Thursday, November 4, 2010

Depression, Flu, and To Do

Why not a song to start? Right click in new tab if you want to hear it - alternative rock and peppy! Pumped up Kicks by Foster the People.

When I started this blog way back in June, I was worried about a lack of material. Paleo psychiatry? There's no data, I thought, or nothing solid enough worth writing about. Not a single controlled trial of any diet intervention (other than omega 3 pills or vitamins) that I'm aware of. It's no type II diabetes, where diet interventions are studied to the extreme. I figured I could throw out the basic info and write up a bit on the omega 3 fatty acid trials of depression and bipolar disorders, maybe speculate a bit on eating disorders, and then I'd be scraping for more. I'd likely move on to paleo psychology and talk about how preserving sociopathy in the gene pool keeps our species tough and ready to fight. Well. Here we are. Ninety-two blog entries later. New biology stuff arrives in my email and in the comments on a daily basis. My more immediate plans include wrapping up the Alzheimer's series with a post on some of the infectious cause papers - though Alzheimer's stuff comes out every hour so I doubt it will ever be wrapped up, digging into the thyroid, and more about mental illness and obesity/metabolic syndrome (huge topic), not to mention diving into sleep. In between that the papers come out, and keep coming. I'm like a kid in front of a fire hose.

Today another paper from the Journal of Affective Disorders. "Associaton of seropositivity for influenza and coronaviruses with history of mood disorders and suicide attempts." I like the Journal of Affective Disorders. It's edgy without being desperate. The Anna Sui of the psychiatry world.

The paper starts out with some depressing statistics - mood disorders are expected to be the second leading cause of global disease burden by 2030 (medical students - psychiatry is a promising field), and nearly 21 million adult Americans have a mood disorder. A mood disorder (such as major depression or bipolar disorder) is (obviously) a major risk factor for attempting suicide.

Guess when the "busy season" is for psychiatry. Not the summer! That's true. Most everyone is happy in the summer. But when is everyone really depressed? Wrong! It's not during the winter holidays (northern hemisphere winter, that is). We actually get the most emergency phone calls in September, October, the end of February, and March, when the amount of light changes exponentially day by day. Fall is bad, but spring is much, much worse, and that's not something I would have predicted before residency. Beware the Ides of March.

Springtime is also the busy time for the flu. And seasonal suicide peaks overlap or closely follow seasonal peaks in epidemic influenza and upper respiratory viruses. (These peaks also happen during the yearly nadir of vitamin D levels, don't you know?). I've certainly noticed that my patients with depressive and other mood disorders tend to be down for a few weeks after recovering from a cold or flu. Apparently I'm not the only one who has noticed - back in 1892 Tuke wrote up a series of "post-influenza mania and depression" cases admitted to a London hospital.

So what did the researchers do? They took 257 subjects, mostly female, including 39 healthy controls. They were already involved in a study on environmental influences on exacerbation of mood disorders and suicidal behaviors. (It is perhaps not well known that all scientific research is in fact done on some thousand-odd college students and ex-hippies who are amenable to being recruited for study after study from the same medical center). These participants met criteria for major depressive disorder or bipolar disorder (or were controls), and answered questionnaires about their suicide history. Then they gave some blood, and the blood was examined for seropositivity for previous infection with several viruses, including influenza.

And guess what? People with previous flu and coronavirus (a common cold virus) infection had a much higher chance of having major depressive disorder. We're talking p=0.004 and p< 0.0001 for influenza A, B, and coronoavirus, so highly significant. Previous infection with influenza B was significantly associated with a previous suicide attempt as well (p=0.001), with an odds ratio of 2.53. Influenza B also seemed to increase the risk of having psychotic symptoms in mood disorder patients. Coronavirus and influenza A didn't seem to increase the risk of suicide or psychosis.

Wow. Okay. You mean these "mental" diseases might be biological?!? Immune response to the flu and other viruses involves cell-mediated immunity and a flurry of cytokine activation. Turns out those same things are active in the biological cascade of depression. The same old interleukins and TNF-alpha are involved in everything. Cytokines tend to make tryptophan into kyrunetic rather into serotonin, and that is not so good for the mood, and even worse for suicide. Influenza and coronoviruses are also possibly active in the brain itself, but the evidence is a little sketchy.

I have to admit, during medical school in residency I never got my flu vaccine. I didn't remember ever getting the flu before, and I washed my hands plenty, so hey... once I had kids, I got my yearly shot. According to a presentation I attended back in April, 10-20% of adults will never get the flu. They are lucky, or especially immune. The other 80% of you - here's something to think about. And ratchet up that vitamin D. Can't hurt.


  1. GREAT song. Oh, and interesting post!

  2. Makes one wonder what's cause and what's effect. Does infection make us more susceptible to depression? Or does depression make us more susceptible to infection.

    Perhaps the truth here is that there's another fact that causes both and so accounts for their correlation. Is that what you meant with the final comment about vitamin D? Does D deficiency (and perhaps other micro- and macro-nutrient abnormalities) cause a host of problems, among them susceptibility to disease and depression? That would be good, because if true we have the ability to alter the root cause. We can control what goes into our bodies.

  3. Hi Emily,

    I'm a 62 degree north University student, so I've seen somewhat depressing amounts of depressive symptoms in students for sure. It's the darkest period right now without any snow, the lenght of the day is only merely 8 hours and the sun raises only 30 or so degrees. Not fun.

    I recall even sociologist Emilé Durkheim noted that suicides spiked during march/april. The spring thing remains really intriguing.

    You said:

    "The same old interleukins and TNF-alpha are involved in everything."

    You Betcha. I have Crohn's Disease and the last resort treatment for IBD (and rheumatoid arthritis) are TNF-alpha antibodies. I haven't tried those and hopefully won.'t since D3 "cured" my Crohn, so far. But the mechanisms seem so obvious. Teeth infections, depression, anxiety and other mood problems just seem so simply an inflammatory cascade, which of course if treated by immunomodulalatory drugs, D3 is "dangerous" after all.

    Don't know about clinical depression, but I could name around 20+ people that got TREMENDOUS +++ from adding D3, both Colitis and Crohn's patients, much more than Omega 3 actually. Someone should do a big trial.

    What do you think on theory about serotonin and T cell responses ?

  4. this can't be stressed enough: "I could name around 20+ people that got TREMENDOUS +++ from adding D3"

    i'm still just talking from my experience, but again, if i take 20'000IU D3 (which is still in the upper physiological range btw) and basically get the same very strong brain boost and mood lift as from a classic antidepressant, what does that mean? i now believe most lethargic and unhappy people should the fuck BATH in liquid vitamin D3 for a week!! give every patient a bottle of a K1/K2 combo, magnesium, zinc and a bottle of 10'000IU pills (2 to 3 a day), and get him/her into the upper range of optimal D, like 80-100ng, asap and see what happens! i bet for most the result would be extremely positive.

  5. Franklin - I'm sure there are many people out there who have a clinical depression who have never had the flu, maybe even some who haven't had a coronavirus cold. So the flu is not THE cause of depression, but it is plausible that the infection and immune response to the illnesses will set the stage for the long-term inflammation that is a depressive or bipolar disorder in the brain. In addition (and this is totally my speculation here), influenza B may even set the stage for an autoimmune attack or something more serious in certain parts of the brain, predisposing one to suicidality and psychosis. Vitamin D, as it reduces flu infection, would therefore plausibly be a helpful agent in preventing depression.

    Neonomide - I've been disappointed by vitamin D and depression. I have many patients now at mid 50s levels who are struggling as hard as they ever were. I have to say, though, that there seems to be a certain pale, slightly bloated and fatigued look (similar to a hypothyroid look) in people who have an extremely low vitamin D - less than 15, that goes away after a month or two of daily supplementation.

    The serotonin/T cell link is concerning, and I'd never heard of it before. There needs to be more research about such things (I'm not aware of any) - however, the post-synaptic serotonin receptors are down-regulated during SSRI treatment suggesting compensation, and SSRI treatment seems to *decrease* the cytokines and other factors of cell-mediated immunity (according to work by Maes), so I'm hopeful we aren't causing a host of autoimmune disease with antidepressant treatment.

    Qualia - I think that once the body is fairly replete with vitamin D, we only absorb about 4000 IU a day through the skin - prior to that it is usually more like 12,000 (but can be as high as 22,000). I know one of the vitamin D researchers gave folks a shot with 100,000 IU D3 at one time for seasonal affective d/o and it seemed to help. The 500,000 in 10 days in the nursing homes doubled risk of fractures in the recent JAMA study, but obviously they didn't supplement with K2. I also was reading a (clever but very speculative) essay by an MIT researcher who was concerned at high doses of oral D3 in the gut - that it might be harmful to our flora and fauna. That's why I prefer to go rather slowly with my recommendations for patients (generally 2000 IU daily for three months, check a level, then adjust from there) - many people I have checked at this point get up to the 40s or 50s no problems with 2000 IU daily. Some people require 4000 or more daily. My target is also 50 for a blood level - there are some reports of lifeguards with levels of 80 but not much higher, and the lifeguards with high vitamin D levels seemed to have a higher risk of cardiac issues... it seems to me that 50 seems to be a great level to reduce risk of cancer and other issues without the risk of going too terribly high. Caucasian pregnant women did better at 60, though - something to consider. Without all the information and with such powerful, pleiotropic effects, I am a bit conservative with respect to D (though not as conservative as most doctors).

  6. emily, i completely understand that you need to be a bit conservative with your approach - so would i as a doc i guess. that's the nice thing about self-experimentation - if i mess up, it's "just" my own health, and at least i know who to blame *g*. i also agree that usually lower doses may be enough to bring an otherwise healthy person into a normal range. interestingly, in my case, 3 month of 5kIU, and another 3 month on 10kIU didn't even manage to get me over 24ng/L - which is interesting. i reckon that this is either because of limited absorption due to gluten intolerance, or due to a chronic infection (or sarcoidosis), which theoretically could cause the concerned tissue to instantly convert the D3 into active 1,25 D3 for fighting the pathogen (that was a theory mentioned by paul jaminet, which is supported by some research). this was the reason i was thinking, f*ck that, im doubling the dose again, and went to 20kIU. i don't have the new blood level yet, but i know that i FEEL the D3 working now. it could very well be tho, that *my* 20kIU is just another's person 10kIU, biologically speaking. so, i guess that all those dosages and blood levels are probably pretty relative in the end, and need to be adjusted on an individual level due to absorption and receptor genetics etc, similar to the *how one looks, feels, and performs* approach by robb wolf heh. so, to summarize, my recommendation now would be to double the D3 dosage every few days until someone that was deficient before (say, <20ng) actually FEELS the D3 working (usually in the brain, i guess), and stay there for say, 2 months and then retest. afaik there is no case of harm known under 30'000IU/day long term. that would be the max dosage i would take or recommend if it's for more than a few weeks anyways. for acute infections, i found the recommendation by mercola quite interesting as well: "You can also use vitamin D therapeutically to TREAT the flu. The dose of vitamin D you can use would be 2,000 units *per kilogram* of body weight. The dose would be taken once a day for three days. This could be a very large dose if you were very heavy (2-300,000 units per day). This is the dose that Dr. John Cannell, founder of the Vitamin D Council, has been using very successfully for a number of years." so 200-300kIU/day for 3 days! quite the progressive recommendation for a doc heh ;)

  7. Hi Emily,

    I've been debating about whether or not to get a flu shot this year and saw your comment that you get the vaccine now that you have kids. Don at Primal Wisdom believes that they may be damaging to one's health. I thought it would be interesting to hear if you might be willing to provide a counter to the idea they could be worse than the actual flu?

  8. Hi Nick - evolutionary medicine has caused me to question a lot of the basic tenets of medicine. However, I still think the benefits of vaccines outweigh the risks. I was in medical school when some of the vaccines against the major bugsnthat caused meningitis came out - in one year the cases of H flu meningitis dropped from common to zilch. That's deaths and brain damage and hearing loss averted. My kids are 3 and 1.5 and have never had an ear infection (knock on wood) - maybe because they've had an S. Pneumo vaccine? Some of the arguments against vaccines don't make sense - a single grain of pollen has a zillion antigens and we are exposed to antigen after antigen on a daily basis - it is hard to see how vaccines would be worse. Seasonal flu vaccine is really the only one now that has thimerisol (mercury) so far as I know, but given that (speculatively) exposure to influenza B may cause permanent brain damage leading to greater susceptibility to depression, suicide, and psychosis... I think I'll pick the vaccine over the illness. 30,000 people a year die from the flu in the USA (h1n1 last year was actually far less deadly than usual). I don't think it is an illness to trifle with.

  9. Emily, thank you for your very thoughtful reply. Your reasoned approach is appreciated, particularly when it seems that it is the fashion to be contrary on many of the paleo and low carb blogs without always using critical thinking. I don't mean to single out any particular blog, I enjoy most of them, but often feel that the thinking on a subject can become circular.

    Thanks again.

  10. Interesting topic. I know from personal experience and from some anecdoatal reports that for some depression seems to significantly lessen when the person in question is sick. This is so weird because you'd think the opposite would be true. But I never really paid much attention to how I felt in the weeks after recovering. The study adds to my belief that something biological (beyond simple brain chemistry) is influencing depression symptoms.

    1. Yes! I see this as a key hint to solving my "depression" case: I feel mentally fine--relief comes--when I catch a cold (or the flu). I've read a couple of comments over on the Jaminets' perfecthealthdiet site saying the same thing. Must stay focused on this hint, lest others around me tell me it's my cognitive habits causing this neurological disorder.

  11. Just want to say thanks for the blog.... the song felt good, too!

  12. (Belated) thanks for this blog. I had the flu shot on Thursday and suddenly wept for no reason through Friday evening and was down through Saturday, though that might have been partially due to Cumerbatch's portrayal of Turing. I can only put it down to the vaccine but I could find few objective sites explaining a possible link (beyond the 'all medicine is bad' rants)


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