More on Wheat and Serious Mental Illness

All right.  Tuesday.  Yesterday at noon local time a big earthquake hit Christchurch, and all of our good wishes are with the people there, especially as one of Evolutionary Psychiatry's best internet friends is Jamie, who lives smack dab in the middle of Christchurch.  Here's a link to the New Zealand Red Cross if you would like to lend a hand.

Before disaster struck, Jamie was kind enough to send me a link to a new paper (free full text) about Bipolar Disorder and gluten markers.  The paper doesn't give us much, but it does stir up some good ol' murk.  So let's investigate.  Bipolar disorder is an illness of mania or hypomania plus or minus depressive episodes.  Bipolar disorder does not equal "moody" or "irritable," though those can certainly be signs.  It's not the disorder unless the symptoms are bad enough to get you into serious trouble.  You spend too much, you sleep around too much, you don't sleep, you are more religious, you are grandiose - in cycles.   And, of course, it is associated with inflammation and metabolic syndrome (1), diabetes (2) and a "western" style diet. 

I have suspicions about those links.  I'd bet a monkey that a combination of sugar, trans fats and vegetable oil, and high doses of refined wheat products (as I've mentioned before, the evidence against wheat is circumstantial) are culprits behind metabolic syndrome and diabetes.  And maybe a subset of the population suffers at the brain level too and manifests bipolar disorder.  Hey, seems as good a theory as any. 

Wheat has been investigated on and off over the years as a culprit in schizophrenia.  And bipolar disorder and schizophrenia can overlap sometimes in symptoms - while depressed people can be psychotic, a frank manic psychosis will look pretty much the same in the hospital as a schizophrenic psychotic episode, and there may even be some genetic overlaps (3)(4).  The new paper that Jamie sent me is the first to study celiac and wheat-associated antibodies in bipolar disorder.  In schizophrenia, there is a definite increase in wheat-associated antibodies in the serum (5) and these antibodies aren't the same ones that are seen in celiac disease.  Well, with bipolar disorder, seems the same thing is true.  Bipolar folks had a significant IgG gliadin reaction compared to controls, but there weren't really differences with respect to tTG and IgA gliadin antibodies which are typically elevated in celiac disease. 

Ooh ooh ooh, wheat is BAD.  Well, probably, for various reasons.  But, of course, I don't necessarily believe that a positive IgG test to gliadin means one has a sensitivity to gliadin.  I griped about IgG food sensitivity tests not too terribly long ago.  I think a robustly positive IgG test to lots of things means one may have a leaky gut.  Gliadin is a pretty darn common thing to eat, so folks with leaky guts may come up positive for gliadin.  The most robust evidence in humans I've seen for leaky guts linked to wheat (or maybe casein) consumption was from this nifty study in autism (6), where the kids on the GF/CF diets had pretty tight junctions in their guts, especially compared to the autistic kids and their relatives.  Boy, I bet the researchers have really pounced on this diet and mental health link and studied leaky guts in bipolar disorder (7)(9)! Er, no.  But, links have been found between major depressive disorder and leaky guts (8 - an interesting enough paper for another day).

Like I said, murk.  Best I can consolidate from all this information - it may be that folks with bipolar disorder have gut issues, and gut issues are inflammatory issues, and a higher IgG response to gliadin occurs, and inflammation causes the body to release cytokines and general badness, and those cytokines may predispose the genetically vulnerable to psychosis.  Also, there may be particular ick associated with exorphins in wheat being neuroactive.  And is it just wheat?  There's a paper linking recent onset psychosis and schizophrenia to IgG and IgA antibodies to casein (10).  In this study, the severity of psychosis was linked to the level of antibody response to casein (actually, the alpha and kappa subunits moreso than the beta, which is interesting, though first onset psychosis had a robust immune response to the beta subunit).

And I'm not entirely off the wall here, because here is an excerpt of the discussion from paper 10 -

We can speculate that a subset of individuals with recent onset psychosis and/or schizophrenia may have cellular junction pathology that allows peptide fragments generated from the digestion of bovine milk to permeate the intestinal tract, and enter the bloodstream... Dohan... hypothesized that the aberrent proteolysis of milk and grain products may produce small neuroactive peptides that can enter into the circulation and ultimately cross the blood-brain barrier.

So, lesson number one.  Don't have a leaky gut.  Lesson number two.  If your gut is leaky, best to avoid creepy neuroactive peptides.  Lesson number three.  There is nothing horribly definitive here, but plenty to study.