Odd wheat immune reactions are found in folks with bipolar disorder.

Not too long ago I wrote an article on the possible links between wheat and schizophrenia.  It turns out that intrepid investigators have been looking at connections between wheat consumption and other serious illness too, such as bipolar disorder.  While there is nothing that would definitively prove wheat causes bipolar disorder, the research findings raise a lot of questions that we should really look at more closely.  So let’s dive in.

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 as part of a bigger clinical picture. It is not the disorder unless the symptoms are bad enough to get you into some serious trouble. You might spend too much orsleep around too much, you don’t sleep, you are possibly more religious and grandiose – in cycles, often alternating with depressive episodes. Another form of the illness results in the occasional hypomanic episode amidst a lot of chronic depression.

It is important to know that bipolar disorder is associated with inflammation and metabolic syndrome (1), diabetes (2) and a“western” style diet.  I believe that a combination of chronic stress, genetic vulnerability, nutrient deficiencies, and food toxins (including gluten) are responsible for most of the chronic disease in the western world, including mental illness.  To put it another way, 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.

So if wheat possibly plays a role in the etiology of schizophrenia, why would we look at bipolar disorder, which is an entirely separate diagnosis?  Well, it turns out the two disorders 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).  This new paper by Faith Dickerson’s group  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 (antibodies to specific types of wheat proteins) compared to controls, but there weren’t really differences with respect to tTG and IgA gliadin antibodies which are typically elevated in celiac disease.  So what we find is that people with celiac, bipolar disorder, and schizophrenia all have weird immune responses to wheat that healthy people don’t seem to have.

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 the wheat protein gliadin means one has a sensitivity to gliadin.  Al a positive IgG test means is that your blood has been exposed to that protein and you made an imune reaction to it.  Could be you sliced your finger while cutting a loaf of bread or something.  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, so lots of proteins are getting through and are exposed to your immune system. Gliadin is a pretty 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, a milk protein) consumption was from this nifty study in autism (6), where the kids on the gluten-free/casein-free diets had pretty tight junctions in their guts (so no leakiness), especially compared to the autistic kids and their relatives. However, the study was small and the link is awfully tenuous.  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).

So all we have is a mystery – why the strange immune reaction to wheat? 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 bad inflammation associated with the 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 th dairy protein 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 (another one from Faith Dickerson’s group, as a matter of fact):

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.

About Emily Deans, M.D.

Emily Deans, M.D., is a board certified adult psychiatrist practicing in Massachusetts. She graduated from the University of Texas Southwestern Medical School in 2000 and from the Harvard Longwood Psychiatry Residency in 2004, and was a Chief Resident at Brigham and Women's Hospital in Boston. She is currently a Clinical Instructor in Psychiatry at Harvard Medical school, though this blog has no affiliation with and does not necessarily reflect the opinions of the institution.

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