Further Evidence that Mental Illness Exists

Long, long, long ago, I wrote several posts that were later updated for Psychology Today, mostly because it is the basis for my understanding of the pathology of depression with regards to that Big Bad of Diseases of Civilization, inflammation.  A nice tie-in to all those posts is here:

Depression Crashed Your Party

It is not, perhaps the friendliest of posts with all that biochemistry and all.  But rest assured it is of vital importance.  Especially this diagram (right click to open in new page and take a look).   And this post will not be particularly friendly either.  Mostly because I have caught up on a recent skirmish in the war between medicine and psychiatry, begun by the book reviews by the former editor and chief of The New England Journal of Medicine, Dr. Marcia Angell, and all the big names in psychiatry writers, specifically an article in Psychiatric Times by Ronald Pies, M.D. "Misunderstanding Psychiatry (and Philosophy) at the Highest Level."

In case you do not happen to be a clinical psychiatrist and do not care to dive into the debate, let me paraphrase (and allow me to take extreme liberty with my own interpretation of the stance of the two sides):  Dr. Angell:  "Psychiatrists are witch doctors."  Psychiatrists:  "You are ignorant and misinformed."

Music - Danse Diabolique (right click to open in new tab)

It is hard to be misunderstood.  Rest assured that I do not rely on incantations to treat my patients, but I do dislike equating psychiatry with the DSMIV.  The DSMIV, the cookbook describing all the diagnoses for research and insurance billing purposes, is not psychiatry.  A good psychiatrist listens and measures and watches for neurologic disorders, medical symptoms, experience, emotions, emotional expression, tremor, eye contact,  muscle tone, gait… most of these are not ever mentioned in the DSMIV.   I consider the DSMIV a necessary evil, for now.  A very clever former teacher of mine once said, "If all the copies of the DSMIV dropped to the bottom of the ocean, all the better for us, and all the worse for the fishes."  He asked that I not repeat that to anyone.  I won't attach his name, and details are changed to protect the innocent, as always...

So how do I cope with being a well-meaning witch doctor?  I write this blog.  I tear apart the pathologies of the DSMIV in the context of biology, biochemistry, nutrition, lifestyle and evolution.  For me, it is a more sensible and tenable approach than the random crapshoot of modern medicine epidemiology and the biased minefield that is psychopharmacology research.  And in my own little corner of the blogosphere, I feel all is safe and honest and going the right direction.  Most of the time.

Back to depression crashing the party.  I've talked quite a bit about serotonin, a term, I think, with which everyone is familiar.  Here is a nice article about serotonin in case you missed it. 

But serotonin is only a small piece of the whole story.  Our friendly neighborhood amino acid tryptophan can become all sorts of things - happy satiating serotonin, or enervating irritating kynurenic. Many, like the pioneering researcher Dr. Maes (who has hopped from Case Western Reserve (very respectable) to Antwerp (I'm sure, very respectable) to Thailand (well, let's reserve judgment until we know the whys and wherefores, though Thailand is a lovely place it is not a hotspot of respectable biomedical research!)) have been talking about inflammation and kynurenic for a decade or more.  And, finally, other researchers have been looking into it.  They call it kynurenine, but I'm not going to quibble.  

The new generation of researchers working out of the very respectable New York State Psychiatric Institute measured kynurenine levels in healthy controls, patients with major depressive disorders, and patients with major depressive disorders who have had suicide attempts in the past (all controls and only three of the depressed patients in this study were medication-free).  

And, low and behold, it was found that those with a previous suicide attempt were significantly more likely to have higher levels of serum kynurenine!  Let's back up - activation of the inflammatory cascade (theoretically via autoimmune or other mechanisms, like, say, to go out on a paleo limb, wheat or omega 6 fatty acids) increases the activity of an enzyme called IDO (indoleamine 2,3 dioxygenase) which will change the amino acid tryptophan into kynurenine rather than fat-n-happy serotonin. 

Serotonin levels actually have closer (negative) correlation with violence and suicide than depressed mood - and this study of kynurenine is no different - suicide attempters had the higher levels, and depressed patients without attempts had similar levels to healthy controls.  Interestingly, kynurenine levels did correlate with BMI and tryptophan levels, and more robustly in males than in females (males have a higher risk of suicide completion than females, though females have more suicide attempts).  

In previous studies, autopsies of suicide victims and  CNS samples of suicide survivors have shown increased levels of kynurenine in both.  

In mouse studies, increased kynurenine has been associated with activation of the neurotoxic (in excess) glutamate and even dopamine (which increases motivation and drive).  Stress seems to increase the activity of IDO (leading to increased conversion of tryptophan to kynurenine) and general suicide badness.  

In the end, I have to say that all that is psychologic is biologic.  And psychiatrists must keep an eye out for signs and symptoms, and while the DSMIV (and psychiatry skeptics) ignores signs, we do not.  Otherwise we remain guilty of the criticisms that the likes of Dr. Biffra will levy - which according to my comment (number 17) shows that he has very little understanding of the job of a psychiatrist. (Normally I like Dr. Biffra's ideas, but clearly he needs to consult with more expert psychiatrists if he is writing such posts!)

But ultimately I am not surprised.  Mental illness is not understood, and psychiatrists hold some of the keys to the temple.  Sometimes it is easier to eject what is misunderstood rather to absorb and understand it, regardless of biology or morality.

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A little editorial addition on 9/9/11

I thought about not writing about the ongoing controversies in psychiatry as 1) it may not be of interest to many readers (though I do have several clinical psychiatrists who follow the blog, and hey, it's my blog and I will write about what interests me), and 2) it opens me up (fairly enough) to be a defender of modern clinical psychiatry, as I am critiquing the critic.  I'm not interested in the role of defender, as certainly some aspects of modern psychiatry (and indeed modern medicine) are indefensible, and the role is ably taken up by Drs Altschuler, Nierenberg, Friedman, and Pies (among others) who have written responses to Dr. Angell's reviews.

However, I do think that critiques of psychiatry are important and, again, not entirely unreasonable.  There is a risk with an atheoretical document like the DSMIV, with diagnosis based on a list of symptoms divorced from pathology (on purpose!)  and a profit-driven pharmaceutical research community to create more and more diagnoses and make pills to fit the diagnoses.  The ultimate argument of this critique is that a lot of mental illness is essentially made up.  My main objection to Dr. Angell's stance is to this sentence of hers (quoted from Dr. Pies' article linked above), where she starts by saying that psychiatry is different than other medical specialties:  "First, mental illness is diagnosed on the basis of symptoms (medically defined as subjective manifestations of disease, such as pain) and behaviors, not signs (defined as objective manifestations, such as swelling of a joint.)"

As I mentioned above, mental illness presents with many objective physical signs that have a known neuropathologic basis, and these signs are used all the time in clinical psychiatry.  That Dr. Angell would not know this fact betrays a rather shocking ignorance.  In addition, there are biomarkers for mental illness.  Zinc is one, kynurenine now likely another, various cytokines… in fact biomarker tests are now being marketed to psychiatrists for diagnosis of depression, but it is hard to convince a psychiatrist to jab someone with a needle and spend money on the test when you can merely ask the person about the symptoms of depression and find the same answer.  I suppose it might eventually be useful in cases where people are feigning depression for monetary gain (such as a faked disability case).

And I will suggest that just because there is an objective "sign" and "known pathology" doesn't make pharmacology less of a Faustian bargain in other more "objective" medical specialties.  Sure, for reflux you can send a scope down someone's esophagus and measure pH, and the medicine used to treat it will indeed change the pH via blocking the proton pump, but is it helping the overall pathology of acid reflux in the long run?  Statins will, indeed, lower cholesterol through a known mechanism, but despite the standard line that doctors have no idea that cholesterol is less important than the statin commercials will tell you, every well-trained and intellectually curious primary care doctor I speak with on a regular basis knows that statins work via their somewhat mysterious anti-inflammatory effect, not their cholesterol-lowering effect.   And what about sulfanylurea drugs used to boost insulin production in type II diabetes?  Sure, you improve the situation in the short term (and could possibly avert some long term hyperglycemia damage) - but you are making the patient more hyperinsulinemic in the process, and looking at longer term risks of worsening diabetes, and depending on the medication, there seems to be increased risks of pancreatic cancer and heart disease.

I would suggest that "knowing" the (almost invariably incomplete) pathology and having lab tests to check gives modern medical doctors a false sense of security in many cases.  I'm not saying we should throw the baby out with the bathwater, but we can't scapegoat psychiatry without holding other specialties of modern medicine accountable in our critique as well.  Pharmacology, whether it is with psych drugs, medical drugs, or pharmacologic use of supplements will always have unknown risks along with any benefits.

Add the risks of not using pharmacology (whether medical or psychiatric) - and you have a complicated picture of risks and outcome.  One that takes good training, a bit of humility, honesty, and time to figure out.