Handel and the Biology of Allergy, Atopy, and Suicide

With respect to classical music, I'm a much bigger fan of the classical and romantic composers (Mozart, Beethoven and all those Russian guys like Rimsky-Korsakoff) than the earlier baroque composers (such as Bach and Handel).   Baroque is beautiful and often awe-inspiring, but too structured for my taste --  like a doily or a stained glass window in a church.  Back then gardens were arranged into strict geometric designs.  We caged nature.  Then pastoralism came into vogue, and we get landscape architecture that was meant to be natural and pleasing rather than quite so civilized, and the music of the time reflects this aesthetic as well.  The structure and expectations of the preceding baroque era seemed to squeeze the lyricism out of baroque music, though not the beauty.

But a baroque giant, Handel, wrote the Largo from Xerxes, a selection of music that seems to wrest poetry from rigidity.  It's an amazing piece, before its time.  A game-changer - who knew Handel could be passionate?  According to Wikipedia, Mozart said of Handel, "[He] understands affect better than any of us.  When he chooses, he strikes like a thunderbolt."  Right click to open in new tab.

We have our biology, our natures.  And yet we dare impose the structure of agriculture and pharmacology  upon it… with an incomplete understanding, at best, particularly in the brain.  Such incomplete understanding will lead seemingly learned folks to suggest that we are all diabetic.  (We are not).  And that glucose is not a toxin but foods that raise blood sugar levels are toxic (er, what?).  I probably should not stick my foot into this one, as I am not a metabolism blogger, but for heaven's sake.  Without glucose in the bloodstream we are dead.  With too much glucose we are poisoned.

Physiology is all about Goldilocks, the right amounts, and the case that all starches are toxic for the vast majority of people is a very, very poor one.  And if fasting glucose and overall levels of circulating glucose are important, the strict low-carber who cheats every once in a while might be in more trouble than the healthy starchy-carb eater who will be more exquisitely insulin-sensitive.  As Kurt Harris and Melissa McEwen have noted, there is no evolutionary precedent for lifelong very low carb diets, and plenty of examples of healthy cultures who eat starchy carbs.  So with our incomplete understanding of physiology, I feel it is a safer bet to use reasonable precedent rather than a zero-carb theory of an optimal longevity diet as a prescription for most people.  Certainly there are likely exceptions - seizures, dementia, the first stage of weight loss, in many folks with diabetes.  Personally I think calling starch a poison for the majority of people makes about as much sense as demonizing saturated fat.

So.  Back to allergies and suicide.  This part of the post is for me, really.  I need a spot to look back and see the nitty gritty stuff organized in a way that makes sense to me.  Actually, this is the point of the entire blog.  My self-taught fellowship in Evolutionary Psychiatry.

In the beginning, there were Th1 and Th2 helper cells.  These are soldiers of our immune system, called lymphocytes, with different capabilities and called into action in different circumstances.  The call to war comes in the form of the release of inflammatory cytokines.  There are a whole soup of these chemosignals, released also primarily by T lymphocytes, mostly named interleukins, which are shortened to IL-1, IL-2, IL-3, etc. etc.

In general - the release of inflammatory cytokines can lead to reduced activities and social interaction,  and it can activate the HPA axis which can lead to supernormal responses to stress, which can further ramp up the inflammatory response.  Elevated pro-inflammatory cytokines can activate the IDO enzyme, reducing serotonin production (this may explain the link between allergy and suicide).  Certain types of Th2 related cytokines also increase insomnia.  Allergy, then, does not increase the risk of suicide by making people feel sick, but directly through inflammatory means, leading to people withdrawing from social activities and over-react to stressful situations.

What are some more specific features?  Well, proinflammatory cytokines released at the time of the allergic reaction activate the HPA axis - the glucocorticoids and catecholamines cause a suppression of Th1 and a shift to Th2 activity by inhibiting IL-12 and promoting IL-10.  The pro-inflammatory cytokines also cause dysfunction of corticosteroid receptors.  The Th2 lymphocyte produces IL-4, which can effect serotonin metabolism as well - and IL-4 is known to have more effect in people with some genes than others.

En anglais, we are talking here a direct mechanism by which a certain kind of stress, allergy, can affect the neurochemicals in the brain and therefore behavior, and it seems that some people are genetically more vulnerable to this stress than others.  That said, other researchers have postulated that the Th1 cytokines impair the serotonin machinery even more than the Th2 ones… we're back to not too hot, not too cold, not too soft, not too hard.  It all has to be just right.  And what is just right?  Depends on your genes and your epigenetics.  Superimposing an emulation of the evolutionary milieu is only a first approximation and a good guess.