
Depression is an inflammatory disease; where does inflammation come from? [pdf] - gwern
http://www.researchgate.net/publication/256548327_So_depression_is_an_inflammatory_disease_but_where_does_the_inflammation_come_from/file/72e7e52375de6dedea.pdf
======
pvnick

      Omega-3 fatty acids, which are important components of
      many healthy foods, such as seafood, nuts, legumes and
      leafy green vegetables, act to reduce inflammation
    

Score another point for fish oil supplementation, on top of the already
enormous pile of scientific research showing it to be a miracle chemical (and
I definitely don't say that lightly) [2]. Seriously, if you aren't getting
enough omega 3 fatty acids, either from regularly eating lots of fatty fish or
through supplementation, you're seriously missing out on some good stuff.
Among supplement enthusiasts, it's consistently declared to be one of the only
supplements that's actually useful. I prefer the liquid form [1].

[1] [http://www.amazon.com/Now-Foods-Omega-Lemon-
Flavor/dp/B001B4...](http://www.amazon.com/Now-Foods-Omega-Lemon-
Flavor/dp/B001B4NFNS)

[2]
[http://examine.com/supplements/Fish+Oil/](http://examine.com/supplements/Fish+Oil/)

Edit: added [2], a well-written examine.com page summarizing fish oil effects

~~~
lectrick
Instead of killing fish, here is my favorite nut mix (BY FAR!), which also
happens to be chock full of Omega-3:

[http://smile.amazon.com/Planters-Nutrition-Omega-3-Ounce-
Can...](http://smile.amazon.com/Planters-Nutrition-Omega-3-Ounce-
Canister/dp/B003VMZZ04/ref=sr_1_1)

Cannot recommend enough. A handful for a snack is filling, healthy and not too
caloric.

~~~
Mz
FYI: _Ingredients Walnuts, Sweetened Dried Cranberries (Cranberries, Sugar,
Sunflower Oil), Candy Coated Dark Chocolate Soynuts (Dark Chocolate {Sugar,
Chocolate, Cocoa Butter}, Sugar, Oil Roasted Soybeans {Soybeans, Soybean Oil},
Artificial Color {Includes Caramel Color}, Corn Syrup, Gum Arabic,
Confectioner 's Glaze {Carnauba Wax, Beeswax})._

Without doing serious research on every ingredient listed above, let me
suggest that you (or other interested readers) can just buy Walnuts for the
same effect, without being exposed to all this other crap, which may be a
problem for some people. Walnuts are unusually high in omega 3. I have a lot
of dietary issues and I would be unlikely to eat the above (and I usually do
not eat Planter's because most of their nut mixes are made with peanut oil,
which is highly inflammatory and tends to make me psychotic and suicidal).

I cannot take fish oil. I am allergic to shellfish and I break out in hives
when I take enough fish oil. So I have long eaten walnuts when I want to bump
up my Omega 3 intake. But, for my purposes, a) avoiding problem oils does more
for me than trying to specifically counteract them by adding other oils and b)
eating less acidly also goes a long way to control my inflammatory condition.

~~~
astrange
Walnuts have more omega-6 than omega-3, so you're probably not getting any of
the effect from it. The two cancel each other out.

~~~
denzil_correa
[http://www.hsph.harvard.edu/nutritionsource/omega-3/](http://www.hsph.harvard.edu/nutritionsource/omega-3/)

Frank Sacks (Prof. of Cardiovascular Disease Prevention, Dept. of Nutrition)

> There are two major types of omega-3 fatty acids in our diets: One type is
> alpha-linolenic acid (ALA), which is found in some vegetable oils, such as
> soybean, rapeseed (canola), and flaxseed, and in walnuts. ALA is also found
> in some green vegetables, such as Brussels sprouts, kale, spinach, and salad
> greens. The other type, eicosapentaenoic acid (EPA) and docosahexaenoic acid
> (DHA), is found in fatty fish. The body partially converts ALA to EPA and
> DHA.

------
tokenadult
It took me a while to slog through that whole long list of references at the
end of the end of the article, but correlational study designs don't impress
more by being numerous, especially when most of them are published in
middling-to-lousy journals. That's what isn't fun about reading about medical
issues here on Hacker News: too many of the articles kindly submitted here are
of much too low quality to be worthy of our attention. There are some
intriguing ideas in this opinion piece, but basically hardly anything there is
backed up by experimental studies, not in a human study and not even in an
animal study. The title of the article reflects an attempt to come up with a
One True Cause of depression that surely is not the one true cause (most
doctors who are experts in depression, or in inflammation, do NOT characterize
depression as an "inflammatory disease") and then the article goes off the
rails from there.

Check back when there is better established evidence about treatment. A better
read about depression by a more informed physician would be a book review
submitted recently to HN[1] that was hardly noticed when it was submitted.

[1] [http://www.sciencebasedmedicine.org/depression-re-
examined-a...](http://www.sciencebasedmedicine.org/depression-re-examined-a-
new-way-to-look-at-an-old-puzzle/)

------
Harj
You can check your inflammation levels via a blood test called hs-CRP
([http://en.wikipedia.org/wiki/C-reactive_protein](http://en.wikipedia.org/wiki/C-reactive_protein)).

I took it and was surprised to learn I was in the high risk range. I tried a
vegetarian diet for just under a month, re-tested and I'd dropped into the low
risk range (this was the only lifestyle change I made that month). I found
that a full vegetarian diet isn't sustainable for me so now I'm trying out
only having meat once a day (usually for dinner) and will re-test to see what
result that has. I suspect that the absence of meat may have been less
important than the increase in vegetables.

The caveat is that hs-CRP isn't a perfect test because your result can be
spiked temporarily if e.g. your body is recovering from intense exercise or a
cold. That's why I think it's a good test to do more regularly and have
longitudinal data for.

I've been spending a bunch of time getting more comprehensive blood tests
recently. If you've any questions feel free to ping me (harjeet [dot] taggar
[at] gmail).

~~~
awolf
For a counter-point, I eat an extremely meat heavy diet and have a superb CRP
number (.23).

It's more likely about avoiding low quality meats, which unfortunately is what
95% of the meat produced in the US is.

~~~
Harj
That's a very good point. Quality of meat isn't something that seems to be
accounted for in studies linking meat consumption to various diseases/health
issues.

Out of curiousity, do you eat a lot of vegetables?

~~~
awolf
Estimating here but I'd put my breakdown by calorie as:

-45% high quality meat (grassfed, pastured, cage-free depending on species)

-10% low quality meat (traditional supermarket stuff)

-30% green leafy vegetables (read: very low non-dietary-fiber carbs)

-10% fruit or carby veggies (e.g. tubers)

-5% grains (never gluten containing)

So I definitely have other confounding factors that might influence my CRP
number: low carbs, very low grains. That said, I arrived at my current diet
via 3.5 years of A/B testing what works for me, optimizing for specifically
what causes my digestion the least inflammation. I'm very happy with the
results.

------
yogi123
Recent articles have tied omega 3 intake to increased risk of prostate cancer.
Got a lot of press last year. I took Omega 3 for the last 14 years. Spent
thousands buying Nordic Naturals from Whole Foods at $25/bottle. Whenever I'd
stop taking it, I felt a decline in mood so thought it had good systemic
benefits. When I went off it this time, I felt zero change before or after
(haven't taken since last summer).

This study was the last straw. I'd already given up supplements and even a
daily multivitamin as studies indicate no positive effect and possible harm.
Now I take no supplements. The more I read the more I'm convinced it's faulty
science and marketing. A healthy, varied diet of mainly plant based foods
should provide all that most people need. If you look at links to omega 3
studies on Wikipedia I don't recall there being conclusive positive evidence,
but maybe I'm wrong. Couple of links on prostate cancer study and whether it's
accurate or not:

[http://www.cancer.org/cancer/news/omega-3-fatty-acids-
linked...](http://www.cancer.org/cancer/news/omega-3-fatty-acids-linked-to-
increase-in-prostate-cancer-risk)

[http://health.heraldtribune.com/2013/08/26/dr-oz-
omega-3-can...](http://health.heraldtribune.com/2013/08/26/dr-oz-
omega-3-cancer-link-pretty-fishy/)

[http://articles.mercola.com/sites/articles/archive/2013/07/3...](http://articles.mercola.com/sites/articles/archive/2013/07/31/omega-3-fats.aspx)

~~~
js2
Still, some vitamins may be worth supplementing depending upon your diet,
exposure to sun, and activity level. For example:

[http://examine.com/supplements/Vitamin+D/](http://examine.com/supplements/Vitamin+D/)

[http://examine.com/supplements/Magnesium/](http://examine.com/supplements/Magnesium/)

[http://examine.com/supplements/Vitamin+K/](http://examine.com/supplements/Vitamin+K/)

~~~
meowface
Is there an effective way to know which vitamins you're missing? Can full
blood tests help tell you which vitamins you should be taking daily?

~~~
marvin
It would be so fantastic if we could just have a chip implanted to
continuously measure this stuff, then download it and analyze on a daily,
weekly, monthly and annual basis. There's so much cool science to be done
here, especially if this is done on a global scale.

------
bunderbunder
You can practically set your watch by the timing of the latest meme that
purports to identify the One True Panacea for Clinical Depression™. Looking
like it'll be time to pull the crown on mine pretty soon.

------
mattgreenrocks
The link between depression and inflammation is news to me. Is it fully
accepted, or still being worked on? I've had bad run-ins with both, sometimes,
at the same time. A particular case was a bad burnout incident I endured a few
years ago. I saw _many_ doctors trying to figure out why my hands and wrists
had enormous amounts of tension. MRIs, x-rays, and conduction tests showed no
issues. I had to leave my job and rest for several months entirely to be able
to use them again.

Because of this, I've always suspected a stronger mind-body link than
traditional Western medicine currently admits to (obvious caveat of n = 1). It
seems that whatever state my mind is in, my body follows soon after. Mental
anxiety begets physical tension. It's like my whole body downclocks itself to
deal with things.

The mind _will_ get it's way, no matter how much you resist.

~~~
dllthomas
I think western medicine is pretty on board with the notion that significant
stress causes (or exacerbates) other issues.

As just one random example:

[http://www.webmd.com/mental-health/effects-of-stress-on-
your...](http://www.webmd.com/mental-health/effects-of-stress-on-your-body)

~~~
mattgreenrocks
Yeah, but no doctors asked about my stress, or emotional health, or anything
that could have started me down the line of investigation. I treated it as an
isolated physical problem, not a symptom of stress/mental issues. The response
was always the same: "we don't know...sorry."

Maybe I should've realized that stress was killing me, but I was severely
depressed. It's not like I could see myself objectively.

~~~
cpncrunch
I think the problem is that many patients prefer the idea that they have a
physical illness, so some doctors don't even consider emotional causes. Also,
doctors simply don't have the time needed to deal with these kinds of issues.

~~~
dhoulb
Yeah, I imagine most good doctors know full well it's emotional/stress, but
avoid telling the patients because it's not what patients like to hear, or
they don't think it'll be helpful.

Pharmaceutical treatments for stress have some harmful side effects, whereas
just sending them away with "don't worry about it" and a lollipop might go a
good way to alleviating some of it.

------
stared
Some premises of this article are at least sound, at least, fishy. Easy
language, lot of promises, and a lot of plausible things but not necessarily
with causal relation.

It starts with "We now know that depression is associated with [...]", where
AFAIK we are far from pinning down etiology of depression (there may be
multiple mechanisms, etc). And it is one of reasons why antidepressant have
relatively low effectiveness. The abstract ends with a longer list of things
that make it flashy.

Moreover, things like smoking are sometimes considered actually having mildly
anti-depressive effect (though it is disputed).

I don't say that the paper is wrong. Just a paper not listing doubts and
promising a lot should be less believed that one making very humble
observations (but the later one would not make HN frontpage, hence the bias).

------
adammil
Can anyone acquainted with the hard sciences comment on whether this paper
passes even a basic sniff test? The title of the paper and so many references
to other psychiatry journals seem like potential red flags.

~~~
stared
I saw some red flags as well (see my comment), so I asked a question:

[http://cogsci.stackexchange.com/questions/5841/is-it-
univers...](http://cogsci.stackexchange.com/questions/5841/is-it-universally-
accepted-that-depression-is-an-inflammatory-disease)

------
abdophoto
Inflammation in the body has been correlated with a lot of diseases believe it
or not. Gluten is one of the big contributors to inflammation in the body. A
lot of people laugh at the whole "Gluten Free" thing, but there's a good bit
of evidence that significantly reducing or removing it from your diet can make
a serious impact.

~~~
josephpmay
Could you point me to the "good bit of evidence" that shows this?

~~~
abdophoto
Less than 2 years ago, my wife was diagnosed with MS (Multiple sclerosis). As
soon as we found out, I started digging like crazy to learn more about why
this happened and what we could do to prevent it from progressing. I'm a big
believer in that the body has the ability to heal itself by avoiding certain
foods and intaking others. I mean, food is fuel we put in our body.

After digging for a while, I came upon some staggering discoveries. First,
there are people who have reversed their MS almost completely on diet alone.
The diets consist of A LOT of high-nutrition fruits and vegetables along with
Omega 3's, organic meats, etc. These Paleo-like diets also forbid gluten with
the main reason being that it causes serious inflammation in some folks. This
TEDx video by Dr. Terry Wahl was very helpful
([http://www.youtube.com/watch?v=KLjgBLwH3Wc](http://www.youtube.com/watch?v=KLjgBLwH3Wc)).
I read her book and it literally laid the foundation for which changed our
eating habits entirely.

A month or so after, we flew out to Massachusetts to a well-known wellness
center where they performed various blood and stool tests. The Dr's (including
a Nutritionist) sat down with us for the entire day and asked about daily
habits from what our work days were like to what we ate. Without mentioning my
own research, they also said that gluten is something we should completely
remove from our diet.

There's a ton of other stuff out there, but since removing gluten entirely, my
wife has felt great. We just did an MRI and she has no new lesions. She no
longer experiences blurriness or weakness which is great. It may not be
completely because of Gluten, but removing seems to have seriously made a
impact.

~~~
gphilip
All of this seems to be anecdotal. Do you know of any research (as in,
studies) which support any of this?

~~~
msandford
I love that anecdotes are considered worthless in medicine when in fact
they're very clearly good places to start.

Take an anecdote and do a small population study to try and find correlation.
Then if there are any significant results, start looking for causation.

In history nothing is legit except for primary sources. In medicine, it seems,
primary sources -- no matter how compelling -- are worth a damn. Hilarious.

~~~
bronson
No. Medicine is so broad and subjective that it's easy to find an anecdote
implying almost anything. That's why expensive double blind is so important --
even doctors fool themselves.

How many "carrots cured my cancer" wild goose chases would it take to bankrupt
even the biggest company? Whatever that number is, it's smaller than the
number of wild-ass medical anecdotes rolling around out there.

Of course, everybody thinks that their own anecdote is compelling and obvious
and all their friends on carb-free diets are idiots...

------
hmhrex
Can't wait to read this. As a person who has dealt with severe depression, and
has come through it alive, I'm always interested in new research on the
subject.

~~~
tannerc
Same. From what I've read so far (only partially through the paper) a lot of
this is what we already know, but with more evidence for the claims. Really
helpful for those of us who continue to combat depression on a regular basis.

~~~
cpncrunch
Actually, I think you might be better looking elsewhere for help with
depression. In my own experience, and that of other people I know,
psychological factors have always been the main cause of depression, and
resolving them results in curing the depression. The problem is that it isn't
always easy to identify the factors causing the depression.

As for the science: we do know that both psychological stressors and
infections both cause inflammation. Stress results in activation of the HPA
axis and sympathetic nervous system, which screws up the immune system in
various ways (including inflammation). Conversely, having a severe infection
can make you feel depressed.

It's really just a theory that inflammation causes depression. I think it's
more likely that it's a result of cortisol and/or neurotransmitters (i.e. too
much brain activity). Cortisol seems a more likely candidate for being central
to depression in my opinion.

The science here seems to be based on a desire to have a physical rather than
a psychological cause for depression. Michael Maes has a history of that (see
his CFS publications).

~~~
dhoulb
Seems like taking action in the real world and avoiding sources of
inflammation would have a positive psychological effect. Giving the person a
feeling of control over one area of their life.

Surely that would be beneficial, whether or not the link between depression
and inflammation is scientifically proven?

~~~
cpncrunch
Sure, anything can be a placebo effect. However I myself prefer to understand
exactly what is happening rather than believing fairy stories, and I think
it's fairer to patients as well.

Unfortunately there is a lot of dubious science out there, and a lot of
patients who prefer the fairy stories.

Having said that, doing things like exercising and having a good diet will
certainly improve health. Exercise has proven to be very beneficial for
depression, although I don't think that inflammation has been proven to be
what mediates the effect.

------
courtf
Pretty fascinating, I didn't realize there were any links between depression
and inflammation. In addition to suffering from depression starting at a
fairly young age, I also have allergic reactions that result in inflammatory
responses to seemingly random environmental factors. This is something that
appears to run in the family. I wonder if addressing the allergic symptom
would suppress some of the depressive ones?

~~~
manmal
I've suffered quite a lot from inflammatory responses to food (especially
gluten and casein) and had mental symptoms similar to depression (not clinical
though). Water retention, pain, weakness, the whole lot. It took some years
until I made the connection and have since stayed on a gluten- and casein-free
diet, adding fish oil and apple cider vinegar. I lost > 30 pounds since
(inflammation seems to cancel out weight loss) and feel great mentally (most
of the time). Whenever I have a setback, I become irritable and depressive -
usually quickly revertable by two fish oil capsules and a glass of diluted ACV
(moodiness disappears within 2 hours; water retention takes 1-2 days to
disappear again - this seems to be associated with the lymphatic system).

------
jaggederest
I suspect there may be some posts here dismissing a lot of this as obvious -
but it's actually really interesting to hear further evidence that a lot of
lifestyle factors really do play a large role as we thought.

The best part about things like this is that, as they say, they're amenable to
change - you can affect them, so you can reduce the severity of the feedback
loop that makes depression so insidious.

~~~
dfc
If a lot of depression's hows/whats/whys were "obvious" this article would not
be included in the journal's "Current Controversies in Psychiatry."[^1]

[^1]:
[https://www.biomedcentral.com/bmcmed/series/CCP](https://www.biomedcentral.com/bmcmed/series/CCP)

------
kingkawn
Why is there an assumption that the inflammation comes from anything other
than the mind state of depression itself?

~~~
jonsen
[http://www.sciencebasedmedicine.org/depression-re-
examined-a...](http://www.sciencebasedmedicine.org/depression-re-examined-a-
new-way-to-look-at-an-old-puzzle/)

~~~
cpncrunch
That study is interesting, but doesn't mention inflammation. It basically says
that depression is a result of stress.

~~~
jonsen
Exactly. Then _maybe_ the order is stress -> depression -> inflammation.

~~~
cpncrunch
I think that is likely. Or perhaps depression and inflammation are both a
result of stress (through HPA axis and SNS activation).

~~~
kingkawn
I guess my original point is that they're trying to look for the mechanism of
the inflammation because they assume that by solving the inflammation that the
depression will be solved, whereas it could be that the inflammation is a
protective reaction against depression the same way that it is a in large part
a protective reaction against other forms of illness.

------
ivan_ah
direct link:
[http://www.biomedcentral.com/1741-7015/11/200](http://www.biomedcentral.com/1741-7015/11/200)

------
lectrick
This is actually a fascinating paper. Keep reading until you see the
connection between inflammation, exercise and depression... Wow!

------
josh-wrale
I have a conjecture about depression. I believe that autoimmune conditions
(e.g. hypothyroidism, MS, vitamin D deficiency) are sometimes a result of the
self-hate associated with severe bouts of depression. The individual feels
adversely about their existence, and so the body sets about deconstructing
itself. I would be very happy to learn this is never the case, but I suspect
that it sometimes is the case. (see:
[https://en.wikipedia.org/wiki/Nocebo](https://en.wikipedia.org/wiki/Nocebo) )

------
jmnicolas
I suffer from depression for more than 20 years. Here is what should be done
to fight it effectively :

\- take anti-depressants \- wake up every day early and at the same time (6 AM
from Monday to Sunday) \- when there is not enough sun outside, sit 30 minutes
in front of a full specter lamp \- eat healthy (vegetables & fish oil) \- have
some physical activity (walking, standing desk) \- socialize

If I was able to effectively do the last 3 things I think depression would
have no impact in my life.

------
lutusp
I'll bet this new empirical scientific result will make psychiatrists and
psychologists abandon talk therapy and their questionable anti-depression
drugs, right away, in the public interest. Let's all hold our breath for that
outcome.

[http://www.planet-
science.com/media/24009/holding%20breath_9...](http://www.planet-
science.com/media/24009/holding%20breath_91390615_316x295.jpg)

------
derefr
I'm curious: does this imply that plain-old non-specific anti-inflammatory
drugs combat depression? I'm aware that sleep-deprivation, cold-caps, and,
oddly-enough, ketamine all have anti-depressant effects, and that these are
mostly unexplained—would the link here be that these things have anti-
inflammatory effects on the brain?

~~~
Lerc
I suffer from depression and a grab bag of auto-immune/inflammatory
conditions.

The drug that seems to have the biggest impact upon my depression is
Etanercept despite it being primarily to treat my arthritis etc,

Ketamine would be cheaper. hell, heroin would be cheaper.

~~~
pantalaimon
Ketamine is actually quite effective

[http://ajp.psychiatryonline.org/article.aspx?articleid=17333...](http://ajp.psychiatryonline.org/article.aspx?articleid=1733363)

------
benched
Look I'll just say it. This strongly matches the pattern of all the other
hiding-in-plain-sight, simplistic explanations for complex bio-existential
problems, that turn out to be bullshit.

~~~
marcosdumay
Yet, nearly all breakthroughs in medicine seem to follow that same pattern, at
least for me, an outsider.

I can't throw it away that easily, and by the way you phrase your comment, I
think you can't either. Yes, the fact that it is in the oppinion column isn't
a good indicator... I'm in the "waitting further results" mode.

~~~
illuminate
"Yet, nearly all breakthroughs in medicine seem to follow that same pattern,
at least for me, an outsider."

Yes, the pattern of selection bias.

