Pills, Parlance and Plasticity

I have a love-hate relationship with my friend, and fellow Douglas blogger, Cam Zacchia. I hate Cam because he writes infinitely more interesting blogs then I do. I love him because he doesn’t brag about it.I also appreciate Cam because he stimulates my cerebral cortex. Cam loves to pose interesting questions. I wish I had a dollar for every time he has challenged me with the following: “Joe, are most mental illnesses brain disorders, or are they just “problems in living?”

I hate Cam because I could never phrase a good answer to this question. But I’ve been thinking a lot about this lately, and I think I have a good answer. So the rest of this entry is dedicated towards this end.

I know that my teachers always informed me that one should never answer a question with another question, but in this case it’s appropriate, so here goes:
Cam, is light a wave or a particular?

For those of you who may not be so well versed in physics, the question addresses a long-running paradox in physics that remains to be solved. It addresses as simple question: Does light travel like electrons (i.e., particles) through a wire, or is it like a wave that travels through water? It turns out that when you decompose light in one way, it behaves just like a wave, if you decompose it another way, it looks like a particle. Physicists like to see the world in absolutes (despite Einstein’s theory of Relativity), and so they have devoted a lot of time and effort to trying to explain how light can be both a wave and a particle.

In a somewhat similar way, mental health investigators have been arguing over a similar kind of paradox: is mental illness a disorder of the brain or is it a problem in living? Why is this “paradox” so important? There are a whole lot of reasons for this, but one of the more important ones has to do with what sorts of interventions we should be offering people who have psychological and behavioral disorders.

Most people believe that if mental illness is a disorder of the brain, it will take some form of a “biological” intervention in order to make it better. So, we have drugs for most mental illnesses, contemporary neuroscientists are actively investigating the efficacy of different types of neurosurgical interventions, and the deciphering of the human genome has brought us that much closer to the possibility of employing gene therapy, not just for mental illness, but for many types of “physical” disorders. The idea here is that “only” a “biological” intervention can correct the physical defect or impairment in the brain that is causing the problem.

If you see mental illness more as a life-coping problem, the imperative for a biological intervention seems less compelling. Most of us think it is exaggerated to give drugs to 6 year old kids simply because they may be shy or introverted. Rather, we will try to teach our children how to overcome their shyness, and expose them to situations in which they can use these new tactics in these situations.

Seen in this way, an effective “cure” for mental illness, is nothing more then teaching a young dog a new trick. It’s learning, learning that might be different in content from teaching them how to add or multiply, read or write, but the PROCESS is the same.

Psychotherapy is, in my view, an attempt to instill new learning in individuals, so that they see the world in a different light, and learn to adjust to this new world vision in a behaviorally appropriate manner. Freudian psychotherapy has, as its ultimate goal, the revelation of the so called “unconscious” conflicts that promote maladaptive behavior. The theory is that once the person learns what these conflicts are, he/she can deal with them more effectively. Sort of like correcting a bad golf swing: once you know your slice is due to pulling your eyes off the ball too early, you can practice keeping your head down (Neither Cam or I are ardent Freudians, but Cam is an avid golfer, so I think he will appreciate the example). More contemporary psychotherapies are even more closely associated with education, basing their foundation on the wealth of animal and human studies addressing the general issue of how living organisms assimilate information.

If we see psychotherapy as a type of learning, then we have a possible resolution to the “Zacchia” paradox: Who is to say that learning is not a “biological” process? One of the primary differences between a computer and the brain is that the brain has a remarkable ability to redefine itself. Neuroscientists refer to this ability as “plasticity” meaning that the brain remains, to varying degrees throughout its life, malleable, changeable, modifiable; able to change either its structure or its function in a way that allows it to assimilate new information and experience, and to use this information to alter behavior.

We have known for a long time that the brain is able to modify itself as a function of experience. In 1964, Diamond, Krech and Rozenweig demonstrated that rats raised in a stimulating environment had larger cortical volumes (the cortex is the outer layer of the brain that stores information) then those that were not (M.C. Diamond MC, et al. (1964) Journal of Comparative Neurolology, Volume 123, p.p. 111-119). More importantly, recent evidence has shown that we can see the same structural changes in the brain following successful pharmaco- or psychotherapy. There are many illustrations of this, but let me focus on one of the earliest, demonstrated by an acquaintance named Lew Baxter (L.R. Baxter Jr. et al. (1992) Archives of General Psychiatry, Volume 49, p.p. 681-689).

Lew first scanned the brains of a group of people suffering from Obsessive-compulsive disorder (OCD). For those of you who don’t know, OCD is a debilitating disorder defined by a thought that you can’t get out of your head (e.g., I left the stove on at home) that is so pervasive that it controls your entire life (I go back repetitively and consistently check to see whether the stove has been left on). The classic illustration of OCD involves those poor individuals who continually wash their hands because of a fear of germs. Excessive hoarding is another good illustration of OCD.

These initial scans indicated that the patients appeared to have abnormally high levels of activity in an area of the brain known as the caudate nucleus. This was interesting, because we know that the caudate is very much involved in intitiating voluntary and complex motor behavior, and is an ideal candidate for explaining the repetitive and pervasive nature of compulsive behavior.

Lew then assigned different people to either pharmacotherapy alone or psychotherapy alone. Some people in both groups got better, some did not. Lew scanned all these people a second time, and lo and behold, he found that caudate activity decreased in those people who got better, but did not change in those who remained ill. More importantly, the caudate changes were the same for those people who responded successfully to either pharmaco- or psychotherapy.

Have a gander at the top two brain scans in the picture below (you’ll have to click on it first to enlarge it), and pay attention to the area pointed to by the white arrows. That’s the caudate (more specifically, the head of the caudate). Red means that the caudate is very active, yellow means it is less active. You can see that in both cases, there’s a lot of red in the caudate. And that’s not too surprising, since these are the scans that were taken before any treatment.


Now look at the scan in the lower left of the picture, that’s the scan of a person who responded successfully to pharmacotherapy. compare this with the scan right a bove it, which is the scan of the same person prior to pharmacotherapy. In the bottom picture, the area is yellow, showing that drug intervention reduced activity in the caudate. But now the piece de résistance: Look at the scan in the bottom right of the picture. This is the scan of someone who responded successfully to psychotherapy. Compare that to the scan above, which is the same person prior to psychotherapy. Note that the arrow in the bottom scan points to a predominantly yellow (not red) area, meaning that psychotherapy was also able to reduce caudate activity. So, psychotherapy induced the same brain change in successful responders, independent of whether they were given pharmaco- or psychotherapy.

You may be wondering why some people did not respond to either form of intervention, and that is an important, albeit unanswered, question. But I think that the point has been illustrated: you can, at least in some cases, improve the lot of some people suffering from mental illness by giving them pills, or by talking to them and teaching them new things. And, if that’s the case, what kind of intervention should we be asking for from our mental health providers? Well, I’m not a betting man, but it makes sense to me that if two different interventions do the same thing, then we are doubling our chances of a successful treatment by combining psychotherapy with pharmacotherapy, particularly for those disorders that are defined by more intractable and severe symptoms and behaviors; in brains that may have lost some of their ability to remain plastic. If you’re not comfortable with hunches, rest assured that the scientific evidence has demonstrated that the highest chance of successfully treating any mental illness stems from a combined thrust of pharmaco- and psychotherapy.

Even Cam would agree with that!

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Posted in Brain, Human, Mental health.

Posted on 08 Sep 2008

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3 comments to Pills, Parlance and Plasticity

  1. Catherine
    On Sep 8th 2008 at 17:30

    This entry was fascinating, I like the fact that it was pretty “technical” (to me, at least!) but still very accessible! I really learned something today! Thanks!

  2. Camillo Zacchia
    On Sep 10th 2008 at 00:02


    You should know me well enough to know that to me EVERYTHING IS RELATIVE. I’m the ultimate wishy washy guy.

    I actually have a half written column on my computer called “The wave-particle duality of life,” but that will have to wait for another day.

    Great post and I agree with you (of course). You got me thinking too much so I had to put in my two cents and discuss the topic in my own blog.
    (You made me stay up late to write it so if I end up sleep-deprived tomorrow I may actually be obliged to give you a problem in living!)

  3. Camillo Zacchia
    On Sep 11th 2008 at 09:59

    You’re right. I sometimes use the term medical and biological interchangeably. I know it is not the case. In fact, that is why I start with the example of how a name can change our brain.

    My argument is that everything is biological. All processes contribute to that biology. The reason I like to differentiate “biological” from “psychological” is because some processes are PRIMARILY psychological (learning, experience, instruction, etc..) and others are PRIMARILY caused by by more “biological” means (nutrition, disease processes, etc.).

    The manifestations of that biology can have a psychological face.

    I just want people to understand that there is a big difference between a disease, such as Alzheimer’s (or Schizophrenia) where the search for a solution lies within a better understanding of brain function (and malfunction), and other types of problems that create suffering, such as the depression that follows a loss (such as what I describe in my post).

    Of course I know that a better understanding of the brain may also help the person with a broken heart but A) we’re a VERY LONG way from having that understanding, and B) any problems that arise from normal social interactions (such as a love gone wrong) can often be helped by other social interactions (support from friends, therapy, etc). This type of social interaction, while nice and probably helpful, will not cure Alzheimer’s or Schizophrenia.

    If I had cancer, of course I would feel MUCH better if my friends and family showed love and support. If my doctors and nurses were compassionate, I would feel more human. Having said that, if a doctor with a terrible bedside manner actually could give me a pill that would cure me, I would still insist on seeing him or her because, in such a case, the best way to change my biology is through a medical means.

    So, yes, it is all biological. But I use “medical” to refer to problems that can be considered diseases in the traditional sense, and “non-medical” for problems that can occur when the brain is working within relatively normal parameters.