Of Mice, Medicine, and Malefactors

Older Brother and his wife, Aunt Krusty, sent me a fabulous little doohicky from a medieval town they visited. It’s a brooch of a common design element used in the Middle Ages: a tabby cat with two tails and fabulous eyebrows offering a mouse, with the legend, “visis mu” — “here’s the mouse.”

Pewter pin of tabby cat as described in text.

Close inspection shows both letter “s”s to be upside down. I’ve known a few artisans, and they like making people twist their heads around. Besides, that’s relevant. You’ll see why.

The enclosed card contains the usual wonderfully vague, semi-academic wording saying that animals with two tails (no mention of fabulous eyebrows) are signifiers of evil forces at work, but beyond that, nobody really knows what this means.

I thought some academics kept cats…?

My lovely polyglot friend Sylvie does. Sylvie is a CRPS compatriot who lost a frightening percentage of weight late last year, from which she’s still recovering. Her cat Nala has become a serial killer of the entire species Rodentia, bringing her grisly accomplishments to lay at Sylvie’s feet — or couch, or pillow — with startling frequency. Naturally, they aren’t always quite dead.

Pinto cat biting into white mouse on a lawn.

Not Nala, but a kindred spirit. Photo Tomasz Sienicki @ Wikimedia Commons.


Cats don’t have thumbs, so they don’t really get it about cooking and cupboards. All Nala knows is that Sylvie obviously needs to work on her hunting skills, but in the meantime, Nala can at least help her fatten up.

Also, cats tend to gatomorphize, just as those of us who are close to them tend to anthropomorphize. Nala has no idea that mice, gophers, shrews, and moles do Sylvie no good at all; that, on the contrary, they’re upsetting, messy, and potentially infectious. Nala thinks they’re good, and Nala cares for Sylvie, so they must be good for Sylvie.

She honestly believes that, with all her furry, loving little heart. “Visis mu! Have this great mouse!” So the slaughter continues.

Sylvie’s garden blooms, but her house is an abattoir at times. This is not a bad metaphor for explaining one of the more difficult aspects of being under a doctor’s care.

Most doctors really mean well. Becoming a physician takes an enormous amount of work, which requires great commitment to complete. It’s a hard job with ridiculous hours, especially for the first few years.

That doesn’t mean they’re all bright or gifted or even humane. It just means they believe in the value of medicine and surgery, enough to spend a decade or more learning to do it.

Line drawing of doctor going over an x-ray with patients.

There is much care and dedication among many doctors.


Doctors are intensely, let’s say, socialized to stay within the parameters of accepted practice. It keeps them out of trouble, although it may also keep them from true excellence at times.

Mostly, they love those parameters. They love having guidelines. They are truly, madly, deeply convinced of the value of the meds and procedures that they’re trained in. It doesn’t help that, if they put a foot wrong outside of those parameters and things don’t go well, they can lose everything. They are heavily incented, so to speak, to stay inside whatever they understand their parameters to be.

And, of course, the peer pressure is enormous.

And, of course, the peer pressure is enormous.


Now, this is tough for CRPS patients. There is so much variation from one CRPSer to the next, that there are NO established treatment parameters that meet the medical gold standard of being consistent, repeatable and reliable over a majority of patients.

None. Nada. Zilch. There is not one thing that consistently works well for most of us — at least nothing that comes from a bottle or an operating room. Activity, rest, hydration and nutrition all seem to be key, but even their benefits are hugely variable, and you rarely hear about them from physicians.

For a while, it was thought that COX-2 inhibitors combined with membrane stabilizers, came close to being a semi-magical bullet. (Gabapentin/ Neurontin, pregabalin/Lyrica, and so on, are known to most patients as anti-seizure meds, but many healthcare providers call them membrane stabilizers.)

Then it turned out that the Dr. Scott Reuben, the physician who popularized that treatment, was making the numbers up (here, reported to his colleagues and here, reported to science fans.)

Old poster of a show called, "Pinocchio, the tale of a marionette"

He was so busy being a puppet of the drug companies paying him, that he forgot what it means to be real.


COX-2 inhibitors were given a general thumbs-down over cardiac effects (which many people with chronic CRPS have enough trouble with anyway) and, as peri-surgical meds, did not live up to Reuben’s promise that subsequent chronic pain would be less.

Ironically, it had already been established that 500 mg of vitamin C two or three times daily for 3 months after surgery does have significant demonstrated benefit, reducing the incidence of CRPS – the most intractable and severe form of chronic pain – by 35-80%, depending on the extremity, extent of injury, and probably the degree of compliance. Moreover, vitamin C is very cheap, as well as very effective. (See extensive links list below.)

The anti-seizure meds, unfortunately for pain patients, did not get removed from first-line treatment.

By then, unfortunately, whole nations (Great Britain and the Netherlands, take a bow) had adopted Reuben’s corrupt recommendations for first-line treatment. It takes a lot more effort to undo that level of adoption than it does to hoodwink an entire sub-economy of peer reviewers and medical specialists, apparently.

The arrogantly reputable journals that accepted his work, and subsequently published other work which was based unquestioningly on his false results, are still trying to live it down. What’s interesting is that other doctors couldn’t replicate his results, so he was the only one publishing these great data… yet journals and physicians continued to publish and follow his recommendations. I do hope the journals revised their “peer-review” process to include more actual, I don’t know, reviewing, perhaps by peers.

Old cartoon of Pinocchio sitting on a pile of books, with a book open on his lap.

It took a lot of people to permit and perpetuate Reuben’s false reports. They are not innocent.


It could take decades to undo much of his damage, and meanwhile, the advancement of treatment has been down the wrong track for years, while other more appropriate avenues of treatment have been ignored or even forgotten.

So, millions of CRPS patients are being first-lined with truly obnoxious meds with iffy benefits and ghastly side-effects, rather than being examined as individuals, and assessed as to whether:

  • neurotransmitter support, most provably with antidepressants, would be more appropriate, given disease-related onset of affective symptoms (antidepressants), sleep problems (tricyclics), or dysautonomia (SNRI);
  • a short, hard attack of narcotics and aggressive PT would answer in the case of a hardy, active, or young person;
  • a proprietary or tech-based treatment, like TCMI or Calmare, are indicated for those who show active neuroplasticity or respond well to electrical stim; or
  • this person is a good candidate for ketamine protocols of one kind or another, some of which are no more toxic than membrane stabilizers.
  • it might be reasonable to try a more experimental approach which has demonstrated significant promise, notably magnesium infusions, immune globulin therapy, or temporary immune suppression.

Oops… Doctors, as a group, forgot to look at the patients in their excitement to have a designated treatment protocol. “Visis mu! Take this mouse – it’s government approved!

If you've worked with government agencies, you know why they're laughing.

If you’ve worked with government agencies, you know why they’re laughing.


But the doctors doing the offering really think this is a great idea. That’s what the guidelines say, after all, and they are evidence-based – except that that evidence was cooked.

While anti-seizure meds do work very well for some, starting with them reflexively is not reasonable: the cost-benefit profile is worse than most of the other potential first-line alternatives, due to high rates of side effects and comparatively unimpressive rates of usefulness.

Using them as a first-line treatment delays more effective, lower-cost treatment for many people in horrific pain, and, between the delay and the cognitive and neurologic side effects of this class of drugs, causes greater impairment (with higher associated costs) in far too many. It should be a second or even third line treatment, if you go by the evidence that has remained credible – taking a back seat to less fraught (not perfect, but still less problematic) therapeutic agents and interventions.

But the docs who lean on it really think it’s great.

sketch of excessively happy doctor running with a hypodermic needle

“Visis mu! Visis mu! Look – it’s a great mouse!”


Reminds me of my previous pain doctor, a competent technician with a bedside manner directly related to the patient’s appearance. He has a good reputation in his area – which tells you what a lot of rubbishy practitioners there were in the area.

He wanted to shove into the neck of my spinal column a couple of widgets which were the size of Starbucks drinking straws – you know, those really fat ones that you could suck a steak through, if it’s tender enough. Two of those, jammed into a six-inch length of a space that didn’t have enough room for one, and which – as we now know – was already inflamed in much the same way that the spinal cord of someone with a spinal cord injury is inflamed.

He liked it because shoving surgical hardware into other people’s bodies is what he does best, and these widgets have embedded electrodes which could zap the pain signal at the spinal root of my arms and he thought it would work really well and I had the right psych profile for it and this was the greatest thing since sliced bread.

"Visis mu! Visis mu! This is a truly excellent mouse which I am shoving smugly up your spine!"

“Visis mu! Visis mu! This is a truly excellent mouse which I am shoving smugly up your spine!”


It was a nice idea, and, again, this particular thing works spectacularly well for some people. For me, not so much. In fact, it was a disaster. It was truly worse than the CRPS pain, which takes some doing. The equipment trial still gives me spasms due to the mere memory of the staggering physical trauma it entailed.

Truly, each of us is unique.

Once he realized that I couldn’t accept his mouse, his whole manner changed. Just like a sulky cat, nursing his disappointment seemed a lot more important to him than finding something that would help me.

How could I be so callow and blind that I couldn’t appreciate this great mouse he wanted to give me? There’s just no helping some people! His neglect and disaffection was so damaging I had to fire him and move on to the excellent Dr. Richeimer at USC Pain Center, 4 hours’ drive away and worth the two-night stay in the armpit of LA.

Another dear friend, the angelically kind M, has roughly 3 dozen anaphylactic reactions a year. She is so hyper-reactive to so many things that driving past a town with the wind in the wrong direction could be the death of her. 3 dozen anaphylactic reactions a year, and she’s in her fifties now. Yes, amazing.

She saw a young cardiologist, who did what young cardiologists do: he threw upon her a huge, bloody gopher, covered in prickles and gore. “Your heart is dicky! This could kill you in a year! Visis mu, I can save you! Isn’t this exciting?”

Sepia-toned photo of a very dead, gutted gopher.

I processed this image out of respect for M’s exquisite sensibilities.


Personally, I think the appropriate thing to do is to pick that gopher up and shove it down his throat, but when a patient does it, it’s assault and battery with a biohazardous weapon.

The cardiologist, naturally, is doing exactly what he was trained to do and is wildly excited to have such a thrilling case and such interesting news. She, who already faces death on a weekly basis, should clearly get wound up about this because it might kill her if she doesn’t.

Gopher poking head out of hole, looking grumpy, with long claws and nasty teeth.

“Visis mu! This is a glorious mou — er, gopher! Check out those charming teeth, those tiny claws, that helpful expression! Awesome!

A brickbat? A muzzle? What do you think? Words simply fail. All I can think of is applying to him the kind of cat that has nine tails. It’s not a good way to model compassion, let alone tact, however.

As for me, I have to pick a primary doc for myself. My old one retired from private practice, and I miss him, because I could just walk in and look at him and he’d know.

I’m just thrilled at the prospect of training someone new, who will be a generalist treating the peripheral issues of someone with an incredibly peripheral-intensive disease. There will to be many rounds of “visis mu”, as he comes up to speed. And, since it’s all well-intended, I have to find a way to accept one or two mice as graciously as possible. One can only recoil so often before they decide they can’t treat you.

"Visis mu! I care for you, so let me do this wildly inappropriate thing, because I’m too rushed to think things all the way through!"

“Visis mu! I care for you, so let me do this wildly inappropriate thing, because I’m too rushed to think things all the way through!”


They mean well. They really do.

I never have figured out what to do when a cat, with every evidence of caring attention, brings me a mouse. I try to be nice about it, and that’s the best I can do.

Obit
Sadly, Sylvie’s furry little caregiver, Nala, departed this earth for the Happy Hunting Grounds. By a series of flukes, Sylvie wound up with a rescue cat, Filou (meaning roughly “brat” or “mischief-maker”), who has taken over her care with great enthusiasm — and much less bloodshed.

Links

Grouped by subject.

Sylvie’s blog on “neuroalgodystrophie”, mostly French but some bilingual French/English: http://sylvieghyselscrpsdrc.wordpress.com/

Blog on managing immune suppression and chronic pain with few drugs and much natural care (not M’s, but in that field): http://www.tamingthebeast.ca/

Scott Reuben’s villainy, as reported to colleagues in Anesthesiology News:
http://www.anesthesiologynews.com/ViewArticle.aspx?d_id=21&a_id=12868
And in Scientific American: http://www.scientificamerican.com/article/a-medical-madoff-anesthestesiologist-faked-data/

Vitamin C after surgery or trauma, value established before Reuben’s fall:
From 1999, in The Lancet: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(99)03059-7/abstract
From 2002, in Belgian orthopedic periodical: http://www.ncbi.nlm.nih.gov/pubmed/12584978
From 2007, in the Journal of Bone and Joint Surgery: http://jbjs.org/content/89/7/1424.long

CRPS at the top of the McGill Pain Index:
https://elleandtheautognome.wordpress.com/2012/09/05/mcgill-pain-index-crps-and-fibromyalgia/

UK treatment protocols for GPs treating CRPS: https://www.rcplondon.ac.uk/sites/default/files/documents/complex-regional-pain-full-guideline.pdf

Netherlands treatment protocols for treating CRPS: http://www.posttraumatischedystrofie.nl/pdf/CRPS_I_Guidelines_patient_version.pdf

Relatively useful treatments for CRPS:
Most suggestions are pulled from the current IASP recommendations for diagnosis and treatment of CRPS or the pivotal work of Dr. R. J. Schwartzman, Dr. van Rijn, and Dr. Breuhl (part of the team that developed the IASP guidelines), with updates from recent science available on PubMed.

Dr. Robert J. Schwartzman’s seminal works..
Outstanding primer on CRPS and what it can do in Systemic Complications of Complex Regional Pain Syndrome
Neuropsychological deficits associated with Complex Regional Pain Syndrome

Dr. van Rijn’s Spreading of complex regional pain syndrome: not a random process

IASP current recommendations: http://onlinelibrary.wiley.com/doi/10.1111/pme.12033/full#pme12033-sec-0023
Simplified diagnostic tool using IASP criteria: http://biowizardry.info/wp/2014/12/the-hidden-simplicity-of-diagnosing-complex-regional-pain-syndrome/

The authors have their blind spots and biases, of course, so researching any therapies that sound interesting is a good use of time.

The National Library of Medicine at the National Institutes of Health (U.S.) is an outstanding clearinghouse of articles from peer-reviewed scientific journals: http://www.ncbi.nlm.nih.gov/pubmed/?term=complex+regional+pain+syndrome
Just add the term of the treatment you’re interested in to the MeSH term, “complex regional pain syndrome”, to maximize useful hits.

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CRPS, ANS dysfunction, and chronic vertigo

The central nervous system is bathed in fluid. This fluid provides a buffer against shock, as well as providing a good medium for the transmission of chemical signals. (Electrical signals are handled by the neurons.) The central nervous system is extremely sensitive to dehydration, which is why headaches are so common: most people are somewhat dehydrated. We consider ourselves too busy to drink water and whizz it out again.

Water is also the main ingredient of blood and lymph. These two essential fluids bring nutrition to the cells, transport chemical signals such as hormones and regulatory signals, and carry away cellular garbage. When there’s not enough of them, that doesn’t happen very well. More garbage piles up in the tissues, aging happens faster, disease trends faster, our muscles get stiffer, it’s harder to recuperate from injuries and illnesses, our sex lives suffer, and we just don’t feel as good.

With that in mind, not having the time to drink in water, process it through, and whizz it out again doesn’t really make sense, but a lot of us are really attached to that idea.

Reality checks

One of the really ducky things about diseases like CRPS, especially when there is strong autonomic involvement, is that normal quantities of fluids (and vitamins, proteins, and other nutrients) are often inadequate to our unusual metabolic needs. It may be possible for a basically healthy person to meet all their needs with three good meals and three or four liters of water per day, but for systems so consistently under siege as those with CRPS, it may be impossible to meet metabolic needs within these (otherwise very reasonable) parameters.

I have several friends with terrible vertigo, due to autonomic dysfunction in CRPS. This isn’t the, “I held my breath too long,” kind of dizziness. This is the kind of dizziness where you can’t keep your feet under you, you feel like you’re going to throw up, and it JUST WON’T QUIT.

The mechanism behind this has only been researched recently. It’s not very well understood. I’m hoping for an informative comment from an expert on this…

What’s happening (partly) is that the vessels, which are directed by the autonomic nervous system, are flopping open too much. This means that the normal amount of fluid in the blood, lymph, and cerebrospinal fluid has to fill a space that’s considerably larger than normal. What you get is a type of hypovolemic shock, where the brain and major organs simply can’t get enough nutrition, oxygen, and garbage collection.

This normally happens on a short-term basis, after some assault on the system; normally, it’s either corrected quickly, or the person dies.

There are very few instances where this happens continuously over time, but with CRPS, some people have to live with it. It can make doing anything impossible, and if you try to imagine, just for 5 minutes, what it’s like to be that desperately dizzy and try to do anything — even get a fork to your mouth without bloodshed — you’ll see what I mean.

Sometimes, these symptoms can be somewhat reduced. There are pharmaceutical and mechanical approaches, each with its drawbacks and benefits. Since doctors (and many patients) tend to think in terms of pharmaceuticals first, let’s start there.

Pharmaceutical management

Whenever you think in terms of disease and pharmaceuticals, it’s important to keep in mind that:

  • Every system is unique.
  • Every system with CRPS is even stranger.
  • Unless you’re a doctor getting a visit from a pharmaceutical rep, there is no such thing as a free lunch. Everything you take in affects your whole system. With our systems under siege, it behooves us to be mindful of our chemistry.

NB: This is not intended to diagnose, treat, or cure any disease. Consult your physician with any questions, and if your doctor can’t give you a credible answer, get a referral to someone who might be able to.

Vasopressors, which can help restrict blood vessel size, have mixed results. They depend on the regulatory system being able to work somewhat, which is problematic in CRPS. Moreover, they have their own side effects, and given what a cocktail of medications most people with CRPS are on anyway, this can be quite noticeable. It has to be handled on a case-by-case basis.

Anti-dizziness pills, such as Atarax, affect the central nervous system and tend to make people sleepy and goofy. They are related to antihistamines and acid-suppressing medications (H2 inhibitors), and for those with hotwired immune systems and the nutrient assimilation problems common in chronic CRPS, they’re not without side effects. Moreover, because they address only the generic mechanism for dizziness, but not the particular mechanism for CRPS/ANS vertigo, they don’t necessarily help in these cases. Also, case-by-case basis.

Some SSRIs, typically used as antidepressants but extremely effective for nerve pain, can also provide support for the ANS. There is additional benefit to the use of SSRIs, because of their assistance with the nerve pain component of CRPS; when they can also improve the autonomic nervous system, it’s a big deal. Naturally, SSRIs being the idiosyncratic category that they are, it can take a few tries to find the one that works best in each person’s system. As I learned the hard way, getting the dose right can be a long and interesting task, given the idiosyncratic nature of our systems.

Mechanical management

Mechanically, it’s possible to increase blood volume by taking in lots of fluids, even if you already drink “enough.” “Enough” is a relative term, and what’s “enough” for a person with a normal autonomic nervous system may be “completely inadequate” for somebody with vertigo due to CRPS.

Blood pressure is a complex system, involving more than just fluid, vessels and the brain. Maintaining electrolytes helps contribute to a healthier fluid balance, and towards that end, sometimes doctors suggest increasing your salt intake. That only raises your blood pressure when you already have a predisposition to high blood pressure, so it may not be obviously useful; however, adequate sodium is important in maintaining renal function and supporting potassium levels.

Potassium is another key electrolyte, along with magnesium (found in Epsom salt), calcium, and bicarbonate. It doesn’t take much; four or five of the smallest grains of Epsom salt, stirred into a glass of water, can make a noticeable difference when you are magnesium depleted. Also, it usually makes the water taste better.

It’s easy to tell when you’ve taken too much, partly because it doesn’t taste good, but especially when it gives you the runs. Less is generally better than more!

Bicarbonate is better managed by eating plenty of vegetables, rather than trying to supplement and get the dose just right. Having an overly alkaline system doesn’t feel very good, either.

Calcium and magnesium are present in food, especially if you’re eating plenty of nuts and leafy greens. If you have CRPS, you really want to eat plenty of nuts and leafy greens! They provide so much in the way of A and B vitamins, antioxidants, minerals (which support cellular processes and regulation), healthy fats (which help your body absorb your nutrients and protect your nerves), fiber, digestible protein (which helps your body absorb the calcium), and so much else of what your body really needs.

Activity, even horizontal activity, even just stretching out gently in bed, provides the body with much needed prompting about how to keep things moving. It keeps your muscles loose, so that your body is more comfortable to live in; it also activates sensors in your joints which communicate with your body’s regulatory mechanisms, and this helps with maintaining blood pressure (one can only hope it helps enough.)

Any movement is better than no movement.

Changes in position should happen slowly, which is terribly frustrating, but it’s going to take as long as it takes. If your body doesn’t get to move, it forgets how to handle itself in movement. This becomes a negative feedback loop.

So, keep moving, even if you’re not moving in any way that the doctor would recognize. Frankly, most doctors are somewhat limited in their ideas of what constitutes exercise. Most of them have no trouble walking from the car to the office, let alone from the bedroom to the kitchen.

Don’t let perfection assassinate your drive towards improvement. Do what you can, and don’t sweat the rest.

  • If you can’t run around the park, walk around the block;
  • If you can’t walk around the block, practice ballet or t’ai chi with one hand on the back of the sofa;
  • If you can’t do that, fire up YouTube and do chair qi gong or chair yoga;
  • If you can’t do that, stretch out gently in bed, and do range of motion exercises. (This is a wonderfully pretentious term for moving each limb all the way up, then all the way down; all the way in, then all the way out.)

There is always something you can do to keep your joints active.

Moving your joints sends a message to your regulatory centers that they need to pay a little more attention to your blood pressure. That’s why it’s important to stay active. Our regulatory systems are screwed up enough; we need to keep them gently tuned, and be persistent about it, even when it seems absurd to do so. The habit of activity will serve you well for the rest of your life.

I’m aware that there are some herbs that have tonic effects on blood pressure and possibly the ANS. I would love to learn more about that.

Assume there is a future, and that what you do, even little things, can change how it goes.

That’s a good general policy, anyway. Especially with CRPS.

While I’ve known all this for many years, applying it to CRPS has been an education. When I’m able to focus a little longer, I’ll put together some references. Meanwhile, any of you who have references, either to support or contradict any of this, would be very welcome to post them in the comments.

I look forward to better science and better medicine for chronic vertigo in CRPS. It’s so thoroughly disabling, yet so thoroughly underrated.

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Repeated stress knocks out the prefrontal cortex

… In a number of ways.
This article describes a new finding which relates memory loss and cognitive dysfunction to a loss of glutamate receptors in the prefrontal cortex (PFC):
body=http%3A%2F%2Fwww.sciencedaily.com%2Freleases%2F2012%2F03%2F120307132202.htm&subject=How+repeated+stress+impairs+memory
They state that this is why the PFC tends to falter in the face of repeated stress: the receptors for one of the key neurotransmitters become depopulated, leaving fewer sites to accept the glutamate and allow that part of the brain to do its job.
Cognitive impairment in the face of repeated or chronic stress is not a monolithic problem, though. Memory and decision-making are probably the most complex of brain tasks, and there are plenty of things that go wrong when memory and cognition fail.
Other factors include dopamine depletion, leaving less of that transmitter to carry messages back from the PFC, thereby making executive decisions harder to make and still harder to follow through on. (I wrote a previous post on dopamine and decision making. I’ll dig it up and link over.)
And then there’s the adrenaline overproduction and overuse that characterizes chronic and repeated stress, leading to disruption of the hypothalamic-pituitary-adrenal axis (the body’s entire signaling structure for body processes) which contributes to brain dysfunction in still more ways: by disrupting sleep, which disrupts memory formation and impedes logic; and by contributing to the rise of metabolic syndrome, creating less stable blood sugar — which, in the brain, adds considerable insult to injury: a hungry brain is a low-functioning brain.
Take your vacations. Simplify your life. Move your body around regularly. Meditate early and often. If you cherish your brain, you might as well let it work — and that means getting a half-Nelson on stress before it gets one on you.

Links:
The article on overuse of dopamine (on my Living Anyway blog): http://livinganyway.blogspot.com/2011/03/dopamine-poverty-and-pain-lighter-side.html
Another Biowizardry entry on neurotransmitters: http://biowizardry.blogspot.com/2011/08/scared-of-wrong-things-role-of-mao-in.html

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Scared of the wrong things: depressive chemistry and danger

Funny how the whole delicate neurological/neurochemical structure is so interwoven:

“…The researchers suggest that the strange defensive behavior exhibited by the enzyme-deficient mice may actually reflect a limited range of adaptive responses and lack of emotional flexibility — the mice may only have one gear for fear.”

We’ve all known people who make exaggerated choices around danger that make no sense to ourselves. (Having heard my mother and my sometime partner on the subject of my riding motorcycles, I’m pretty sure of that.) However, only at my most desperately depressed have I engaged in unsafe sex, which is the second stupidest risk I can think of (the first having nothing to do with motorcycles.) 
The role of MAO-A and depressive neurotransmitters, combined with the dopamine-deficient sense of hopelessness and diminished executive function, make that make sense: 
Monoamine oxidase A is the main enzyme in the brain that breaks down serotonin, norepinephrine and dopamine…”
Which makes me think that it’s possible, in humans in vivo, to be deficient in both MAO-A and in dopamine, serotonin, etc. It would explain a lot about certain mental states, even though it seems chemically tautological at first glance to be both Big 3-deficient and MAO-A deficient. As I’ve learned, though, deficiency and dysregulation do have additive effects, they don’t cancel each other out. 
I’d like to see more studies which monitor serum and brain levels of these key chemicals together, preferably in humans. Science tends to take the simplest possible approach, which is rarely the most realistic and not necessarily the most telling. It does get funded and it does make it simpler to design the studies. 

I look forward to having more sophisticated thinkers (and funders) get into this branch of psychoneurology, since all these lively lovely tiny bits of info won’t come together in a meaningful way until we can look at them in concert with a higher degree of exactitude and completeness. I suppose I’ll have to be patient. And careful. 
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News flash: the gut and brain are connected!

The obvious scatological humor will be left alone. Guys, you know what I mean. (Girls who were outnumbered by your brothers, you too.)

I started to blog this article because the forehead-smacking tone of the revelation that the gut might relate to the brain was a bit too much for me. On closer examination, it looks like the misplaced drama is the writer’s, not the scientists’.

One of the places where serotonin is released is in the gut, where it helps digest proteins. That’s the most obvious “duh” moment here. Moreover, as those of us who remember our embryology know, the inter-relationships and constant correspondence between neurology and gut, gut and immunity, immunity and endocrine system, endocrine and neurological system are all too intense and interlocked for words.

Most studies make brutally clear that these so-called systems are medically treated as separate and distinct, but our bodies never got that memo. It’s all the same system, as far as the body is concerned.

Much of this researcher’s recent work focuses on neurology of the gut — enteric neurology. It’s a real thing now. His prior work focused on the biological environment in the gut, or the intestinal microbiota.

// START Word geek goes wild:
Sometimes, I just love medical terminology for the way it rolls, hops, and bounces off the tongue. Enteric neurology. Intestinal microbiota. Hypothalamic-pituitary-adrenal axis.

Maybe that last one doesn’t work so well.
// END Word geeking.

If you can stand the medical and chemical jargon, it’s worth looking into some of his work. It’s probably not a stretch to call it prescient, in that it is likely to lay the foundations for our emerging understanding of the gut as a more complex and self-managing, yet interlocked, set of systems than we’ve ever imagined before.

I can’t find the original science article, just this unsatisfactory and superficial overview. It says that intestinal microbiota affect the person’s mood and feelings, and that it’s possible to deliver specific probiotics (like yogurt species, naturally-fermented cole slaw, certain cheeses and the like) in order to have a specific benefit to the neurological system.

If you were an empiricist, like me, it would sound like “eating good, living food leads to better mental health,” which healers have been saying for millenia. But far be it from me to steal such well-researched thunder.

Link list:

Science Daily article:
A Gut-Full of Probiotics for Your Neurological Well-Being

Credentials of lead researcher, Prof. Lyte:
Mark Lyte, Ph.D., M.S., MT (ASCP)

Wikipedia’s digest (sic) of the enteric nervous system (this seems basically congruent with the uber-geeky medical studies I looked at on the subject, so I accept it as a decent primer):
Enteric Nervous System

Couldn’t find a good overview that didn’t involve more dead rodents than I could, er, stomach.

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Hemingway: How courage and depression go together

This article is well-intended, but egregiously judgmental and woefully ignorant:

http://www.npr.org/2011/07/02/137540700/after-50-years-remembering-hemingways-farewell

If it weren’t for the inane babble puzzling over why Hemingway lived so intensely, this line would be the Winner of The Most Fatuous Statement award: 
“…in January 1961 he told his wife, Mary, that he could no longer write a single good sentence. And Hemingway would only settle for great ones.”
It wasn’t a question of settling for less than great, it was a question of how important it is to fulfill your purpose and dig some meaning out of life, even amid the unbearable. That purpose and meaning was taken from him, under the mistaken guise of treatment. 
Hemingway got electroshock therapy for his depression; a common side effect is to knock out your language abilities and cognition, sometimes for months and sometimes forever. The one thing that made his life endurable — writing like himself — was taken from him. 
Depressed people have more courage and determination than their non-depressed cohorts. Studies are finally being funded that verify this (which I’ll dig up later. Feel free to nudge me with a comment.) 
Think about that next time you curl your lip over suicide. It’s not about courage. It’s about unbearable pain and a degree of mental crippling that puts a valid life out of reach. 

Waiting and working at it until things improve is a reasonable thing to do: Hemingway waited and worked at it for  40 years, though with so little real hope for treatment. Talk about courage! It’s unthinkable how much courage he brought to bear on his life. His intensity and wild behavior were directly related to making his life bearable — and his work more compelling. Check his quoted remarks on that subject. What’s between the lines is breathtaking. 


The article’s remark about suicidal lineage is true, but poorly understood. A suicide in the family has the powerful effect of making suicide less unthinkable. There is often a genetic tweak associated with it, but that’s not all there is. The thing to know now is, we are not our predecessors; we can do more. Far more. 
Hemingway died before we developed SSRIs, SNRIs, and a tremendously improved understanding of neurochemistry, behavior, nutrition and psychodynamics. We have more options now. Lots more. Waiting and working at it is a real success path now. 
Be good to your depressed friends. You probably have no idea what they’re capable of, when they can be well again. Help them persist. 
It’s the most important thing to do: persist. A valid and bearable life is a reasonable thing to hold out for. Only death bars the door to healing. Things will change. 
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Digestive problems early in life may increase risk for depression, study suggests

http://www.sciencedaily.com/releases/2011/05/110512171517.htm?utm_source=feedburner&utm_medium=email&utm_campaign=Feed%3A+sciencedaily%2Fmind_brain+%28ScienceDaily%3A+Mind+%26+Brain+News%29

This article states that gut disturbance in early infancy/lifelong gut disturbance (the language is kinda sloppy) can trigger lifelong depression and anxiety.

This doesn’t surprise me, but most of the rest of the article does.

The rat-botherers who did the study presume it’s all about the vagus nerve. Recently, a deliciously expensive procedure which stimulates the vagus has been found to alleviate some depression. It’s good to know that.

It’s good to keep a couple other things firmly in mind first, though:

- Serotonin is produced in the small intestine, as well as the brain. It helps to digest protein. It also plays a role in immune signaling. Think that could possibly be related, either to depression or to inflamed gut syndromes? H’mmm…

- My first thought: get right on top of infant digestive problems. That means getting serious about both prevention and cure.

Oddly, that idea wasn’t even mentioned, even though prevention is infinitely better than trying to manage a lifelong downer like IBS or depression — let alone both!

Prevention is simple in concept, but inexcusably difficult in our current system. With babies, it’s easy: get dead-serious about breastfeeding. Where that’s not possible, put aside formulas at the first sign of allergy. Don’t switch between cow and soy milk, two of the most allergenic infant proteins on the planet; milk more goats and camels. Go to a breastmilk-bank. Find your local midwives because they are much better with the idea that birth is only the beginning of a much longer life, and they should know how to figure this out. If they don’t, they can tell you who else to call.

And punctual treatment for troublesome insides — with the least invasive meds. Interfere with their little regulatory systems as little as possible, but take care of the problem. For indigestion, chamomile and calcium carbonate are much better than h2-inhibitors (Zantac, Prilosec and the like.) Chamomile also soothes the mind and settles the emotions, so the kid can relax.

Try elimination diets to screen for allergies. Sadly, wheat, eggs, cow dairy, soy, and corn are common allergens which affect the developing gut — and the developing skin and brain, because their little bodies never got the memo that all of these systems are supposed to be separate from each other.

Google those terms, discuss them with your midwife/pediatrician/nurse practitioner, and take care of the problem at its source.

You don’t want more depressed people in the world. There are better things to do with infants than let their guts screw up a good life, handing them into the craps-shooting care of multiple pharmaceuticals and invasive procedures.

When I get on the CPU, I’ll set up more links for my factual statements. This is it from the iPhone.

Bon appetit!

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Picking a target (volunteers welcome)

I have several topics competing for attention:

- The lowdown on neurotransmitters: what they are, what they do, where and how they’re made.
I can’t find my old version, but I’d rather rewrite it anyway and lard it heavily with current references and links.

- After that, there’s more to say about how neurotransmitters can be affected — for better or worse — by what you do, what you eat, and how you use your noggin.
This is aimed at that helpless feeling we tend to get when our minds go awry. There’s a lot you can do to mend your mind from the inside out, either with med help or without. I’d like to put the main strategies together here, because so much advice seems conflicting. Mostly, it isn’t, but it would be good to see why.

- Putting the “might” back in mitochondria: how to support your mitochondria in sickness and protect them in health.
This goes into the mechanics and physiology of the reparative stuff I mentioned in the prior article on mitochondria.

These are the big 3. Any preferences?

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