Depression and a Leaky Gut

First off, please go by and read That Paleo Guy's account of being in the middle of the latest Christchurch earthquake.  Fortunately he and his loved ones and cat are all okay.  You can also follow his twitter feed here.  I've never been at the epicenter of disaster, and I don't know that I would have acquitted myself quite so well.  I mean, once when I was in college our power was taken out by a storm, and since we lived in a crappy part of town (cheap apartment for college), it took about two weeks to get it fixed, and we congratulated ourselves on the campfire we improvised on the back porch to roast marshmallows by.  But no ground shifted.  I don't think anyone died, though quite a few trees were taken out, and there was some flooding.  Other than that, well, I've seen plenty of death and destruction in the ER and ICU, but those are more or less controlled settings.  Anyway, I hope Jamie's life is back to some sort of normalcy soon.

But for a bit of literary grounding, let's visit John Steinbeck's greatest work, East of Eden.

"But the Hebrew word, the word timshel—‘Thou mayest’— that gives a choice. It might be the most important word in the world. That says the way is open. That throws it right back on a man. For if ‘Thou mayest’—it is also true that ‘Thou mayest not."

I need a song.  Something quiet.  How about Satie's Gymnopedies No. 1? (right click in new tab)

Back to Evolutionary Psychiatry.  During the research for the Wheat and Serious Mental Illness post, I came across this intriguing paper by none other than Michael Maes, the cranky Belgian researcher who has churned out so many fascinating papers on depression and inflammation. 

Maes and crew took 51 subjects, 23 controls and 28 outpatients with Major Depressive Disorder from the outpatient clinic.  Everyone with substance abuse, anyone on medication, and anyone with chronic fatigue or other autoimmune diseases were excluded.

The basic premise of the experiment was that activation of the inflammatory response system plays a role in the pathology of major depressive disorder.  Our guts are chock full of gram negative bacteria, who have lots of a lipopolysaccharide (LPS) on their little bacterial cell membranes.  If one finds LPS in the bloodstream, that means those naughty bacteria are somehow squeezing through the so-called tight junctions of our intestinal tract - a leaky gut.  That would be bad.  And, not surprisingly, LPS found in the bloodstream ("systemic LPS") results in rapid increases in TNFalpha levels, which might remain elevated for as long as 10 months.  Brain microglia (immune cells in the brain) launch into action to fight the invasion and send out more inflammatory cytokines.  LPS in the system results in elevations of all those cytokines associated with major depressive disorder - TNFalpha, IL-6, IL1beta.  In animal studies, LPS administration results in an appearance of symptoms of poor appetite, psychomotor retardation (meaning lack of normal fidgeting movement, characteristic of depression), malaise, and loss of interest.  These symptoms are very similar to the clinical symptoms of depressive disorders. Increased LPS also seems to induce the catabolism of tryptophan (meaning more tryptophan, the amino acid precursor of serotonin, is chewed up and not used to make serotonin.)

So Maes checked antibodies (IgA and IgM - basically, gut antibodies and freshly minted antibodies) to LPS of 6 different enterobacteria.  Turns out that IgM and/or IgA were significantly elevated against most of the enterobacteria in the subjects with major depressive disorder.

In short, people with major depressive disorders were busy mounting an immune response to bacteria which never should be in the inner sanctum of the body in the first place - bacteria that live in the gut, and ought to stay in the gut.  Symptoms of irritable bowel, fatigue, and "a subjective feeling of infection" were most likely to be associated with a large immune response. 

Maes goes on to describe some interesting characteristics of the leaky gut - he contends that an inflammatory response itself actually worsens the leaky gut, that the activation of interferon gamma and IL-6 help the gram negative bacteria use the lipid rafts to get through the gut lining into the bloodstream.  That is interesting, as inflammatory response is increased in response to stress.  So stressful life events might in themselves increase the permeability of the gut.  (Jamie, do some yoga!).  Other things that induce lipopolysaccharide translocation - alcoholism, infections such as AIDS, inflammatory bowel disease (like ulcerative colitis or crohn's), and autoimmune disorders.

Maes ends his paper by optimistically suggesting that people with major depressive disorder be checked for the presence of leaky guts via measurements of IgM and IgA against LPS, and that those with leaky guts should be treated with a "leaky gut diet." (1) (the reference indicates one can write the Maes researchers to get the details of the diet - which I have done this evening!).

So - once again - don't have a leaky gut!  As Robb Wolf would say, keep your poo where it belongs.