Saturday, April 7, 2012

Stress Kills via Inflammation (Possibly)

What a week.  And more busy weeks to come.  I've been neglecting the blog and have only now moderated several days worth of comments, so they have been published now if you were waiting.  I'm starting to feel a bit Kurt Harrisy about comments over time, but for now I am leaving them open.  For the most part things aren't too rambunctious, but I am more easily annoyed these days.  Maybe wiser?  (Not likely).

I am getting more and more requests if I know any other evo med/nutritionally interested psychiatrists around.  Folks are asking from Atlanta to Vienna.  At the moment I know of four, including myself.  Three of us are in New England and one, Ann Childers MD, in Oregon.  My only advice is to keep checking Primal Docs and the Paleo Physician's Network.  The three other psychiatrists I know of seem to be excellent, well-trained, and careful folks, for what it is worth.  If other psychiatrists want to drop me comment (I can see it and not publish it if you ask), I'm more than happy to keep a list and to ask ahead of time if you want your name released to an interested party.  We are also working on a forum for doctors to share case studies, experience, and documentation, so let me know if that would interest any physicians out there (again, can leave a public comment, or leave a comment with a note not to publish if you want to remain incognito).

Love this song (all the songs I like when I first hear them end up being advertisements for Apple.  They should hire me to spot music for them, for sure…) Come Home by Chappo (right click to open in new tab).

Now, science.  Overshadowed by events and personalities sometimes.  I'm a psychiatrist.  I'm used to that sort of thing, but it doesn't mean it is particularly fun for me.  Perhaps it is less fun, as it feels more like work.  But the journals march on, and it is finally spring here.  Lifetime exposure to chronic psychological stress is associated with elevated inflammation in the Heart and Soul Study.

(It is so uncool to post links to Elsevier nowadays, but they have my favorite journal hostage so what can we do?  Ethics only take us so far, and then we have to write a Graham Greene novel, but we are still left with what to do.  This issue is the eternal crux of clinical medicine.  My patient does not walk out of the files of a clinical trial, where all sorts of comorbitities are excluded, but my patient still has clinical depression and still wants some reasonable advice…)

I like the Heart and Soul Study.  They are on my wavelength.  The methods are solid.  All the subjects have a history of some sort of cardiovascular disease, which is important (and they are mostly male, derived mostly from the VA, so keep that in mind).  And here they have looked into people's history of psychologic stress, measured their inflammatory cytokines, and hypothesize a connection.  The connection is confirmed by many other studies linking a history of trauma (all sorts) to elevations in cytokines.

The DL is that stress is linked to bad cytokines (IL-6, TNF alpha, C reactive protein, etc.) and that stress is linked to PTSD and Major Depressive Disorder and anxiety disorders which are also linked to the bad cytokines… as is cardiovascular disease, even in psychologically healthy individuals.  In addition, there are harmful behaviors which increase the inflammatory cytokines (substance abuse, smoking), and ameliorating behaviors that decrease them (exercise, meditation, sleep) less likely to be adhered to by those who have undergone inordinate psychological stress.

Where the rubber meets the road is that higher lifetime trauma was associated with higher levels of inflammatory cytokines at baseline and 5 years later.  When the researchers controlled for psychological symptoms of the trauma (for example, PTSD or a clinical depression), the relationship held, meaning those who had undergone trauma had elevations of inflammation even if their behavior and coping seemed more normal by psychiatric diagnostic standards.  In these folks with pre-existing cardiovascular disease, higher inflammation is associated with greater risk of death and complication.

Maybe I should leave off and move to Hawaii after all...


  1. Interesting post. Similar findings on the stress-inflammation link have been reported with regards to caregivers of children with autism:
    Indeed this chap (Brian Lovell) from one of the fine Universities here in North-East England, has done quite a bit of work in this area:

  2. Aloha Dr.Deans, hope to see you here soon. However, this is paradise lost, rampant obesity, meth and other substance abuse along with all the latent effects of government intervention. Aside from that it is a pleasant 23C and the birds are singing outside my lanai. As the Island song goes “come on over”

  3. I'd like to see the study where those who have been affected by the psychological stresses mentioned have had all thing inflammation-promoting controlled (good sleep, DIET, and low daily stress). Would we see a different outcome in psychologic symptoms (would we even see these people, no complaints, no doctor visits). It's difficult to study healthy people...

  4. On my next radio show episode I'm going to be discussing an interesting paper suggesting that glucocorticoid resistance (GCR) - and not circulating cortisol levels per se - is one of the primary mediators of the stress-disease connection. In other words, high cortisol isn't the problem - cortisol resistance is. I think this is fascinating and it explains the lack of correlation between circulating cortisol levels and disease states.

    Here's the paper:

  5. Chris, that kills me because I've been avoiding tackling the whole "adrenal fatigue" issue because the depression papers suggest hypercortisolism in the HPA axis, not some sort of "fatigue" issue, and I'm looking for some physiology here to explain the masses. Not that there is physiology to explain the masses, but it would be nice.

  6. lol of course 'Come Home' became a spot for apple, it mentions iPod in the song =)

  7. Ha I might be one of the ones who makes you close down comments as this will start out a bit nit picky but I do have a question that I've pondered for awhile. Just wanted to first comment that referring to IL-6, TNFalpha etc as 'bad' cytokines is like referring to LDL cholesterol as 'bad' cholesterol. Obviously they are not bad and save your life on a regular basis.

    However this article brings up an interesting possibility that when the costs come down immunosuppressants especially the new mAb therapies (Humira, Remicade etc.) will cross over to the mainstream as preventatives.

    Which brings me to an actual question :) One thing I'm wondering is whether you have had experience with patients who end up on Humira or other immunosuppressants and if so have you ever seen pyschological symptoms improve or markedly improve just by taking these substances? (I know the arthritis, IBD, etc are massive confounders)

    And if you have seen marked improvement would you ever use any of these off label for short time periods before the lifestyle of the patient improved? (purely hypothetical situation of course)

  8. E - you aren't wrong. Stress keeps you alive in the right amount, like all hormetic stuff. And we would be dead as doornails without inflammation. I suppose I got tired of putting the quotes around "bad" but those same cytokines are pretty much always linked to depression and whatnot.

    My experience with Humira, et al is that they seem to be incredibly toxic. I think they must interfere with vitamin metabolism because folks on them are pretty miserable (actually, about every three months I get some pour soul on methotrexate who never had any history of depression before… and all I do is give them some methylfolate and they perk right up). I've never seen that with naltrexone, however, which in low doses is also an immune modulator. Makes you wonder.

  9. I plan on writing an article (or series) on so-called adrenal fatigue soon. I think there's a lot of misunderstanding of it on both sides. I guess it depends what someone means when they use that term. If I ever use it, it's simply a user-friendly way of saying what I really mean, which is HPA axis dysregulation. Kind of like IBS. It's not a real diagnosis or phenomenon, but it's helpful in conversation because most people have a general idea of what you're talking about when you say it. A time saver, if you will.

    I agree that "adrenal fatigue" is often not a low cortisol state, or even a high cortisol state for that matter. It's much more complex than that. It involves a dysregulation of the entire HPA axis, and as this latest study suggests, possibly GCR as well. In fact, "cortisol resistance" might be a more primary mediator than any changes in the HPA axis.

  10. I heard the same thing that chronic stress leads to inflammation. It goes by way of chronically high cortisol and then body becomes like "cortisol resistant". Since one of the functions of cortisol is to keep inflammation in check, cortisol resistance lead to run-away inflammation.

    Here is the article on Proceedings of the National Academy of Sciences...

  11. I'm a psychiatry resident very interested in nutrition and evolutionary medicine. Would love to participate in the forum you mentioned. I'm in Toronto and having a hard time finding like minded mentors.

  12. I hope this isn't too tangential to throw out here, but so far, haven't found anything closer:

    In Germany and a few other European countries, constitutional hypotension, whether or not symptomatic for dizziness/syncope, is treated as a causative/correlational (I'm unable to tease this out) factor in clinical depression.

    There are several large studies which show a robust linear relationship between CH and depression/anxiety, followed by depression, then anxiety states alone. Moreover, there is a recent study which demonstrated reduced brain perfusion and cognition with CH.

    Given that Paleo type diets are anti-inflammatory and often reduce blood pressure to boot, what are your thoughts about managing CH in light of these studies?

    It seems to me that this correlation makes sense. When patients are "getting shocky", they are usually notably worried and anxious. And no experienced nurse or physician ignores patients who share an impending feeling of doom. So my thinking is if the brain is continually stressed with initial shock signalling, that its response would be to heighten anxiety and depression responses which slow the person/put them in the sick role. A subconscious protective mechanism at work, perhaps?


  13. Great post - thank you! I'm a C/L psychiatrist and paleo devotee with a huge interest in inflammation links to mental illnesses, evolutionary nutrition relating to the onslaught of all chronic diseases, as well as the fascinating avoidance of these issues by most doctors today in the name of more "scientific" pursuits. I would love to participate in any forums or learning experiences including case discussions as you mentioned. I have very much appreciated your blog with the careful attention to good research mixed wisely with clinical experience. Thanks again!

  14. Laura and Paleocare - please drop a comment with your email address, ask me not to publish it, and I will email you the specifics. Thanks!

  15. Do you know any studies that look at whether adaptogenic herbs, such as rhodiola rosea, work to reduce the cytokines produced by stress? I know for a fact that rhodiola makes me cope better but whether it is working down at that level, I have no idea. Might be good to know. BTW, it was my doctor (an MD with naturopathic proclivities) who suggested I take it. She takes it herself!!! Maybe no need to move to Hawaii?


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