Stress and diathesis OR psychological tales of wise Achilles

In my last entry, I lamented the lack of progress we have made in understanding the causes of mental disorders. Before I get accused of being an eternal pessimist, let me clarify the point I was trying to make. All I was trying to do was to emphasize that we need a lot more research in the area of mental health before we can start making significant head-way. Of course, the same can be said about maladies of the non-psychological variety, but I can (but won’t) bore you with an array of statistics demonstrating that research into mental health is about as well-funded as research investigating the wing speed of the African swallow (Monty Python aficionados should understand that last reference! If not, go out and rent Monty Python’s Holy Grail, best anti-stress film made!). Yup, it’s pretty difficult trying to dig up funds for research projects with schizophrenia or depression in the title, you’re chances are significantly improved if you can manage to include the term cancer, or diabetes, or even obesity. So a relative lack of funding can explain part of the massive crater that is our understanding of the causes of mental illness, but it’s not the whole story.

Which brings me to the point I want to discuss in today’s entry: Before you can start identifying the causes of a disorder, you have to have some idea of what you are looking for. It will also tell you whether you should be looking for something simple or complicated. Finally, it gives you an idea of where you should be looking. So this is why I think there is significant reason to be optimistic about additional research: we now have an idea of what we should be looking for and where we should be looking.

In the 1950s and 1960s, in large part because of the influence of Freudian theory on psychiatry, the primary thing we looked for as a cause for a psychopathology was environmental. So, schizophrenia was thought to arise because mothers of schizophrenics were thought to send them mixed signals when they were young, and the mixed signals subsequently destroyed their ability to think logically, or at least realistically (the so-called Double-bind hypothesis). Depression resulted from loss, be it of a loved one, of status, of property. Anxiety arose between person’s desires and society’s disapproval of those desires.Â

Around the same time, a different brand of investigator was looking elsewhere for the causes of psychopathology: the genes. The method was elegant in its simplicity (albeit difficult to conduct in practice): find twins that were raised apart (due to adoption), and look for “concordance”: that is, if one twin has a pathology, does the other one have it as well? If both have the disorder, they are concordant, if not, they are discordant. Finding twins raised apart is one though task, but the reason why it is difficult to conduct this research is because, in fact, you needed to find two types of twins: identical (or monozygotic) and fraternal (or dyzygotic) twins. Identical twins come from the same egg fertilized by the same sperm, the fertilized ovum then separates into two. So, identical twins share exactly the same genes. Fraternal twins come from two different eggs fertilized by two separate sperm. So fraternal twins do not share the exact same genome, they are more like siblings. Now the clincher: find the rate of concordance for a given pathology (e.g., schizophrenia) in identical twins, and see if it differs from the concordance you see in fraternal twins. The difference between the two is likely due to genetics. Why? Presumably, since all the twins were raised apart, in different environments, any differences between concordance rates cannot be due to the environment (a reasonable assumption, but one that is not without flaws, as a future entry will discuss). So the difference in concordance has to be in the genes: since identical twins share 100% of the genes, and fraternal twins less then 100%.

Now, there is nothing intrinsically wrong about either the environmental or the genetic approach to illness, except to say that when it comes to mental illness, it is incomplete. It is incomplete because it only tells part of the story. The concordance rate for schizophrenia in identical twins is only about 50%, much higher then the 14% concordance you see in fraternal twins, but clearly much less then the rate you would expect if schizophrenia was exclusively genetic.

Before you environmentalists start bragging, let me mention that the evidence in favor of a purely “nurturing” explanation of pathology is also incomplete. We all know that loss of a loved one, for example, is a strong indicator of depression, but we also know that not all people who suffer such a loss will become depressed (they will definitely go through a difficult period of mourning, but a full-blown depressive episode is not the invariant consequence of loss). So, this raises the obvious question: Why are some folk more sensitive to loss then others? We have known these things for at least 40 years now, and they have indicated that in order to have a better, more complete grasp of the routes of pathology, we need to somehow find a framework that puts them together. And that framework has been emerging during the course of my lifetime: it’s known as the stress-diathesis model.

The word diathesis stems from the Greek “dithesis” meaning arrangement or disposition. In modern dictionaries, you are likely to find it defined as “a constitutional predisposition or tendency, as to a particular disease or affection”. In short, it is a vulnerability, or susceptibility to a disorder. The vulnerability can be quite small or it can be quite pronounced. But the thing to remember about vulnerability is that, whether it is weak or strong, it needs to be exposed, it needs a trigger to activate (or exploit) it. Hence the stress part of the model. Stress is the environmental or psychological trigger that exposes the diathesis.

So psychopathology is not just the simple effect of one thing or the other, but rather a combination of things. How must these things combine to throw someone into the throws of a mental illness? If the vulnerability is strong, a relatively weak trigger can activate it. If the vulnerability is small, it will take something very peculiar (either in terms of strength, quality or quantity) to trigger it.

Imagine the average ancient Greek warrior, not especially strong, nor well protected by the armor he was provided. A well directed arrow or sword blow to many different parts of the body could be fatal. Now recall Achilles, the greatest and strongest of the Greek warriors, who was blessed with near invincibility because his mother, the immortal sea-nymph Thetis, had the wisdom to dip Achilles in the river Styx when he was an infant. This simple “baptism” made him impervious to assault, with the exception of his heel, the area his mother grasped in order to dip him into the water. Unfortunately, when she pulled him out, she neglected to dab a little “Styx lotion” on the unexposed area. As an adult, Achilles was one tough hombre, defeating all adversaries, including the equally impressive (but more vulnerable) warrior Hector. Yup, it took a very special circumstance to expose the one minor vulnerability that Achilles suffered from: a poison-laced arrow directly to the vulnerable heel; the arrow was granted divine guidance by none other the then Greek god of war, Apollo (turns out Achilles murdered someone inside one of Apollo’s temples, an act Apollo did not really appreciate, and for which he was happy to avenge).

If you don’t like mythological illustrations of the stress-diathesis model, consider the the illustration below. If you happen to be blessed with a well developed body, you can probably resist a lot of weight. It is worth noting, however, even the strongest of organisms has a limit: a weight which cannot be resisted, and which will crush. If you are like most humans, that threshold is much lower, and if you are the proverbial 98-pound weakling, well, don’t try taking out the trash after Christmas.

Framing mental illness in this way has given rise to some pretty impressive research, not only in terms of understanding the underlying causes of mental illnesses, but also in terms of developing novel ways of treating these disorders. I’ll consider some of these breakthroughs in subsequent entries, but to close this (already too) lengthy discourse, I want to point out there is a strong inter-personal implication to the model.

Achilles was by no means a humble man; he boasted of his prowess and accomplishments. But, near as I can tell, he never ever belittled his more vulnerable companions or chastised them for being unable to resist a club to the head, or a sword to the heart. I like to think that Achilles appreciated comrades who tried the best they could, even if they could not aspire to the heights he could achieve. Bravo, wise Achilles! It is one thing to criticize for a lack of effort, it is entirely another to chastise or even stigmatize someone who happens to be less capable then ourselves in dealing with the ordain stresses of every day life.

Someone who used to be very close to me once expressed the belief that depression was a “sign of weakness”. No, not a weakness, just a vulnerability, a blemish, triggered or exacerbated in large part by people who believe it is a sign of weakness; people who consider mental illness to be nothing more then poor moral fiber, or a lack of initiative. In part, the stress-diathesis model has taught me the folly and psychological pain imposed on the mentally ill by attitudes of superiority.

So, if you know someone with a mental illness, aspire to the wisdom of Achilles. Recognize and accept their vulnerabilities, because even if you believe you are invincible, some day a poison arrow may just find it way into your unprotected heel, and you may want some advice and support from those people around you who have already been wounded.

Tagged as cause, environment, Freud, gene, mental illness, stress, stress-diathesis, treatment, vulnerability.

Posted in Brain, Mental health.

Posted on 08 Jan 2008