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.
I think part of the reason the gluten-psychiatric illness connection is still somewhat murky is that the testing for gluten intolerance has been limited to alpha-gliadin and TTG4. But there is also beta-, gamma- and omega-gliadin, and 7 other types of TTG, WGA, glutenin, gluteomorphins and deamidated gluten. Researchers have only recently begun to test for these different epitopes of gliadin and compounds in wheat, and already we're seeing that the incidence of gluten intolerance when all of these are included is much higher than previously thought - and the consequences are more varied and serious.
ReplyDeleteHi Chris - glad you mentioned that, because I think it is a vital point and I meant to reinforce that more in my post - if you look at the reference for paper 5, with schizophrenia they did a neat study where they mapped reactions to any wheat-associated proteins, it was really very cool. I wish they had done that with the bipolar study or the first episode psychosis studies. At least the casein studies mapped out the different subunits anyway!
ReplyDeleteRegarding bipolar I find this interesting:
ReplyDeleteWhen Hashimoto’s is misdiagnosed as bipolar disorder: A patient’s story
Well I guess Datis Kharrazian has a thyroid-centric view of the world, but that depression with thrusts of mania in bipolar might actually be hypothyroidism with thrusts of hyperthyroidism is a viable hypothesis (no pun intended).
And Wolfgang Lutz suspected that carbs (well, if you eat something like the SAD then carbs are synonymous to cereal-grains) are harming the thyroid. And we now know some mechanisms (like WGA and Gluten) by which grains can cause autoimmune diseases.
So thyroid autoimmune disease (plus maybe inflammation, plus maybe direct opioid action of gluten-metabolites on the brain, plus maybe genetic disposition, plus maybe social factors and plus maybe other disease vectors) => bipolar?
I think it is murky because we don't have a single disease-agent causing a single disease (like I don't know, lead-poisoning or say a fractured bone after a blunt trauma).
Hi Emily and co - first time caller (love your blog). This whole area of gluten "sensitivity" and psychiatric presentation is of great interest to me (particularly in connection to autism spectrum conditions). Faith Dickerson and her team have been leading the way on looking at various conditions related to cereal grains (previously schizophrenia, etc). The mechanism of action is still up in the air: some people diagnosed co-morbid coeliac (seroloy, biopsy, DQ8 & DQ2 heterodimers) but the vast majorty not. I attach a link to a recent study on non-coeliac intolerance related to IBS (I know it is slight outside of psychiatry) - in the full-text they also suggested some potential role from gluten exorphins given all the (-)ve results for CD, inflammation, etc. but did not test it. Looks like the late Curt Dohan might have been right after all?
ReplyDeletehttp://www.ncbi.nlm.nih.gov/pubmed/21224837
And combine this with the One True Pathway link I mentioned to you on your last post (igf/insulin overload up and down regulating serotonin/dopamine) and you have a fairly powerful case against a high carb diet (with insulin inducing grains and sugars) in respect to mental 'illness'. I think of wheat as the double whammy - it raises the insulin and it perferates the gut! In fact a conspiracy theorist might have you believe that patient aliens dropped wheat into our diet and are sitting back just waiting ...
ReplyDeleteOne more thought, having a thyroid causing "manic" or "drive-inhibited" phases and a n-6/inflammation causing "depression" or "non-depression" phases would explain the mixed episodes.
ReplyDeleteI think bipolar with mixed episodes is two diseases "coinciding" and one has to distinguish between depression and drive-inhibition in bipolar. No mixed episodes and no depresion, just mania and drive-inhibition would mean "pure" bipolar (without major depression).
I'm still waiting for my genetically modified, inflammation reducing, happy drug secreting, gut critters. Helminths would do nicely. Oh, and if you ask your average M.D. they will insist that inflammation has nothing to do with depression. It's all in your head...... as if my liver wasn't sending stuff to my head.
ReplyDeleteAfter reading this post I am willing to reconsider the dietary hypothesis as a factor in my endogenous unipolar depressive disorder despite what one would consider a very nutritious and strict Mediterranean diet with a preference towards organic homemade foods.
ReplyDeleteAugmentation therapy with Quetiapine and Clomipramine following SSRI and Amitriptyline-resistance has reduced my symptoms significantly, but the bane of my illness is the cyclical alternating pattern of 1-2 weeks relatively symptom free and 4-5 days of now very mild symptoms.
Basically Dr. Deans I'm wondering whether this pattern has showed up in your clinical experience, whether it is indicative of food-related cause we have thus far missed, and whether a ketogenic diet would be suitable (though admittedly I'm unwilling to drop the rye & spelt organic sourdough.
Very grateful for your feedback!
My child, whose autism drastically improved on the SCD (A grain-free diet for damaged gi-tract) also had quite an IgG food allergy rap sheet, as did I. Doctors, however, refuse to acknowlegde there is such a thing as leaky-gut. His autism was regressive and he lost his speech after spending a month on anti-biotics that gave him butt scalding diahrea. They refuse to acknowledge that there is any possible link, any at all. It's nice that we can discuss things like this, but with a medical community that continues to turn their backs and say this is all voodoo, what is ever going to become of this info?
ReplyDeleteHi all - yes the thyroid is angle is intriguing, but I doubt it is the whole picture.
ReplyDeletePangolin - yes, most docs don't know that depression is a form of inflammation. Many think it is still a matter of pulling yourself up by your bootstraps. Most are not quite that clueless, but have little patience or time for dealing with it in a holistic manner.
Santino - I don't have a whole lot of clinical experience using diet alone as an antidepressant. By the time someone is referred to me, they are generally in pretty desperate shape, and most people are unwilling or uninterested in changing their diets. BUT, I always mention it as an option and an important piece of the puzzle, and I have a whole sheet on "nutrition for optimal mental health" that I hand out to everyone. Plenty of people have emailed me or commented on their experiences with improved mood on a paleo diet, however. But many also do better with medication, stress reduction techniques, mindfulness and exercise. Many require all of that in order to start feeling normal.
Mrs. Ed - It's hard to believe in a leaky gut without evidence. But now I've seen some good evidence for it, and plausible biological reasons for wheat to cause it. I'm very glad your son improved on SCD - the more doctors who see the improvement, the more we are going to pay attention and do the appropriate research. I'm gratified that I have a number of MDs, medical students, and therapists following me here and on twitter.
Interesting blog! A friend on Live Journal linked to it, and I'm very happy she did. A friend of mine suffered from bipolar disorder for years, it got so bad she didn't manage to take care of her son - so her mum stepped up to the plate and took care of him. He was very weak and failed to thrive, and through rigorous testing he was found to be gluten intolerant. Not celiac didease, but serious intolerance. And so they tested mum too. Guess what? Gluten intolerant. They checked grandma as well, she'd also struggled a bit, but managed fairly well. Gluten intolerant. Now that they're off gluten the boy is thriving, mum is enjoying her studies and grandma is back to being grandma - and enjoying life too. My friend's maternal gran and aunt are both seriously nutters, but refuse to get away from wheat, because they "have to have some joy in theor life." Well, when that joy is what kills your joy, maybe doing without isn't so bad - and would actually give you more joy?
ReplyDeleteThe 'sea change' of opinion on potential non-coeliac gluten sensitivity continues with an interesting editorial in the current edition of the American Journal of Gastroenterology on gluten sensitivity and IBS.
ReplyDeletehttp://www.ncbi.nlm.nih.gov/pubmed/21378766
Echoing the AAP Grand Rounds editorial a few years back on the role of food in some cases of ADHD, the effects of food on a variety of conditions is 'back of the menu'?
Emily, it's my first time on your site and i was wondering if you or any other of your blogger friends ever encounter adolescence who are " picky eaters", who have depression, mood disorders, anxiety, etc. My youngest son, 1 years old, is on Prozac and reperdone (sp?), and has never wanted to eat anything but hig carb, refined wheat products his whole life. I am convinced that there is a tie between his diet and the mood, anxiety, and depression (although there seems to be genetics as we'll as I struggle greatly with anxiety and depression but interestingly am a bodybuilder who follows a primal blueprint dirt). The discouraging part as a parent is that you just can't force your child to eat well. Is there any tips, info, etc, you can pass on for a parent like myself. Thank you - Chris
ReplyDeleteEmily, you wrote you have a "whole sheet on "nutrition for optimal mental health".
ReplyDeleteCan you send me this sheet?
It would be very grateful to me.
Thank you forward,
Attila
Hello Dr. Deans,
DeleteThis whole sheet on nutrition for optimal mental health sounds like it could benefit a lot of people. I would be interested in recieving such a sheet, but also maybe you could make it available on your blog? Or is it here somewhere and I haven't hacked well enough?
Thanks!
Not to upset anyone's apple cart but the tremendous progress we have made mentally as human beings has come while consuming this western diet and the latest genetic research demonstrates a genetic cause to Autism and schizophrenia (etc) that is actually a very valuable mutation in our thought capacities as it allows us to think without the emotional filter that clouds judgement.
ReplyDeletethe evidence appears to be sufficient enough to say wheat is a bit like smack. and does no one any good unless there is a global catastrophe because it stores well. we don't even need it evolutionarily anymore because we invented tin cans.
ReplyDeletewe seem to only need superfoods to combat this super bad one we are cultishly enslaved to.
and as for you Charlene you sound like a junky making excuses...marijuana...opium...coca...cocoa...the variance of our psychoactives is our advantage not a permanent and unending devotion to one...give us today our daily...no kindly fuck off with yournbullshit
matrix anybody? cookie anyone?
gluten Latin for glue...mmmm that bread smells lovely...that's because you area glue sniffing junki .
I so much as smell some fat bastard making fuckin cookies I want to retch... makes yuour head spin it does, if you don't notice you are under the influence.
beer...a socially acceptable ,specially brewed smack and alcohol mix.
wake up neo ya junky.