.

Also, anecdotally, I did everything “right” (ie CBT, frequent vigorous
exercise, solid career, friends, sleep hygiene, address sleep apnea) and still
couldn’t escape depression’s “mind pain” and depressive state. Only medication
worked, like parting the clouds, waking up refreshed and organized thinking
instead of a jumble.

~~~
eradicatethots
Medication will stop working, it always does.

~~~
fujiters
That's the spirit!

In all seriousness, what else is there to do? Take whatever relief you can get
while you can get it.

~~~
eradicatethots
Remove bad habits/ behaviors/people... cure the problem

~~~
defined
So you are hoping there will be an ELE for the human species? Because that's
the only way your prescription is going to cure the problem on a global basis
for the foreseeable future.

~~~
eradicatethots
When I say remove I didn’t mean remove from existence lol, just from your
life. It’s true this isn’t a solution that can be implemented by governments,
it has to be implemented by the patient.

------
AnIdiotOnTheNet
>One complicating factor – how do we explain depressed people’s frequent
certainty that they’ll fail? A proper Bayesian, barred from having confident
beliefs about anything, will be maximally uncertain about whether she’ll fail
or succeed – but some depressed people have really strong opinions on this
issue. I’m not really sure about this, and admit it’s a point against this
theory. I can only appeal to the math class example again – if there was a
math class where I just had no confidence about anything I thought or said, I
would probably be pretty sure I’d fail there too.

I think the model actually fits here better than the author realizes.
Predicting failure is much safer than predicting success, it's erring on the
side of caution. If you predict that you will fail at something and prepare
for the consequences of that failure, but succeed instead, you are better off
than if you had predicted success, prepared for success, and failed. To me, it
makes sense that, when uncertain, the default would be to predict failure.

And later:

>One problem with this theory is the time course. Sure, if you’re eternally
successful, you should raise your confidence. But eternally successful people
are rarely eternally happy. If we’re thinking of happiness-as-felt-emotion,itt
seems more like they’re happy for a few hours after they win an award or make
their first million or whatever, then go back down to baseline. I’m not sure
it makes sense to start lots of new projects in the hour after you win an
award.

Wouldn't a rise in confidence have a corresponding rise in expectations? New
goals mean a return to the state of "haven't succeeded yet".

Personally I'm finding this model seems to fit better than any other model
I've heard of. Of course, I'm just some idiot on the internet, not a
psychiatrist.

~~~
pault
This sounds a lot like Martin Seligman's work.
[https://en.m.wikipedia.org/wiki/Martin_Seligman](https://en.m.wikipedia.org/wiki/Martin_Seligman)

------
whiddershins
It's great to see this here.

For context, this is the model the author is referencing:

[https://slatestarcodex.com/2017/09/05/book-review-surfing-
un...](https://slatestarcodex.com/2017/09/05/book-review-surfing-uncertainty/)

Scott Alexander is currently my favorite essayist. I just wasted most of
yesterday reading the last 18 months of his "links" posts.

I regularly pass his work on to friends and would do so more often if I didn't
think it would upset people.

------
david-cako
This particular topic is very much of interest to me; I've spent a good amount
of time thinking about how depression relates to ADHD.

Depression and ADHD are both related to dopamine and norepinephrine
dysfunction, but depression has a strong element of serotonin dysfunction as
well.

One of the defining characteristics of hyperactive individuals is their
addiction to stimulation (work, learning, leisure), which to me seems like
it's fed by negative reinforcement. Removal of these things sends them into a
depressive state because there simply isn't anything keeping them excited (and
perhaps distracted from neuroticism).

It seems like depression is kind of the contrapositive. There is the same
element of dopamine dysfunction, spawning disinterest and hopelessness, but
they lack the positive reinforcement of _anything_ to pull them out of. I
think this is where the sprinkling of serotonin dysfunction into the pie comes
in. There's a very low level of security or confidence in any sort of
endeavor.

------
icc97
I typically have odd thoughts that are often wrong. But I really like quote
from 'The Martian', "let's science the shit out of it".

I don't know if it's possible to science your way out of depression. If in
some way the curiosity gives a small enough lift to keep you getting one foot
in front of the other and learning about what's causing your depression.

It at least seems relatively risk free way of tackling depression. Learn about
the beast and track what you do and what changes your mood.

But is this something you can tell people that are seriously depressed or is
it just another useless bit of advice?

~~~
defined
> But is this something you can tell people that are seriously depressed or is
> it just another useless bit of advice?

From my point of view, it's not useful advice, partly because severe
depression utterly saps the motivation to do virtually _anything_ , and partly
because depression is highly resistant to rationality.

Mandatory references to "Hyperbole and a Half"[1][2].

[1]: [http://hyperboleandahalf.blogspot.com/2011/10/adventures-
in-...](http://hyperboleandahalf.blogspot.com/2011/10/adventures-in-
depression.html)

[2]: [http://hyperboleandahalf.blogspot.com/2013/05/depression-
par...](http://hyperboleandahalf.blogspot.com/2013/05/depression-part-
two.html)

~~~
icc97
Yes, this wouldn't work for the most serious cases of depression. It might
help for those who are at a stage where they're willing to try something.

------
zitterbewegung
I’m not sure why none of the studies touch on seasonal variation. I think I
will research more of that but does anyone has a reference?

~~~
TheCowboy
This?
[https://en.wikipedia.org/wiki/Seasonal_affective_disorder](https://en.wikipedia.org/wiki/Seasonal_affective_disorder)

------
akeck
No mention of sleep?

* [http://www.thelancet.com/journals/lanpsy/article/PIIS2215-03...](http://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366\(17\)30328-0/fulltext)

~~~
0xcde4c3db
I think there's a lot of agreement that sleep is important, but not much
consensus around models that are useful for treating it. Right now there's a
big push for CBT-I, but the evidence is mostly low-quality and not really
focused on anything except reducing subjective insomnia severity (this study
is better than most in that respect).

------
ainar-g
A book review[1] linked in the article is also very interesting.

[1] [http://slatestarcodex.com/2017/09/05/book-review-surfing-
unc...](http://slatestarcodex.com/2017/09/05/book-review-surfing-uncertainty/)

------
itschekkers
Chekroud (2015) here - just wanted to say that I think SSC is awesome, and
does a terrific job discussing complex problems in psychiatry & philosophy.

~~~
ainar-g
Could you give any recommendations of great articles on that blog? Or should
people just go to the About/Top Posts[1] page and go down the rabbit hole from
there?

[1] [http://slatestarcodex.com/about/](http://slatestarcodex.com/about/)

~~~
berberous
Here’s a reddit survey of people’s favorite posts, which closely matches my
own:

[https://www.reddit.com/r/slatestarcodex/comments/61qrm2/favo...](https://www.reddit.com/r/slatestarcodex/comments/61qrm2/favorite_post_on_ssc_survey_2017_results/)

If your main interest is psychology, though, note that many of the top posts
are more in the sociology and politics realm.

