Dangerous Experiments is the LabSpaces spot for guest bloggers. The purpose of the blog is to give new and old bloggers a space to experiment with blogging. If you'd like to contribute to this experiment, send us an e-mail or contact us on twitter at either @LSBlogs or @LabSpaces.
My posts are presented as opinion and commentary and do not represent the views of LabSpaces Productions, LLC, my employer, or my educational institution.
Please wait while my tweets load
This week's guest blogger is Tim Skellett. He is an Australian, but these days lives semi-permanently in northwestern Germany. His interests range from nature to ecology, gardening, reading, metal- and hot-glass-work, and travelling. He is a frequent contributor to the Guardian. He can be found on his Twitter account, at @Gurdur or on his blog.
I once heard a woman talk, and I've never forgotten her, although I only heard about ten minutes of her speech, decades ago. I had a job in healthcare at the time, and part of my job was accompanying patients to Alcoholics Anonymous meetings; the woman was one of a quite a few speakers at that meeting. She had been diagosed with Huntington's disease, which was a death sentence, and today still is; it was well-advanced, and meant she would die not all that long afterwards, and quite possibly in dementia. Huntingon's disease, also called Huntington's Chorea, is an autosomal dominant genetic, neurodegenerative disorder. So this woman had been handed one of life's truly nastily bad cards; one of her parents had had at least one particularly bad form of a specific gene, Huntingtin. That malformation of one gene has a great many different possible outworkings because the gene is widely spread throughout the body, although concentrated in the brain. The different outworkings can lead to different symptoms being presented clinically, which creates problems for nosology - the science or philosophy of how we define diseases. Sufferers of Huntington's often enough commit suicide, and it can be very difficult to determine if such a sufferer is suicidal owing to one possible rational response to the thought of dying in such a manner as Huntington's, or because the Huntington's itself has caused suicidal ideation through pathological brain changes, which is known to happen in some sufferers. Huntington's, like other neurodegenerative diseases, affects intentionality, our power of choice of action, through affecting the brain.
Because of that one gene that woman was going to die a rather horrible and premature death. Now she was also an alcoholic, but despite the diagnosis of Huntington's Chorea she had stuck by her decision to actually stop drinking, and she had indeed not been drinking for quite a while. As she said, she had lived much of her life without dignity, and she was determined to die with dignity. That may not make sense to many, who might prefer chemical oblivion upon news of such a diagnosis, but it made perfect sense to her and others listening to her; for many years, she had been defined by one illness with stereotypical behaviour, alcoholism, and this time round she was determined to define herself, despite a fatal disease with a stereotypical outcome.
Explaining how such decisions as that woman's are arrived at is extremely difficult for science. The problem encompasses intentionality, the area of making decisions, and there is a good deal of confusion surrounding that. There are many hard questions in science, and the best approach is bottom-up; tackling big questions by tackling a million small questions first, and then making simple models. You've heard of the various experiments that have shown that often the conscious "decision" to act actually comes after a motor impulse to act; there's too often a conflation going on in understanding such experiments, and that is, a conflation between the act of decision, and the conscious recognition of that act of decision. Because the second is often taken for the first, people will often think that that means there can be no such thing as free will as it is commonly understood, that we are all pre-programmed robots. Interestingly, our beliefs about free will or its non-existence can influence our behaviour - some will cheat more if they have been led to believe free will does not exist. Proponents of the view that free will does not exist are often fond of such simplistic statements as "science disproves the notion of free will", and that "the illusion of free will is a mere artifact of the brain's biochemistry". Neither statement is scientifically correct; in science, we are able to describe the outworkings intentionality and its pathologies; determining if a person was free not to do something is a staple of forensic psychology in courtrooms, for example. The second statement is a mere presuppposition that the feeling of free will is an illusion; often you hear the Just-So story that the illusion of free will has evolved in order to fulfill some purpose in our brains, or to make us feel better, which simply begs the question; since we have every reason to think most other animals get along fine without any illusion as to free will, just why should we need one or have evolved to need one?
It is far more parsminous, and in keeping with what we observed in daily life, to state that we have evolved self-perceiving and self-altering brain circuits, and that these circuits, through their self-altering potential, have in the human case achieved enough complexity that we do indeed possess what is commonly and legally defined as free will. We can describe some of it at a top level - that is, how we define its not working (as in forensic psychology). We can also define some of it through bottom-up research - for example through looking at the outworkings on behaviour and consciouness of one defective form of a gene, Huntingtin. We cannot as yet describe free will very well, but we can describe its pathologies in terms of stereotypical behavour and so on.
On the one hand, we have for example a very simple cause, one particular gene gone wrong, as in Huntington's. The malformed gene can have various expressions and effects, from neuronal inclusions interfering with message transport, to differing chain-reaction effects. It may be possible have a very simple cure if we are very lucky. A whole chain of very complex effects stopped by a simple cure; if we succeed in that, we will have stopped something very bad, though without understanding it or how it works, let alone exacly how it works on intentionality (for example, judging if a Huntington's sufferer is considering suicide owing to consideration of the situation, or owing to the effect on the brain of Huntington's).
Just why intentionality is so hard to get to grips with is partially explained through the theory of strong emergence- the idea that the interactions between components can lead to properties that cannot be predicted just by the study of the components themselves; for example, the properties of the brain would not then be predictable solely through studying neurons and brain structures.
So how can we explore intentionality itself more? One way of doing that is by breaking down the complex problem into a series of more soluble problems - easier questions, and that is exactly what the authors of one study publised in 2011 tried doing; they formed an experiment to test a hypothesis of breaking the problem down into three components of intentionality. The three components postulated were private, prospective, and communicative intentions, that is, only actions needed to achieve a goal, compared to intentional planning of actions involving someone else, compared to successfully communicating an intention to someone else.
Not unexpectedly, the papers' authors found significant differences in how three goups handled private, prospective, and communicative intentions; the three groups were average subjects, paranoid schizophrenics and autistics. Again unexpectedly, the researchers showed that some different brain areas can be localized for certain tasks; for example, the right temporo-parietal junction and the precuneus are essential for processing "all types of prior intentions", and the left temporo-parietal junction is only activated in situations where the subject is considering social prior intentions. Some success was gained by the researchers; they set out to prove a hypothesis of hyper-intentionality on the part of paranoid schizophrenics, that being shown by over-excitation of some parts of the brain. The researchers also discussed previous work showing hypo-intentionality on the part of autistics, shown through an under-excitation of the same relevant parts of the brain, thus showing localization of function. Yet as the researchers showed, most of the areas considered then cooperate in a dynamic network to build an internal Theory of Mind used to comprehend others. Again, we are back at levels of complexity with which it is very hard to come to terms with, or to model. The sheer diffiulties in defining and researching intentionality are very well illustrated by this study. They used a philosophical entrance to describe and dissect intention, and then sought to match that to brain area and activity; or in other words, they used one level of description - the philosophical - and sought to match that to other levels, such as the anatomical.
I've hoped to show through these two examples, of Huntington's and of the study on intentionality, just how great the difficulties are; that there are no easy answers, and that one should suspect any claimed easy solutions. One further finding is that for many effects we may only have our top level of description - for example, when describing intentionality on the whole, and free will, we may not ever be able to describe these from the ground up adequately in terms of neurology, but only in the terms we already use, whether in daily life or in the courtroom. That does not mean that such things as limited free will are not caused by neurology; it only means they are not overall reducibly describable in terms of neurology. Such concerns, as well as concerns about nosology and treatment, have led some psychiatrists to conclude that for example evidence-based medicine in its present form is not applicable to psychiatry.
To go back to the woman I heard speak; as far as I know, she died sober, and she will always remain a symbol of heroism for me, someone who did not allow themselves to be defined by a genetic malfunction. She showed she was more than the victim of a neurological accident of fate.
Bruno G. Bara, Angela Ciaramidaro, Henrik Walter, and Mauro Adenzato
Front Hum Neurosci. 2011; 5: 7.
Published online 2011 February 2. doi: 10.3389/fnhum.2011.00007. PMCID: PMC3034216
Intentional Minds: A Philosophical Analysis of Intention Tested through fMRI Experiments Involving People with Schizophrenia, People with Autism, and Healthy Individuals
Robert Levine, MD and Max Fink, MD
Why Evidence-Based Medicine Cannot Be Applied to Psychiatry
Psychiatric Times. Vol. 25 No. 4 April 2008
This post has been viewed: 4064 time(s)
Interesting questions- intention and free will.
I think the questions about the effects of Huntingtin protein on suicide ideation would require looking at studies on the effects of serotonin. Isn't serotonin typically involved in mood/anxiety disorders?
Although it still doesn't mean the malformed gene is responsible. It would be difficult to prove a link.
Good article with much to think about!
I think the effect of the products of the malformed Huntingtin are quite random in their effects; I'll look for specific effects on serotonin, though I suspect it's going to be more complex. Apparently, increased serotonin can be found in the brain after death of a HD sufferer, but mouse experiments show decreased serotonin. Why the discrepency? It may - and I'm speaking off the cuff - a simple post-mortem artefact, similar to potassium levels post-mortem; even if someone died of acute potassium deficiency, chemical changes after death mean most often a high postassium level is displayed.
Reynolds, et al. Brain neurotransmitter deficits in mice transgenic for the Huntington’s disease mutation. 1999. Journal of Neurochemistry 72: 1773-1776. Yohrling, et al. Inhibition of tryptophan hydroxylase activity and decreased 5-HT1A receptor binding in a mouse model of Huntington’s disease. 2002. Journal of Neurochemistry 82: 1416-1423.
I uill look more into this. In the meantime, I found these:
Great open discussion about the limits of neuroscience, that doesn't go into supernatural explanations at the first sign of trouble
A lot of people have trouble with the concept of emergence in any process, as they don't understand how can you get "something" from nothing. I usually use the concept of population density (1 person has no relevant population density, but a group of people have it), but it's easier for them to use conscience as a "mystery" than try to see it from another standpoint.
Another way to see it is that even though we know that biology should be based on the laws of physics, you can't really apply quantum theory to the macroscopic effects of photosynthesis (which is most probably based on quantum effects). But that doesn't mean that you can't use the tools of biology to explain the processes!
Suicidal ideation is complex too. I mean, environment has such a strong role. Serotonin seems to be important but it may not be the only thing. The fact that SSRIs don't work on all people would suggest that.
Maybe the depression part of bipolar is a totally different pathway than depression without the mania. Maybe the Huntington's gene protein is interacting in some way with these other mental processes.
Or it may be totally unrelated. Sometimes people just don't want to live a certain way or feeling a certain way all the time.
"Maybe the depression part of bipolar is a totally different pathway than depression without the mania."
I strongly believe that is the case; I would have to look up papers, but the oft-times different reaction of clinically depressed, on the one hand, and bipolars, on the other hand, to SSRI's without any accompanying medication. leads me to so strongly believe that is the case. And we know there must be different pathways for depression just from the different types of depression too. The clinical evidence is important.
this is an excellently presented discussion of nosology (comments included) -- and thank you for so many additional resources which are equally provoking!
Psychiatrists rejecting Evidence-Based Medicine? From the limited amount I could read before the pay-wall began intercepting me, was that Levine was bemoaning individual variation and the resolution of the evidence.
Surely those complaints about the limited explanatory power of current neurological understandings, as well as limitations in the understanding/definitions of illness are transient, to be further researched and understood in time.
Psychiatry, neurology, psychology are all relatively young disciplines, right? Surely any claim that they [EBM, as well as our understanding of freewill, etc] cannot be 'reducibly explained' smacks of a lack of optimism for the field (among so many other things).
That's exactly it; the writers were saying that Evidence-Based Medicine as it is currently defined is simply inapplicable in terms of effectivity to psychiatry as the present situation is.
You seem to be arguing, on the whole, from the viewpoint of what could be possible in the future; but the others are writing from the viewpoint of what the present is.
Actually, if you look at the history, psychiatry and neurology are as young or as old as physics or biology; but they're much, much harder.
As for "reducibility"; both the authors of the letter you criticise, and yourself , there's a fair bit of talking past each other here.
In any discussion of strong emergence, the properties of the particles in a system may not allow prediction of the behaviour of the system. In that way, a system may not be reducible to its component parts, but must be described in a language a level above the language used to describe the component parrticles.
Or, in other words, describing in terms of f physiclal forces, and chemical interations. and element, molecular and atomic properties, still is inadequate to fully describe schizophrenia, or again, schizophrenia is not reducible to discussion of its component particles.
Schizophrenia itself is a good example; psychiatrically, it's relatively easy; most of the time if not all you can simply diagnose it someone has schizophrenia, or if instead they've been partying too hard with chemicals. But even schizophrenia, a relatively unmistakable condition, has its problems, as when two researchers recently placed it on a continuum with it at one end and bipolar syndrome at the other end (a theory with which I fully disagree, by the way).
Cognitive feedback, influence of family and peers, all these muck up any sheerly mechanistic model, and these and other suchlike mean you must describe schizophrenia at a level above a sheerly mechanistic, consituent-particle-property level.
Evidence-based medicine is fine when you're dealing with nice simple bacteria (though even then, the Great Imitators, like syphilis, the flu, forms of leukodystrophy, the autoimmune diseases like MS, Crohn's, etc., all these can still give you a very hard run for your money).
But when you are delaing with complex levels like schizophrenia, borderline personality disorder, bipolar syndrome, etc., you must add new criteria for judgment and nosology that EBM simply doesn't have at the time being. EBM may have it later; but in a world where we know the dopamine model of psychosis, and the serontonin model of depression, to be severely inadequate (one new antipsychotic actually increases dopamine, but works well; I wouldn't be all tha t surprised if some new antipressive actually decreased serotonin), then EBM hasn't got much of a chance in psychiatry unless greatly extended and incorporating new levels of description and judgment.
I personally happen to really like nice simple asnwers too. Shoot someone full of haloperidol, then see if they can be stabilized on risperdone or something nicer, and if you can talk with them then. But in real life, nice simple answers are quite often ineffective.
Many thanks, Ragamuffin! Nosology is one of my small hobbiea; it is an amazingly interesting area, espeiclally in psychiatry.
Apologies, I should not leave a false impression. Evidence-based medicine is applicable and applied to much of psychiatry. Just not all, by a long shot. I'll also point out an example I've used in a previous blog post on nosology; some mental illnesses are mistaken as psychiatric illnesses when in fact they are psychiatric collaries of other illnesses. For example, neurobrucellosis, Lyme Disease, borreliosis-like tick infections, and so on.
You make some good, solid points, but what's the alternative? Inherent in EBM is a process, not merely an outcome. To abandon the the process because the outcomes are currently inadequate doesn't seem like a long-term strategy to better understanding or treatment
Yes, revisions of nosology and other definitional criteria, etc, make sense in order to increase their application or resolution, but even then, they are based on evidence that the current models are inadequate. EBM is as objective as we can be, and by it's objective nature, we are able to say that it currently isn't up to scratch. That seems like a reason to maintain its presence in the treatment of any illness?
I hope I'm not missing the point again...
Sorry, Psycasm, to tale so long to answer; am on road, on trip to USA. Will answer you fully in a couple of days