new theories regarding depression
January 9, 2015 5:46 PM   Subscribe

"We know that people may be genetically pre-disposed to depression and anxiety disorders. We also know that specific life events may trigger depressive episodes in those who have previously been the picture of mental health. But so far we've been unable to identify one single, definitive catalyst. However, new research suggests that, for some people, depression may be caused by something as simple as an allergic reaction – a reaction to inflammation; a product of the body, not the mind."
So, scientists are asking: If ill people feel and act a lot like depressed people, might there be a link? Yes, basically. It's all about inflammation – that clever red siren we have in our immune system that lets the body know something is wrong and it needs to be fixed. Proteins called cytokines cause inflammation and flick the brain's "sickness" switch – i.e. make us sad and still. Cytokines skyrocket during depressive episodes and, in those with bipolar disorder, halt in remission. The fact that "normal", healthy people can become temporarily anxious or depressed after receiving an inflammatory vaccine – like typhoid – lends further credence to the theory.
Guardian - Is depression a kind of allergic reaction?

NYTimes - What If We're Wrong About Depression?

Discover - Depression's Dance With Inflammation
“If you block inflammation in people who don’t have high levels of inflammation, you can do them a disservice,” Miller says. “What’s now becoming better appreciated is that there is a certain level of inflammatory cytokines that is probably necessary for brain function.” The study, published in 2013, shows that the role of inflammation in mental health might be more nuanced than once thought.

*Study: Common Painkillers Reduce The Effectiveness Of SSRI Antidepressants
*Magic Mushrooms Expand The Mind By Dampening Brain Activity; May Help Depression

Pacific Standard - Hallucinogens, Starvation, and Magnets: A New Cure for Depression?
posted by flex (77 comments total) 125 users marked this as a favorite
 
Silly western mind-body duality: the mind has always been part of the body.
posted by I-Write-Essays at 5:52 PM on January 9, 2015 [39 favorites]


Hallucinogens, Starvation, and Magnets: A New Cure for Depression?

If you want a vision of the future, imagine a hungry dude, tripping balls, wearing horseshoe-magnet earmuffs — forever.
posted by compartment at 5:56 PM on January 9, 2015 [27 favorites]


There are probably lots of different things we call "depression", each with their own cause. When I get depressed I'm usually thinking poorly, so traditional cognitive therapy works pretty well for me. I've heard from people that cognitive therapy does absolutely nothing for them. So this is probably the tip of the iceberg as far as understanding what depression is.
posted by gehenna_lion at 6:08 PM on January 9, 2015 [10 favorites]


in the NYT piece linked above:
A significant body of research, he said, supports “inflammation as being sort of a common denominator, and then there are a number of ways to get there. And I think infectious agents are one path of many roads to Rome.”

His team has experimented with treating depressed patients with an anti-inflammatory drug, and found that those with high levels of a particular blood marker for inflammation improved significantly. “This for us in psychiatry is a first,” he said, “where you can actually measure something in the blood.” Such an approach “gets into personalized medicine in a way that is very exciting for us in psychiatry.”

However, he cautioned, “nobody’s figured out what’s the best anti-inflammatory.” And most researchers “are still at the point of the proof of concept, making sure that if you do in fact block inflammation that that would reduce these behavioral changes.”

Dr. Miller also noted that only about 20 to 30 percent of depressed patients show high levels of inflammation. These patients are also less likely than others to respond well to current forms of treatment for depression.

Indeed, what many researchers seem to agree on is that depression may not be one illness at all. It’s “probably the case that it’s not a single disorder,” said Dr. Hollon. “It’s probably the fever of modern psychiatry — a lot of different things can cause it.”


And while they’ve made progress, researchers are still trying to find out what all those things are.
posted by flex at 6:14 PM on January 9, 2015 [31 favorites]


Just cracked my phone screen, I favorited this so hard.

Great FPP.
Thank you.
Thank you.
posted by armoir from antproof case at 6:34 PM on January 9, 2015 [1 favorite]


I've heard about the inflammation hypothesis from several credible sources now. Also, anecdotally, my own major depression improved significantly after starting on strong NSAIDs for my chronic crippling arthritis (although I'm not sure how you distinguish the effects of the anti-inflammatories from simply having fewer rational reasons to be depressed due to no longer being in as much pain or as disabled as before).
posted by Jacqueline at 6:39 PM on January 9, 2015 [7 favorites]


This post is well put together. Thanks for making it.
posted by Tell Me No Lies at 6:42 PM on January 9, 2015


tldr will it fix me?
posted by mrgroweler at 6:49 PM on January 9, 2015 [16 favorites]


Indeed, what many researchers seem to agree on is that depression may not be one illness at all. It’s “probably the case that it’s not a single disorder,” said Dr. Hollon. “It’s probably the fever of modern psychiatry — a lot of different things can cause it.”

a friend of mine was musing about this over the holidays -- middle aged like myself.

"It's like everybody I know is depressed these days," he said. "But then I dig a little deeper and person A is dealing with both her parents dying in the last year, person B blew his back out and has to change careers, person C just had her youngest kid go off to college. And so on. These people aren't depressed. They're unhappy for reasons. Depression is person D who's just plain unhappy for no particular reason. Isn't it?"

I just shrugged and realized I had no idea.
posted by philip-random at 6:50 PM on January 9, 2015 [16 favorites]


I dunno. The first Vice article is pretty poorly done.

Lets break it down:
1. Random Brain MRI picture to lend credence.
2. The Lede: Maybe Depression is an allerigic reaction?
3. Quote one psychologist's opinion.
4. Argument: We all feel like crap when we're sick... so maybe we're sick when we feel like crap.
5. Personal anecdote about depression that doesn't add much.
6. "We could be 5 years from knowing a blood test about inflammation": Many bio-markers of inflammation are easily and readily available. All of the "inflammatory" markers are pre-existing lab tests. Science fiction about then, we can just cure it.
7. Random tangent about mental health stigma and anorexia in boys.
8. Mention more buzzwords like "cytokines" and "inflammation."

In essence, there are a handful of psychologists who feel like, maybe, inflammation causes depression. It's a theory and little else. There's very little concrete here to hang your hat on, and it doesn't mention any of the other competing hypotheses of the etiology of depression. The word Serotonin isn't even mentioned once....
posted by cacofonie at 7:21 PM on January 9, 2015 [16 favorites]


I did a post that was a lot more about the relationships between trauma, poor health factors, and adversity and increased inflammation as well as increased inflammation and depression.

If you want something more sciency try this one .

Great post flex!
posted by xarnop at 7:26 PM on January 9, 2015 [10 favorites]


tldr will it fix me?

Well, try taking aspirin and megadoses of omega 3 daily and get back to us in 6 months and let us know.
posted by Jacqueline at 7:29 PM on January 9, 2015


Listening to a Robert Sapolsky lecture cheers me up.
posted by ovvl at 7:32 PM on January 9, 2015 [5 favorites]


It probably doesn't waste time trying to discuss the seratonin theories because the theory is not substantiated by evidence:

"Contemporary neuroscience research has failed to confirm any serotonergic lesion in any mental disorder, and has in fact provided significant counterevidence to the explanation of a simple neurotransmitter deficiency. Modern neuroscience has instead shown that the brain is vastly complex and poorly understood [11]. While neuroscience is a rapidly advancing field, to propose that researchers can objectively identify a “chemical imbalance” at the molecular level is not compatible with the extant science."
posted by xarnop at 7:33 PM on January 9, 2015 [7 favorites]


FOR SOME PEOPLE.

That is the part most people won't read. FOR SOME PEOPLE.
posted by maryr at 7:36 PM on January 9, 2015 [14 favorites]


I'm with you, cacophonie - but at the same time, I'm a big believer in the idea that depression and many other disorders are essentially (if not totally) physical in nature.
posted by BlackLeotardFront at 7:38 PM on January 9, 2015


All disorders are totally physical in nature!
posted by Justinian at 7:42 PM on January 9, 2015 [21 favorites]


tldr will it fix me?

Well, try taking aspirin and megadoses of omega 3 daily and get back to us in 6 months and let us know.


Or, you know, talk to a therapist about it. And better yet, do both.
posted by maryr at 7:50 PM on January 9, 2015 [1 favorite]


I was pretty struck by the reference to turmeric; I've struggled with depression for a long time, and when I get really down, I like to eat Indian food to feel better. Now granted, that might just be because it is creamy and spicy and delicious and who wouldn't feel better after eating it, but I could've also been unconsciously self-medicating. Sometimes our stomachs know what we need before our brains do.

Also interesting: the reference to omega-3 fatty acids. There's this book called The Depression Cure. The bulk of the titular cure is just eating right, getting sunlight and exercise. But if you're (understandably) too depressed to eat right, the author recommends starting by taking a bunch of fish oil pills everyday, along with some vitamins. Fish oil, of course, is really high in omega-3s. I don't recall him talking about inflammation as a possible cause of depression; he mostly focused on how studies showed that doses of omega-3 helped depressed people feel better.
posted by Anyamatopoeia at 7:55 PM on January 9, 2015 [2 favorites]


It also adds to my theory that nurturing, feeding, and caring for the mourning, traumatized, and sick through helping them with household care and fresh healthy food preparation is a big part of helping people heal from adversity. We are trying to skip this step by throwing pills at people who need to mourn or heal over a long period of time, meaning they don't need to be pressured to function at peak performance 24/7 the way our culture pushes everyone- I'm not opposed to pills being accessible for people who ALREADY HAVE access to care, prepared meals and assistance keeping up with life, processing feeling and being heard etc... but many of these solutions need to become higher priorities as our understanding of health points to them as important components of health and well being.
posted by xarnop at 7:59 PM on January 9, 2015 [28 favorites]


I really hate it when my sense of fuck, I'm depressed get inflamed.
posted by Catblack at 8:05 PM on January 9, 2015 [1 favorite]


Curiously there are drugs prescribed for central nerve pain that help depression, and drugs for depression that help central nerve pain. They are almost the same thing, for certain drugs.

One thing is 'body burden', the cocktail of heavy metals and chemicals from the environment that build up in the body. Given our chemical/nuclear/biological brave new world, it's possible inflammation is a common response that manifests as depression on the low end and more serious diseases on the higher end (MS, heart disease etc).
posted by stbalbach at 8:14 PM on January 9, 2015 [2 favorites]


I have tried a bunch of anti-depressants, and literally the best thing I have found (by accident) is DayQuil + coffee. Totally anecdotal evidence, but there it is.
posted by desjardins at 8:18 PM on January 9, 2015 [5 favorites]


Sometimes our stomachs know what we need before our brains do.

I was surprised to learn that more of the nervous system is in the GI tract than anywhere else. It definitely put a lot of my training on its head, so to speak.
posted by a lungful of dragon at 8:23 PM on January 9, 2015 [5 favorites]


There are inflammatory and anti-inflammatory foods which some people use to improve their mood :
"Suggested diets to reduce inflammation include those rich in vegetables and low in simple carbohydrates and fats, such as saturated fats and trans fats.

[An anti-inflammatory diet avoids refined oils and sugars, and show a preference for so-called anti-inflammatory foods.] Anti-inflammatory foods include most colorful fruits and vegetables, oily fish, nuts, seeds, and certain spices, such as ginger, garlic and cayenne. Extra-virgin olive oil contains the chemical oleocanthal that acts similarly to ibuprofen."
Eat more fruits and vegetables. Eat less meat, grains, pre-packaged food, etc.
posted by jeffburdges at 8:53 PM on January 9, 2015 [3 favorites]


i thought inflammation was like toxins, in that it's just generic and scary enough to be a modern bogeyman?

anyway, when i see something like this i vaguely entertain big notions of going to science school and devoting my life to helping along this kind of research.

but here on planet reality, count me in the group that is too depressed to do much more than raise an eyelid, grunt, and leak some saliva in the general direction of this post. (that means thank you.)

/particularlybadweek
posted by ghostbikes at 9:16 PM on January 9, 2015 [7 favorites]


i thought inflammation was like toxins

But cytokines and other inflammation markers are measurable in the blood. "Toxins" are not measurable unless you're one of the colonic people in which case it can be measured, but it's just poop.
posted by Lyn Never at 9:19 PM on January 9, 2015 [1 favorite]


ah. thumbs_up_emoji.jpg
posted by ghostbikes at 9:21 PM on January 9, 2015


Indeed, strbachban. Gabapentin/Neurontin is prescribed for both neuropathy and depression. It's almost like the mind is made of neurons...
posted by effugas at 9:34 PM on January 9, 2015 [5 favorites]


Andrew Weil has been trying to point to the link between inflammation and depression for a long time.
posted by Blitz at 9:50 PM on January 9, 2015 [1 favorite]


Interestingly enough, it also looks like the rather popular antidepressant Wellbutrin has been shown to have anti-inflammatory activity through its effects on TNF and IFN. From the literature, it's been tried out in Crohn's disease, psoriasis and atopic dermatitis, among other conditions. I think I even saw a paper suggesting that it be used to treat leukemia. Weird!
posted by un petit cadeau at 9:56 PM on January 9, 2015 [2 favorites]


What is "inflammation"? I've noticed I feel significantly less depressed when on allergy medications and/or omeprazole (Prilosec) for allergies and acid reflux, respectively. I just assumed there was something speed-like in the formulation that was making me feel good. Prilosec especially.
posted by stoneandstar at 10:06 PM on January 9, 2015 [1 favorite]


We are at a point in medical science where I cannot distinguish the woo from the real science without an hour of research (at best, I'm still unsure about some of the claims in this post)- and I am a moderately well educated smart person. I cannot imagine how terrifyingly difficult it is for someone who doesn't LIKE reading research papers to make sense of what is and isn't really going to help them.
posted by FritoKAL at 10:06 PM on January 9, 2015 [31 favorites]


To clarify, my real question is just, can cytokines result from allergies and/or rather bad acid reflux? I know they both make me feel like shit...
posted by stoneandstar at 10:07 PM on January 9, 2015


Lyn Never: But cytokines and other inflammation markers are measurable in the blood. "Toxins" are not measurable unless you're one of the colonic people in which case it can be measured, but it's just poop.

I think the potential cultural analogy between "inflammation" and "toxins" is a lot closer than that actually. 'Toxins' are a physical thing (several different things) and can be measured; just today I saw this article in Science on how cells "detoxify" themselves of a byproduct, superoxide anions, by converting it to hydrogen peroxide then water. Of course there's not much a fad detox diet is going to do to help your cells with superoxide. It probably won't help with ricin or cadmium, either, two other real measurable things that can legitimately be called toxins.

Both inflammation and toxins have that real-but-nebulous status that makes them so attractive to the woo crowd.
posted by traveler_ at 10:07 PM on January 9, 2015 [5 favorites]


I did a post that was a lot more about the relationships between trauma, poor health factors, and adversity and increased inflammation as well as increased inflammation and depression.

Yes, I really appreciated this.

I take fairly large doses of fish oil, and have been for years, as well as many other powerful anti-inflammatories such as turmeric and ginger capsules, and eat an extremely healthy diet. I am depressed, but I know as depressed as I often am, I know I should be much more depressed. Then I wonder about the often grueling and (seeming) futility of my constant efforts to "be healthy", and I truly think it's likely that it is, and has been helping me for years. I will always be convinced of the relationship between different aspects of wellness.
posted by Blitz at 10:09 PM on January 9, 2015 [1 favorite]


I know 2 people who claim to have had significant improvements in mood and energy while taking antibiotics (I forgot which ones). Of course, antibiotics have nasty side-effects if taken all the time. Anti-inflammatory drugs may give a good clue to a new kind of treatment. YMMV, but I would not be surprised if inflammation turns out to be a major contributor for a lot of people who are depressed.
posted by Vibrissae at 10:32 PM on January 9, 2015


@un petit cadeau

One additional note: If I'm not mistaken, serotonin is at least partially responsible for repair of connective tissue, gut lining, and other kinds of tissue. So someone who is depressed due to a low level of available serotonin might be expected to be more inflamed i ways that cause gut troubles, joint problems, etc.
posted by Vibrissae at 10:35 PM on January 9, 2015 [3 favorites]


Indeed, strbachban. Gabapentin/Neurontin is prescribed for both neuropathy and depression.

... and in at least one case that I'm aware of, Gabapentin made somebody's neuropathy magnitudes weirder, with no actual pain relief. In the end, I had to shake my head at the recklessness of a system that would embrace such a dubious "solution".

We are at a point in medical science where I cannot distinguish the woo from the real science without an hour of research (at best, I'm still unsure about some of the claims in this post)-

way too true.
posted by philip-random at 10:49 PM on January 9, 2015


Article: J Random Psychiatrist
says that we're between five and ten years away from a blood test that can measure levels of inflammation in depressed people
We've been 5-10 years away from useful depression biomarkers since the 1960s.

This article under-reports what's actually hospital standard of care for people who are ill. I've on occasion measured cytokines or other inflammatory markers for psychiatric patients, though mainly for unusual psychoses and only rarely for mood disorders. Sometimes they pan out. Most often they do not. The ones that show definite evidence of derangement, and we can treat, great. There's nothing like bleeding someone or extracting teratomic ovaries to rapidly reverse psychosis. Or getting people with liver injury to poop out their inflammatory toxins and bounce back from utterly deranged or suicidal encephalopathy.
posted by meehawl at 11:17 PM on January 9, 2015 [9 favorites]


Well, I'm all for the scientists finding alternate theories and ways to treat depression. Because the current favorite method of (a) talk to psychiatrist for 5 minutes, (b) be immediately prescribed an SSRI that will be guaranteed to give you side effects that may or may not go away later or ever, (c) but meanwhile you have to put up with them for at least six weeks to see if it works at all or well, and (d) they might inexplicably poop out and then you start that shit all over again, just sounds totally crazy to me, and kind of the equivalent of using leeches or something.

People give me crap for not wanting to hop aboard the drug roller coaster, which I don't want to for various reasons such as gagging on pills (yes, I tried that thread with the gagging remedies, still didn't work!) and generally being leery of taking most medication and being terrible about taking anything consistently, but really, the current process sounds like an utter crap shoot and is as at least 50/50 as to whether or not anyone gets worse or better. Seriously, this is all we've got now?! That's my only option, really? Sorry, but I can't be fucked up with, say, an excruciating permaheadache that won't go away due to my new SSRI at work for six weeks, I'd get fired. However bad I feel, it never seems THAT bad enough to be worth the shitty roller coaster of drug trials.

Fuck, no. Which is why stuff like this (inflammation theory, research into 'shrooms, what have you) cheers me. Maybe someday, sometime there will be a less goddamned shitty crapshooty option to try. Hell, maybe someday they can actually do tests to figure out what WOULD work on you before you start trial after trial. That might be nice.

Meanwhile, I've had an asstastic week, but after going to a session of hippie-dippie EFT/tapping tonight, I am actually in a good mood and did not go home to drink after a draining day of work like I normally would have. Well, SOMETHING worked! Huzzah!
posted by jenfullmoon at 11:25 PM on January 9, 2015 [7 favorites]


xarnop: It probably doesn't waste time trying to discuss the seratonin theories because the theory is not substantiated by evidence:

I don't think the case is closed enough to describe it that way, though. I skimmed through what Google Scholar has as citing that paper, and most of it was people accepting their claims and passing them around uncritically. There was this response by someone with enough conflicts of interest he might as well be considered the "industry perspective" but at least it addresses the science.

What makes me nervous, though—and I admit this is more of a smell test than a hard critique—is that those two authors have been working together for some time on book chapters, opinion articles, that blog I linked, and so on and so forth from a perspective I'll charitably call "bioskeptical". In short, I don't trust them. I'm upset by the language they use in their letter titled Questionable Advertising of Psychotropic Medications and Disease Mongering, and I'm suspicious about Jonathan Leo's own CV describing his own work with:
Research has received international media attention in several mediums, ranging from newspaper articles to live television. This includes coverage by United Press International, Wall Street Journal, ABC News, The New Scientist, Men’s Health, Canadian Medical Association Journal, Medscape, WebMD, Forbes, Fortune, Nature The Psychotherapy Networker, Applied Neurology, Tallahassee Democrat, The Chronicle of Higher Education, The Telegraph [Calcutta, India], Hartford Courant, and DTC Insight. It has also been cited in congressional reports. In addition, FOX-13-Tampa conducted a half-hour live interview about antidepressants.
I've skimmed several of their blog posts and professional publications and they all carry a distinct tone of "big pharma just wants to sell you pills, man". Rhetorically more sophisticated, of course, but not much more scientifically concrete. (I'll go into more detail on that if anyone cares but this is long enough already.)
posted by traveler_ at 11:31 PM on January 9, 2015 [7 favorites]


Andrew Weil has been trying to point to the link between inflammation and depression for a long time.

Maybe he should try not being a giant quack and then people would listen.
posted by Pope Guilty at 11:36 PM on January 9, 2015 [15 favorites]


... and in at least one case that I'm aware of, Gabapentin made somebody's neuropathy magnitudes weirder, with no actual pain relief.

Gabapentin and its close relative Pregabaldin made my chronic pain much worse. With the Gabapentin, I though it was a natural progression of the pain I was in, and only stopping it because of the additional recent development of insomnia caused me to realize that Gabapentin was responsible for the months of addition agony. With Pregabaldin I was on it just long enough for the pain to increase to know it was going to do the same thing.

Not sure what that tells anyone. Other than many of these drugs behave in unexpected ways. I know I was not the only person that Pregabaldin increased pain in; my doctor confessed that she saw someone earlier who said the same thing and assumed the other patient was making it up. I guess two in the same day made her rethink that?
posted by [insert clever name here] at 11:58 PM on January 9, 2015 [2 favorites]


xarnop - you might be interested in the views of Dr Gabor Maté, who's worked with people struggling with addiction. (Nutshell: he agrees with you, lots.) I guess he was looking into therapeutic applications of ayahuasca [terrible audio] until Health Canada shut that down.

The strangest correlation I've come across is anxiety disorders and joint hypermobility. I mean I guess, why not, the body is weird. (I was interested in this because I can get on edge sometimes, and can also do party tricks with my shoulders. Though I don't it so often, anymore, but you know, I still can.)

With regard to the subject at hand, there's also now a glutamate theory of depression.

(Also, I used to chew on Advil like candy and it didn't help me with the sads at all, for an n of 1.)
posted by cotton dress sock at 12:01 AM on January 10, 2015 [3 favorites]


Thumbs up to Vitamin D, though.
posted by cotton dress sock at 12:02 AM on January 10, 2015 [2 favorites]


I actually do a lot of work with cytokines (immunology, not neuroscience), and I honestly found these articles confusing. For starters, they don't define their terms. "Cytokines" includes a very diverse range of growth factors and intercellular signalling molecules. Even if you were to narrow it to, say, "inflammatory cytokines", you're still talking about a lot of different (and usually pleiotropic) molecules.

Secondly, correlative studies with cytokines are naturally fraught, since they're involved in so many biological processes. An elevated IL-6 or TNFa in the blood could mean any number of things (you're getting a cold, you've been exercising, you're under stress at work, you haven't slept properly, you're overweight, you ate something that wasn't good for you et.c etc. etc.). So if you're going to implicate them in a particular disease, you need more than correlations. In this regard, the NSAID and anti-TNF data are interesting, because it does look like these drugs do impact on the mental state of people taking them. But they present variable and conflicting results. Also, NSAIDs hit so many things it's impossible to make a conclusive statement about what' pathways (inflammatory, neurosignalling, lipid signalling etc.) are most important for the clinical observations. Similarly, the anti-TNF drug, Infliximab, not only inhibits signalling between TNF and its receptor. It actually causes apoptosis (death) of certain immune cells. So if those cells are indirectly responsible, Infliximab could be mediating it's effects entirely independently of inflammation.

So for me the take home message seems to be we have no idea what's going on in these patients.

Also, am I the only one who immediately thought of that episode in The Knick, where the early 20th century psychiatrist is adamant that infection and inflammation are the cause of melancholy, and promptly removes all of the poor woman's teeth?
posted by kisch mokusch at 12:26 AM on January 10, 2015 [20 favorites]


"It's like everybody I know is depressed these days," he said. "But then I dig a little deeper and person A is dealing with both her parents dying in the last year, person B blew his back out and has to change careers, person C just had her youngest kid go off to college. And so on. These people aren't depressed. They're unhappy for reasons. Depression is person D who's just plain unhappy for no particular reason. Isn't it?"
They could all be clinically depressed; or none of them. Clinical depression is basically diagnosed when it's significantly affecting your ability to function in normal life. It might have specific causes or it might not. High stress and lack of sleep are both common in depression, but are they caused by the depression or causing it? Or both? But depression is a lot more than just unhappiness. Unhappy is an emotional state, that passes, just as all emotions do. Depression sticks around and stops you having emotions properly altogether and screws up your thinking in all sorts of subtle ways.

If you're finding it hard to work (as in jumping off a bridge seems like a fairly viable alternative to going to the office today), it's harming your relationship with friends and family - because you can't cope with having to fake having emotions around them, you're struggling with self-care (eh, I can't face eating, I'll just starve to death on the couch and then I won't have to care any more), then you may be depressed. Plus diagnosis relies on self-reporting of emotional state, so it's kinda a disease that you know when you see it.

It's a bit of a catchall disease - calling it the modern fever is a good one. The end result is the same, to various levels of severity, a mood disorder that results in a significant inability to function.

My personal depression takes the form of a grey mental fog that saps all feelings bar despair and anger. I get stuck in a mental loop of blaming myself for everything, and just spiral down into lack of sleep, and either anger at myself for being so useless and unable to cope with my failures, or just profound inability to care about much at all; I end up wearing a mask that I try to contort into the appropriate expression as everyone keeps having feelings at me I can't respond to - I feel like I'm piloting a broken puppet, someone who has run out of fucks to give. The proximate cause is high stress at work with a bad boss and lack of sleep. Is the level of stress unreasonable? Or am I just broken in being unable to cope with what is normal stress? I honestly don't know.

My SSNI helps me a lot. Cognitive therapy so I can spot early when I'm going on a negative mental blame spiral has helped me. More daylight helps me. More sleep helps me. Exercise doesn't help me much. I do take anti-histamines sometimes for hayfever, and haven't noticed any particular correlation between bad days and good days related to them. My bad days are a lot less worse than they used to be before treatment, and my good days are much, much better. I have feelings now that aren't just pale shadows of real emotions. I feel like I'm living in my own body now, experiencing real things happening to me and around me.

Depression is a complex disease with many causes, and several possible treatments. What works for one person won't work for another. Some treatments work better than others. Do I wish we had a better understanding of it? Of course. One theory of seratonin therapies in depression is that it helps repair damaged neural connectivity, caused by cortisol (commonly called the 'stress hormone'), and that it takes time for that repair work to take place, thus the lag time for SSRI and SNRI, that increase serotonin levels, to take effect.

Brain chemistry is complex, and it's not like we can just start dissecting depressed people to figure out what reactions are going wrong in their particular case. Nor are we even close to fully understanding the complexity arising from those reactions. We can just chuck stuff at the wall that's worked before for some, and see what sticks in any individual case.
posted by ArkhanJG at 2:17 AM on January 10, 2015 [15 favorites]


I read about this in Slate Star Codex: "Chronic Psychitis". The author is a resident psychiatrist, his verdict is "pretty legit".
posted by kandinski at 2:18 AM on January 10, 2015


Sometimes I am allergic to stupid, but then people call me a whiner and give me an extra portion. I puff up, get red in the face and lie down for a while until it passes.
posted by qinn at 2:47 AM on January 10, 2015 [5 favorites]


I'm on board with the concept of "depression" being so complicated and multifaceted that there are many approaches to management. But I do feel that Metafilter is kind of quick to demonize psychiatric medication. The only combination that has worked for me is a careful diet, a ton of exercise, talk therapy and an anti-depressant. I had to work my ass off to find the right psychiatrist and he sure didn't prescribe my medication after a 5 minute appointment.

I think anytime we can move the medical model slightly toward the mind-body connection concept is amazing. But you will pry my lovely, inexpensive, life-saving medication out of my cold dead hands, man.
posted by Pardon Our Dust at 2:55 AM on January 10, 2015 [27 favorites]


Vibrassae: Interesting. Apparently, some antibiotics have psychotropic properties. I found this out when augmentin made me really depressed. It turns out that the clavulanic acid is being tested as an antidepressant.
posted by persona au gratin at 3:24 AM on January 10, 2015


Amen, Pardon Our Dust.
posted by persona au gratin at 3:29 AM on January 10, 2015 [1 favorite]


Andrew Weil has been trying to point to the link between inflammation and depression for a long time

Well that settles it. Where has he published his clinical research on this subject?

As others have said above, brains are part of bodies, and mind is a story we tell ourselves because we don't know enough about brains yet.
posted by spitbull at 5:33 AM on January 10, 2015 [1 favorite]


This is a fantastic article, also from Slate Star Codex, about research on antidepressants.

Basic summary: The "your brain is low on serotonin" theory was never well-supported and probably should not have been marketed so heavily. The supposed new evidence that SSRI drugs are ineffective just misinterprets the meaning of "effective". Still,no one knows why these drugs work. Side effects, especially sexual side effects, had been underreported for various reasons. Bupropion (Wellbutrin) tends not to have the dealbreaker SSRI side effects.
posted by vogon_poet at 6:09 AM on January 10, 2015


Sometimes when I get depressed it's because I'm seeing the world exactly as it is.
posted by dashDashDot at 6:23 AM on January 10, 2015 [13 favorites]


Study: Laughing gas may help in treatment for depression. It seems like there's a "cure" for depression about once a month, based on a tiny sample (20 patients in this case). I'll keep taking my meds and talking with my shrink.
posted by Carol Anne at 6:29 AM on January 10, 2015 [3 favorites]


Depression goes away when I have a modest fever. On the occasion I realized this, I felt quite...level. Unpack that. /derail
posted by datawrangler at 7:39 AM on January 10, 2015 [2 favorites]


Inflammation is the root of many diseases that is not "woowoo" it is basic understood science.
posted by stbalbach at 10:11 AM on January 10, 2015


Where has he published his clinical research on this subject?

My lab has been exploring relationships of transcription factors and disease phenotypes for the last five years or so. Some of the collaborations we have had with other labs have led to interesting results that have not been followed up upon, like relationships between immune system-related TFs responsible for inflammation response and genetic variants associated with schizophrenia. Everyone has papers and grant submissions to get out the door, and there's usually little money to go looking down a rabbit hole. But when these things pop up in boring meetings, it perks up one's attention and reminds us why we keep doing the work.

Now, I'd agree that Weil is a book-peddling quack, and that skepticism is always warranted, and that bioinformatics has and will find all kinds of interesting associations that end up having little clinical significance, but historically we are really only at the very start of exploring this subject, and I wouldn't be surprised to find over the next couple decades that further research finds connections between functional aspects that were heretofore thought distinct.
posted by a lungful of dragon at 10:14 AM on January 10, 2015 [2 favorites]


All disorders are totally physical in nature!

No, not necessarily, not totally, though they always have physical descriptions/analogs, too. The fact that CBT works so well compared to other therapies suggests the disorders are sometimes found at the level of conscious mental processes. Sure, those are physical, too, but they operate at a higher level of abstraction. It's sort of like how software hacks can cause physical problems on a computer. The code is physical, sure, at the lowest level, but the abstracted organizational structures that you find embodied in higher-level code don't necessarily mean anything when viewed only at the level of bits. The meaningful structures are metaphysical--meaning, not about the physical bits, but about their higher order arrangement into more abstract structures. In the same way that abstract code can actually be designed to harm the physical components of a PC despite not being limited to a physical implementation on a particular machine, ideas can potentially reach down causally to damage lower level physical components of the brain.
posted by saulgoodman at 10:23 AM on January 10, 2015 [2 favorites]


That sounds like really cool research, a lungful of dragon.
posted by cotton dress sock at 11:30 AM on January 10, 2015


Just the comments in this thread are fascinating, never mind the links in the posts and comments.

I know that arthritis (rheumatoid and the various HLA-B27 associated types including the one I have, not osteo) is correlated with depression, but I've always been told that had to do with pain and assorted life limitations. Maybe there's a second connection through inflammation issues. I realized recently that my own mood has been significantly lower since I switched off NSAIDs and onto a different treatment. Can't go back, either, as I've now had enough severe allergic reactions to NSAIDs that I'm probably off the entire group permanently.
posted by immlass at 11:44 AM on January 10, 2015 [1 favorite]


But I do feel that Metafilter is kind of quick to demonize psychiatric medication.

for what it's worth, I generally haven't found this. In fact, various MeFi threads over the years have challenged me to take a hard look at my assumptions about depression (in particular, my long held notion that meds are NOT the way to go). I wouldn't say that my mind has changed completely. I would say that I'm far more likely to shut up about what I think and actually listen to what others are saying, because it's clear that this is a deep and complex issue.

What does worry me though are arguments that tend to land hard on the depression-is-a-physiological-affliction-that-we-can-cure-it-if-we-just-find-the-right-combination-of-drugs side of things. Not saying that anyone in this thread is loudly making such claims, but the notion that simple inflammation may be at the root of the despair that makes a long troubled friend want to jump off a bridge -- that just feels way too easy.
posted by philip-random at 1:23 PM on January 10, 2015 [1 favorite]


I don't think anybody's saying "inflammation, case closed!" They're saying that inflammation markers might be relevant to depression. That says nothing about what is causing the inflammation, but it's a clue (and measurable one, which we are in short supply on in mental health), and it's great to have clues about deadly diseases that kill your friends.

I am firmly in the camp that science will one day have the tools necessary to settle mental illness firmly in the biology camp, but that is not to disparage therapy as one of the tools in the toolbox. I think of talk therapy as being like physical/occupational therapy for an injury - it's awesome that I can get my knee replaced, but I'm not going to hop out of bed and go bowling the next day. I've got to strengthen the muscles, I have to learn how to move in ways that help rather than harm my range of motion, how to get in and out of the car without jacking it all up again.

Nobody saying to take away non-medication therapy immediately, but the fact of the matter is that if there's something biological that's disabling the don't-jump mechanism, then no amount of talking will stop it.
posted by Lyn Never at 2:24 PM on January 10, 2015 [4 favorites]


I think most people have agreed by now, in theory, although obviously not in practice, that our mental health (and a lot of other health) experiences are "biopsychosocial", with inter- and intra-personal experience always rooted in physiology, at the same time that it's shaped by the social milieu. Talking is biological - and not in a banal way either, it has biological effects (just like stress and trauma do) - in the same way that all our higher-order processes are physical. I kind of wish the weird dualism that haunts discussion of psychiatric illness (and people, full-stop) would DIAF.
posted by cotton dress sock at 2:49 PM on January 10, 2015 [1 favorite]


Pretty sure my Crohn's disease is a major factor in my depression, so yeah, I get it.
posted by waitingtoderail at 3:53 PM on January 10, 2015 [1 favorite]


"It's like everybody I know is depressed these days," he said. "But then I dig a little deeper and person A is dealing with both her parents dying in the last year, person B blew his back out and has to change careers, person C just had her youngest kid go off to college. And so on. These people aren't depressed. They're unhappy for reasons. Depression is person D who's just plain unhappy for no particular reason. Isn't it?"

Depression can also be persons A, B, or C who have upsetting or stressful things going on which they're having a much harder time dealing with with than they could be because of unbalanced brain chemistry, or unbalanced gut chemistry, or suboptimal cognitive habits, or inflammation, or some other of the who-knows-how-many things that can throw one's brain into depression.

When you think about how complicated brains and minds and bodies are, it seems silly to think there could only be one way of knocking the system out of balance enough to cause clinical depression.

Furthermore, it seems quite likely to me that some people could suffer enough cognitive and/or social stress as to screw up their brain/body chemistry in ways that cross the line from "unhappy for reasons" into clinical depression. (And I hope no one would take it as minimizing the problem of depression to say that that line might actually be a pretty fuzzy one.)
posted by straight at 3:55 PM on January 10, 2015 [2 favorites]


NSAIDS can be hard on the nervous system, and depressing with long term use.
posted by Oyéah at 7:10 PM on January 10, 2015


Some of the collaborations we have had with other labs have led to interesting results that have not been followed up upon, like relationships between immune system-related TFs responsible for inflammation response and genetic variants associated with schizophrenia.

I think there is a longer history and more scientific grounding in the theories associating the immune system to schizophrenia (as opposed to depression). I remember people talking about (some forms of) schizophrenia having an autoimmune component more than 10 years ago. And there were those theories that infection/inflammation during late-stage pregnancy affects neural development in such a way that predisposes the fetus to behavioural abnormalities in later life. It's not my field, though, so I don't know if these theories have fallen out of favour or gained support in recent years.

I do want to qualify my comment above by saying that it is definitely mechanistically feasible for inflammation to play a more direct role in mood and depression (as opposed to being secondary to, well, being sick and depressed about being sick). And god knows with GWAS and some of the other tools at our disposal nowadays it's definitely easier to explore these links than ever before. But people still have to detail exactly what they think is going on so that: a) Clinicians know what they're supposed to be looking for; and b) Researchers can test and modify the theory accordingly as the results come through. It's just so hand-wavy at this point.
posted by kisch mokusch at 7:51 PM on January 10, 2015


But I do feel that Metafilter is kind of quick to demonize psychiatric medication.

It's more that there are a few very strident posters who seem to have a vested interest in dropping into depression threads and saying the same thing no matter how many times they are rebutted. The overall crowd comes down pretty solidly in the "We're not sure why anti-depressants work but they very clearly work" camp.

--

has in fact provided significant counterevidence to the explanation of a simple neurotransmitter deficiency.

I've never heard of a depression theory involving neurotransmitter deficiency. Could you elaborate?
posted by Tell Me No Lies at 4:15 AM on January 11, 2015


I've never heard of a depression theory involving neurotransmitter deficiency. Could you elaborate?

Yes you have, you just didn't know that was what you were hearing. The biggest class of antidepressants -- SSRIs -- is based on this theory.

Serotonin is a neurotransmitter. You take a SSRI (Selective Serotonin Reuptake Inhibitor) to increase the amount of serotonin in your brain by impeding it being reabsorbed.

So, whenever you hear of someone being prescribed SSRIs -- e.g., Prozac, Celexa, Paxil, Zoloft, etc. -- you're hearing of a treatment that adheres to the neurotransmitter deficiency theory.
posted by Jacqueline at 7:19 AM on January 11, 2015 [1 favorite]


*Hands Up*

Yep, my depression appears to have been caused by allergies (multiple, but one food allergy was the lynchpin). I'm still a bit ADHD, but it kind of feels like I'm starting my life from scratch. Well, not scratch, but my 30s are shaping up to be Best Decade EVARR.

I now get/need 1-3 hours less sleep per day, and am more functional. That's a huge chunk of leisure that I NEVER HAD.

If this helps the chunk of people who have the same cause of depression have happier, more productive lives, that's incredibly awesome.

It's not the only cause of depression, obviously, remove any external stressors you can, but most people can think yourself into being scared and stressed without any external factors, and that's where therapy came in.
When I WAS depressed and going along to a depression support group, I still had the stereotypical 'not depressed persons' frustration at the way some of the people in the group would beat themselves up, actively badtalk themselves - I didn't feel like I had the luxury of beating myself up like that, I was already down and hurting and would have spun even deeper very quickly. Kind of like they'd had enough physical health/resilience that they'd built up this habit of beating themselves up, before the negative effects of this really kicked in.
posted by Elysum at 7:21 AM on January 11, 2015


I'd also like to point out that "depression" is a generic term on its own. There's Major Depression (aka major depressive disorder) and Dysthymia, which they've found to be different animals. So saying depression is a catchall is I think spot on and researchers, and journalists, really need to define what they're researching exactly (which I've found to mostly be Major Depression).

(yes the treatment and outcomes can be different - dysthymia is responsive to SSRIs and doesn't seem to have the placebo effect like major depression does; I've also seen some distinction between early-onset dysthymia - which is usually teenage years though not necessarily diagnosed then - and late-onset - which is more likely in elderly as they get sick and immobile).

In addition to all that, there's been a lot of research on the change in the HPA-axis, which is cortisol, etc. So it is a big bundle of complicatedness that no one really knows anything definitive, IMO.

(I'm a lay person researching this stuff because if affects me directly and I have a lot of other health issues and I'm wondering what the interplay is between it all. It started with finding chronic childhood stress correlations with chronic diseases in adults (ACE study).)
posted by evening at 9:03 AM on January 11, 2015


I find the inflammation research interesting because it seems to apply to Bipolar Depression as well, which is not always the case in Depression research. I suffer from awful Bipolar Depression, and there is not a whole lot out there to treat it, so I am hopeful this research will lead somewhere. (Mania is somewhat more straightforward to treat and I almost never have to worry about mine.)
posted by Biblio at 10:06 AM on January 11, 2015


More anecdotal corroboration -

I notice that when I get out ahead of my pms with Aleve (an anti-inflammatory), my cramps AND my mood swings are lessened.
posted by double bubble at 6:46 AM on January 12, 2015


I notice that when I get out ahead of my pms with Aleve (an anti-inflammatory), my cramps AND my mood swings are lessened.

I encourage anyone who gets bad menstrual cramps to seek a prescription for etodolac, which is a stronger anti-inflammatory than available over-the-counter.

I started taking it for another condition (arthritis) last year but it also helped tremendously with my menstrual symptoms as well. I went from having awful back pain the day before my period and crippling cramps for the first 3-5 days of my period to not feeling ANY period-related discomfort at all. It's such a pain-free experience now that sometimes I don't even realize it's started until a clot of blood falls out in the shower.

My period cramps had been so bad since I got an IUD ~10 years ago that I was effectively disabled for a couple of days per month most months. Starting etodolac gave me those days back.
posted by Jacqueline at 10:42 AM on January 12, 2015


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