Saturday, May 12, 2012

Mom's Wheat Sensitivity and Offspring's Schizophrenia Risk

In the midst of all the chaos this week came a very interesting diet/mental illness risk paper.  Particularly good because it comes from the premier psychiatry journal (that we in the biz call the "Green Journal" because the cover is… well…anyway): The American Journal of Psychiatry (and looks like the full text is available for free) --- Maternal antibodies to dietary antigens and risk of nonaffective psychosis in offspring.

"Nonaffective psychosis" are psychotic disorders not related to major depressive disorder or bipolar disorder (both of which can cause psychotic symptoms during severe episodes).  The most common primary nonaffective psychosis will be schizophrenia, though there are a few other rarer disorders, such as delusional disorder.

Lest we forget who the enemy is, it is inflammation.  Yes, our immune system, in the context of our modern lifestyle is often like an group of soldiers armed to the teeth with too much to do on one hand (all these modern epidemics of infections) and too little on the other (wherefore art thou, old friends?).  Lest we forget, without inflammation, we will die.  Our immune system is necessary, just like an army from time to time.

To put the screws on schizophrenia risk, let's say now, with relative surety, that there is no single cause.  Schizophrenia isn't even a single disorder, but rather a variety of disorders with similar enough symptoms to be lumped together by that most imperfect of documents, the DSMIV.  But, a few things come up over and over when we look at the suspicious characters, and these things all go back to the immune system (inflammation), genetic risk, and those contributions to the pathology of schizophrenia (ultimately brain damage of a particular kind, a neurodegenerative disease).

Risk factors for developing schizophrenia that I've heard over the years:

Family history
Advanced paternal age (and to a lesser extent, advanced maternal age)
Infections (particularly toxo and herpes)
Birth in the winter months (could be associated with infections or…)
...Low vitamin D at birth
Complications during pregnancy or birth
Cannabis use, particularly at a young age

(before I forget, it's a beautiful day… Punching in a dream by Naked and Famous)

So we get the usual hodgepodge of genetic risk (family history) plus environmental stress (particularly severe stressors that occur when the brain is forming) = increased risk of developing the disease(es).  Ultimately at a certain stage of development (typically late adolescence for men and about 10 years later for women), brain cells begin to die, signals misfire, and we end up with the typical symptoms.

It makes perfect sense that if we have a sensitivity to something in our diet, inflammation will increase, and that risk for all sorts of autoimmune conditions and other chronic diseases will increase.  And, as we already know, there is an association between schizophrenia and celiac disease, and schizophrenia and weird wheat antibodies.

So now, the new paper in the Green Journal.  It's one of those cool studies that are only possible in Scandanavian countries where you pay 70% of your income in taxes and the government keeps tab on all your health information from birth to death.  In this case, the neonatal blood samples of a whole population of folks were collected (everyone in born Sweden since 1975) and a sample of folks later diagnosed with schizophrenia and matched healthy controls were analyzed.  IgG antibodies (immune response) to gliadin (from wheat) and casein (from milk) were measured.  Newborns have immature immune systems and do not make IgG antibodies.  These antibodies must have been made by the mother and passed through the placenta in the late stages of pregnancy to the baby.

Don't all run out and get expensive IgG tests to see if you are "sensitive" to foods.  I've never seen anything compelling to show me these tests were a reliable indicator of allergies.  Wheat is so commonly eaten that almost anyone with an inflamed or "leaky" gut will have IgG antibodies floating around… however, in this study, it was the 10% of folks who had the highest IgG signal to gliadin whose offspring had increased risk of schizophrenia.  IgG antibodies to casein were not linked to any increased risk.  If only the 5% of babies with the very highest levels of IgG antibodies to gliadin were consider, the odds ratio of developing schizophrenia later in life jumps to 2.5.  Don't get me wrong, the absolute risk will still be pretty low, but any time an odds ratio jumps to >2 one should prick up one's ears as it is an interesting finding.  These findings were not attenuated by adjusting for confounders.

In general, a highly positive IgG test to gliadin means you have a risk of having celiac disease (though it is not one of the standard tests, which are typically measures of types of HLA genes, anti tissue transglutaminiase, and IgA to gliadin).  Did the moms with the highest IgG in this study have untreated celiac disease, and thus a fully flowered autoimmune disease with all the inflammation on board, affecting mom as well as fetus?  Sure, except full blown untreated maternal celiac disease is typically associated with malnutrition and small birth weight, whereas in this study there was no correlation between high anti-gliadin IgG and low birth weight.  In addition, while 90% of folks with celiac will have the HLA-DQA*0501 and DQB*0201 alleles, these alelles are not increased among folks with schziphrenia. 

All told, once again we have a link between wheat and schizophrenia, one not explained by celiac disease alone.  More unveiling of the connection needs to be done.


  1. One risk factor is missing from your list: mineral deficiencies. This seems to be a taboo subject among brain scientists, at least here in Oxford. But sensitivity to wheat and the structural abnormalities seen in schizophrenic brains are both arguably caused by mineral deficiencies. Not of iron, zinc and calcium; we actually have too much of those. Manganese, copper and magnesium, which are antagonists of iron, zinc and calcium respectively.

  2. I have heard a lot of bad things about gluten and I believe many people have gluten sensitivity to some extent more or less. For those with full-blown celiac disease, they should not consume even a single drop of it. But for those without full-blown celiac that wants to avoid the toxic effect of gluten, can benefits be achieved by limiting gluten? Or does one need to eliminate it completely in order to see any benefits at all? Some say "all or nothing", others say there is a dose-sensitive effect.

    1. I think for most people without celiac (particularly celiac, where each molecule is very dangerous), or other gluten sensitivity, gluten can be eaten in moderation without too much of an issue. Though of course I don't like grains displacing other more healthy calories, myself (and those who have the patience to prepare certain grains properly can get some real good nutrition out of them), I'm not going to begrudge most the occasional slice of pizza or birthday cake. It's not a daily indulgence for me by any means.

  3. Jane has a point: manganese is the active-site mineral catalyst for the peptidase enzymes that hydrolyse prolamine bonds. A deficiency of managanese (or an enzymatic polymorphism that decreases manganese utilization at low intakes) would result in gliadorphin and beta-casomorphin7 surviving in the gut. The persistence of prolamines due to incomplete digestion must surely be an early trigger for autoimmune sensitivity to them. Elevated levels of interferons seem to be another.

  4. This sounds like something that is simple enough to get a rough handle on: what are rates for schizophrenia in mainly or exclusively rice eating cultures, compared to much less rice eating cultures? Or non-grain eating cultures, if such a culture exists? Of course, not all countries or locations collect the necessary information, or do so in any helpful way.

    What is very interesting is that it does not seem to relate to gluten/celiac directly. For that matter, it may be some yet unsuspected part of the wheat protein.

    Maybe pregnant women should avoid wheat?

    1. Though Dohan thought there was an increase in schizophenia in wheat-eating regions, every big name lecturer on schizophrenia and worldwide trends I've ever seen, including some of the foremost researchers in the world, mentions the remarkable similarity in the incidence of schizophrenia (approximately 1%) everywhere.

    2. I spent a few minutes reading on Dohan, and it seems reminiscent of Weston Price: a guy that comes along early, gets things right, and is overcome by the conventional wisdom, such as it is, and "paid for" science. This is not an unusual scenario, when you consider market forces and the lack of repute and low regard accorded to nutrition based causes for illness. I mean, isn't mental illness properly treated by the (lifelong) use of drugs? Don't we all know that? And another example: How well does Vitamin D work on cancer?

    3. If this is true wouldn't it instantly disprove a wheat / immunological mechanism?

      Although isn't it also true "schizophrenia" is a huge disease with paranoid and disorganized and generally no similarity between subtypes other than the fact patients are all typically young, more often male, and irrational/crazy totally?

      I've heard that disorganized / catatonic schizophrenia relates more to maternal malnutrition and starvation, and prenatal infection, whereas other forms of mental illness like paranoid schizophrenia may be more related to the environments found with prosperity. If rates of schizophrenia are stable at 1% all over the world, it might be possible that these are very different types of schizophrenic patients, and totally different pathophysiologies...

      I do tend to eyebrow raise the "1% everywhere" statistic as it seems to contradict other evidence such as catatonic schizophrenia is less common in prosperity and maternal overnutrition.

    4. Woo--I agree that the different subtypes are all lumped together, and we are really talking about different diseases with a similar common endpoint (thank you, DSMIV). Hebrephrenia and catatonic schizophrenia are vanishingly rare nowadays, but was a major subfraction (I think 30% were hebrephrenic, and fewer catatonic but not an insignificant amount) in the very careful descriptions by Schneider and Kraepelin and those guys, of thousands and thousands of patients. That was the late 1800s and early 1900s, the heyday of industrialization of some food and white bread without fortification.

  5. IMHO it's knackered guts that's the main problem, rather than the types of proteins that are eaten. That said, eating excessive amounts of slow-to-digest proteins (e.g. glutens, casein etc) is asking for trouble even in people with guts that aren't knackered.

    See Physiology and Immunology of Digestion

    Jamie has blogged quite a bit on what knackers guts, as have I.

    1. The lack of association with casein makes me suspicious it really is partly a gluten issue, but you're right, and I hate IgG alone partly because it doesn't tell you as much as combinations of inflammatory markers and whatnot will. But they were working from old bloodspots so what can you do?

  6. This whole epigenomics issue is scary in light of the dreadful diets people have had for the past 100 years. Are we going to have a tsunami of neurologically damaged children (special ed.) because their grandparents ate Twinkies and other garbage.

    1. The diets of the early industrial age were pretty horrendous. How did we turn out?

    2. But Emily, it seems to me that the bad diets are getting worse and more widespread. Low fat nonsense is everywhere and raw milk drinking is being squashed by the FDA.

    3. We have overnutrition and seed oils and processed grains… but most of us aren't rampantly vitamin and mineral deficient, as we have been in times past. Our health is not optimal with the modern diet, by any means. (and lest anyone be confused by my answer to another comment, I don't think wheat is a health food. I personally put it in a group with candy. It's fun to eat sometimes, it's not going to ruin your gut forever should a molecule pass your lips, but some of us are extremely sensitive or allergic to components of it and should avoid it always).

  7. Emily, my comment is not related to this post, but I don't see how to email you. I read this article today Very sad and disturbing, and I wonder if any research has been done on the diets of these children. With my limited knowledge, I have to wonder if the epilepsy diet (90% fat) would lead to any improvements. I would love to hear your thoughts.

  8. Wherefore actually means why or for what reason, not where.

    1. Oh, I know. Are the old friends not a philosophical representation of the whys and wherefores of evolutionary medicine?

  9. Perhaps the incidence of schizophrenia really is everywhere the same, except in the West, where better nutrition, antibiotics, and protective obesity are bringing it down; except in the case of wheat eaters, who don't benefit from that protection; so the rate is the same after all...
    Wheat decides, in part, which people with schizophrenia genes will get them activated.

  10. Hi Emily -

    If inflammation is, indeed, the mechanism of action does this raise the possibility of prophylactic administration of anti inflammatory agents during pregnancy to mitigate developmental risks?


    Of course, such an action with be fraught with other unknown risks, but as a society, we seem to have replaced infection with inflammation, this might be something to consider.

    - pD

  11. This is a little off topic, after reading the first comment I wanted to share a personal observation I had recently. I've been taking Ambien for years for insomnia possible in part because I have restless leg syndrome. I recently decided to wean off the Ambien even though the only side effect I had from the Ambien was good restful sleep. I decided that I was going to supplement with some L- tryptophan and then add in some Melatonin to help me to wean off, but I also decided to try Magnesium. The first night I took the Magnesium my legs felt "quiet." My legs always feel achey, jittery, but after the Magnesium nothing and it last most of the day also. I'm down to 2.5mg of Ambien and I don't really think I need that. I'm sleeping like a baby and my feeling is that it's more the Magnesium than the melatonin or the L tryptophan.

  12. Testing for casein antibodies doesn't tell you whether someone is sensitive to casomorphins or other prolamines. If you're looking for antibodies to suspected food triggers, shouldn't it be the digested forms you look for, the commonly found or suspect products of partial digestion?
    (So I would largely discount IgG testing for gliadin or casein sensitivity because it will under-diagnose amongst the wider array of possible antigens arising from these proteins. The opposite reason from you, perhaps.)
    This finding re: gliadin might just be the tip of the iceberg.
    Unless it is handling, not eating, wheat that causes the problem...

    Another reason why lower rates of schizophrenia might be expected in the developed world is lower stress.
    Fewer suicide bombings, genocides, drone attacks, famines and all that.
    Also, I've known a few schizophrenics in my life and I don't recall any of them being fat (before the psych drugs).
    In fact, if there is one psychosis trigger I would single out from my experience, it is suddenly not eating for some reason.

  13. '..most of us aren't rampantly vitamin and mineral deficient as we were in the past..' Actually we might be. According to official Recommended Daily Allowances, we aren't. But suppose they're wrong? The RDA for copper in the US was recently set at exactly the level found by Leslie Klevay to cause symptoms of heart disease in volunteers. He and many other copper researchers believe MOST OF US have copper deficiency, which is implicated as a major cause of heart disease. Without copper, iron cannot get out of cells, and iron overload is implicated as a cause of practically everything.

  14. Have a look at this from The Saccharine Disease.

    "Regarding mental disease in the people of the Transkei, I can say that in the past 11 years I have not diagnosed a single case of schizophrenia in a tribal African living on an unrefined carbohydrate diet, whereas this disease is the commonest psychosis among the urbanized Africans." Letter from Dr Daynes dated September, 1971; p25


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