woensdag 9 december 2009

What Is This?


I left these pictures standing for a couple of days without comment. I am curious what viewers may have thought about them, without any further knowledge (well, most of you, I'd guess).
What you seen is the human brain, 'rendered' in as good as a 3-D-like presentation as could be achieved. Do not mind about the detailed structures present in the green area, think of that mass as our brain.
Now, a bit of theory. I already wrote about the deficits in inhibition inherent in OCD. Nor intrusive thoughts, nor repetitive behaviours can be controlled or dismissed at free will in a patient. What is wrong here?
A chief task of our brain is the processing of information. That information can take on an unlimited number of guises: rational interpretation, rational instructions, emotional information (e.g. on the states of various moods, or pain... any type of feeling, in fact), information on numerous bodily states (hunger, thirst, sexual arousal), our movement... everything that has to do with ourselves in any way, and with our interaction with our environment, including other people.
This processing occurs in neuronal circuits. Brain parts have their identity by interaction with other brain parts. You can't take a brain part out of the whole, and then claim that it still is busy processing a particular piece of information... because (apart from withering away quickly) it lacks input and the possibility for output. Perhaps you've heard of the term wholism, referring to a quite popular worldview that the world, or the universe, or a human community, can't be reduced to single entities; there's considerably more to the whole than to the sum of its parts, so to speak. Well, the brain is an excellent example of wholism.
There is one particular neuronal circuit that seems to be somewhat out of order in OCD. This is called, very poshly, the cortico-striatal-thalamo-cortical circuit, a.k.a. the CSTC-circuit (you may want to impress your G.P. with that sometime!).
Core structures in this circuit are areas in the brain cortex. Well, our circuit starts with the cortex and ends with it. Makes sense. Two parts of the cortex are very important in our model. I must use Latin once again: these parts are the anterior cingulate cortex and the orbitofrontal cortex, or: ACC and OFC, respectively. You don't have to learn these names by heart.

Is OCD Heritable?

Partly. As I wrote: the disorder is very much a combination of genetic susceptibility and life events of a highly distressing nature.

Now, you may ask: interesting, but in how far is it inheritable? What are the chances that, if my dad suffers from it, and both our lives are somewhat comparable, I myself will develop OCD?

I would say: moderately to considerably. With an emphasis on 'moderately', simply because that is the assessment that most scientific articles share.

Studying heritability of psychiatric disorders is very difficult. See: if I have a somatic (read: bodily) disorder, like a deficit in the production of a certain substance, tests are often rather simple and deliver a quick 'yes-or-no' type of answer. And then proper treatment is a matter of protocol. And frequently we see the presence of such an illness transferring from parents to offspring, or occurring after having 'skipped' a generation.

Not so in disorders of the mind, of the psyche. Although most of the experts agree on the idea that our brains are the 'living room', the substrate, of our thinking and feeling, that does not mean that there is a simple method to search the brain for what is wrong in OCD. Making pictures of the brain improves on an almost yearly basis, yes. But making the right pictures and interpreting them correctly is specialist work. A central question is for instance: is what we think we are assessing truly the same as that what we are assessing? If we see a difference between brain areas of patients with OCD, and healthy control subjects, what does that difference stand for? Which substance is abnormally present? Which brain area is too active, and if so, what does that activity mean?

So: looking into what is actually operating 'not normal' is difficult enough in itself. But moreover: mental disorders are usually diagnosed highly subjectively. The patient reports what he or she feels, experiences, and how that impairs the quality of life. The doctor will duly take note of that self-report. Almost always the patient will fill in some sort of rating scale that is designed to profile the exact features and gravity of the disorder; in OCD the standard index is the so-called YBOCS, the Yale-Brown Obsessive-Compulsive Scale. If one exceeds a certain number of points in the personal scale, the diagnosis will be OCD.

I know, this is a long story. But it is important to know how difficult it is to correctly assess OCD in the first place. I have to stress that the subjective diagnosis by the clinician, and his interpretation of the rating scale, is the dominant procedure: a patient who clearly is troubled by OCD may present with no detectable abnormalities in the brain if subjected to a brain imaging technique and/or a biochemical analysis.

It is not a 'yes-or-no' thing. Even the standard rating scale is subjective in the end. Patients may have waxing and waning of the symptoms. One day leaving the house may be simply impossible as a result of inescapable checking compulsions, and another day it may be reasonably attainable.

OK. Back to the beginning. In how far is OCD inheritable? Van Grootheest, an expert, and his group did a truly comprehensive study on all essential studies of OCD occurring in twins. You will understand that identical twins are an ideal object for study here, as these twins share so many characteristics on genetic grounds.

Their conclusion was that the closest relative of an identical twin has a chance in the region of 27-47% for developing OCD, if his/her brother/sister presents with OCD. Now, that is considerably more of a chance than the risk for any average person, which, as we saw, is about 2-3%.

This is an indication for the heritability of OCD. As they say: it runs in the family.

Although the nature of the disorder may vary from one generation to another (e.g. a daughter of a mother with washing compulsions may develop an ordering compulsion), it is more likely that the inherited features of OCD are of the same dimension.

(PS: if a reader thinks there are mistakes in the text, or too many difficult words, or too few, please write in. As this is my first effort of this kind, I make mistakes, that is certain. Or rather: I will always make mistakes, as we all are prone to do.)

donderdag 3 december 2009

Genes and Environment

Hello to all -
In neurobiology, there is a shorthand description of something that most of us will have some grasp of, even if one is not trained in biology. The formula is: 'G x E' (genes x environment). It means: a person may develop a condition due to two things:
1. Genetic susceptibility. Many disorders and diseases are somewhat 'preprogrammed', in a veiled way. Our DNA is the nuclear structure in all of our cells that carries the instructions for the making of proteins. Proteins play an enormous variety of different roles in all organism. They are also named: polypeptides, and are chains of tiny building blocks, called amino acids. There are 22 so-called standard amino acids. DNA is the blueprint for the eventual structure of proteins, it determines the exact sequence of the amino acids in a protein. Now, suppose something 'went wrong' in the DNA code. One element in it, let us call it a nucleotide, has for one reason or another been beplaced by another. This may be the cause of one amino acid in our protein being replaced by another; the 'programme' instructs the building of the protein in a slightly different way.
This replacement can have a great impact. Because important proteins in our whole body, including the brain, may have been altered a bit in their structure. Whilst this is not always threatening (it can even be an improvement in some cases), it can hamper the proper functioning of that protein.
If we consider that the molecules in the membrane (the 'wall') of our nerve cells are also proteins, we begin to understand that if these proteins are altered in structure, they are in theory also altered in their function.
A highly interesting, and replicated result in science is that a certain protein in nerve cells, called the glutamate transporter, can be altered in the way I described, and moreover, this alteration is much more often seen in patients with OCD than in healthy control subjects. The protein (or rather: set of proteins) in question have the following function: it is responsible for the transport of the amino acid glutamate back into the nerve cell. Glutamate is the neurotransmitter (messenger molecule) most present in our brain.
Now we see a connection. Suppose that in OCD patients, the transport of glutamate back into the cell is defective. This transport is important for the normal function of our brain. Moreover: if present in too high quantities (levels) outside of the nerve cells, glutamate can become damaging. It can be responsible for a degeneration of nerve cells themselves and the protecting cells around them (the so-called glia cells).
We have seen that an ever so tiny change in genetic coding, our blueprint so to speak for all of our body structures, can have a considerable consequence for the proper functioning of a certain part of our body, here that part is the brain.
To recap: there is a possible connection, called an association, between an altered protein structure, the glumate transporter (which has the posh name of SLC1A1) and the occurrence of obsessive compulsive disorder.
Research here is difficult, time consuming, pricey, and it is quite hard to find homogenous groups of patients. The latter demand is important: if I throw in checkers, hoarders, washers, and order-addicts into my experimental group, women and men, children and adults, medicated and unmedicated people, then chances are very slim that I will obtain any trustworthy result. So there is a need for a precise selection procedure.
The above problems are the reasons that research takes a lot of time. That is why we have little reliable information about the special role that serotonin (another messenger molecule) in all probability plays in OCD. We do know that serotonin reuptake inhibitors work in about half of all OCD patients. But how do they work? There is, in the serotonin system, a comparable molecule (protein) as there is in the glutamate system. Its name? You will know: the serotonin transporter. We even know that this molecule has various possibel sites for mutations within it, and there even exist 'missing parts' in the genes that code for this transporter. But there has been no consistent result in studies that try to link the serotonin transporter to OCD.
Which is puzzling.
2. Now, here is the second part of the formula 'G x E'. The 'E' means 'environment', as we saw. It was observed that not all people that carry the mutations mentioned above, or other aberrations in essential proteins in the brain, actually develop OCD. Moreover, when researchers decided to interview patients about their life history, an interesting fact presented itself: in all likelihood, dramatic life events may 'trigger' the occurrence of OCD in susceptible people. In other words: you may have a genetic disposition for OCD, but you may at the same time not develop the illness itself. Simply put: you seem to have been lucky. Other people who have the same genetic disposition may develop OCD; and then chances are that there are events in their life history that 'unpacked' the disorder. Such events may be: problems at childbirth; physical and/or sexual abuse in childhood; emotional abandonment in general; and also things of a less severe nature that particularly impact on one's private sensibilities.
Most of us will know that OCD is also called an 'anal fixation'. Funny that... Sigmund Freud developed that concept a century ago; he had an all too severe potty training in mind, that could traumatize children and would make them into all too precise, neurotic, obsessed adults in the long run, with a strong tendency towards cleanliness, collecting, checking. Psychologists used this idea throughout the last hundred years, and still do, but its use is on the wane. In fact, 'anal fixation' and 'anal personality' have become staple phrases for the lay population, and are being used in TV sitcoms and silly quizzes.
I gave the example of Freud because it is a vivid illustration of a life event that can eventually (and potentially!) be a factor in the development of a mental disorder.

vrijdag 27 november 2009

Lack Of Inhibition

Today I would like to address a central phenomenon in OCD. Most forms of the disorder have at their core: a lack of inhibition.
What is that? you may ask. I feel contrained by the affliction, it damages my life. I am nervous and unable to do things I want or need to do! And you, Sir, dare call this: lack of inhibition???
Let's see... why is 'lack of inhibition' a valid concept then?
OCD patients have intrusive, obsessive, fearful thoughts. They seem to circle around in the head and don't flee when you want them to. You cannot suppress them. Now, the latter observation is crucial. OCD patients usually know that they have something that most others experience too, once in a while. But patients have it in excess. Trains of repetitive and unsettling thoughts, about something, or more things, that 'aren't just right' and need be put right. The nature of these thoughts is: harm, damage, lack of order and symmetry, lack of cleanliness and hygiene, lack of completeness, fear of intruders in one's territory, and so on.
What sets patients apart is precisely: the capacity to suppress the thought patterns, even if these are recognized as nonsensical. This I call: lack of inhibition. The thoughts cannot be inhibited qua their presence. They lead a life of their own.
We take one step further. Patients respond to the thoughts by performing rituals. This is the behavioural response, it serves to reduce fear and anxiety. Which it eventually does... at a price, a steep price. The rituals are time-consuming, and incapacitating. There is no escaping them. They must be appeased, it seems, tamed, like a wild animal that has to be put at rest, with a lot of effort. Again, we lack inhibition. We must perform the ritual to its end. Stopping halfway is impossible; if we do that, the worrying thoughts keep on rearing their ugly heads.
I will conclude for the day with three remarks:
1. lack of inhibition is represented, matched, by certain abnormalities in brain circuitry and connectivity. It is highly intriguing that the descriptions I gave above, about thoughts and behaviours, have a mirror image in our brain, and refer to regions that normally perform the tasks that are so 'deformed' in OCD. Personally, I haven't often seen such a match between symptoms and brain regions in psychiatry. It is almost as precise as: hey man! I can't walk! Look, my leg is broken!
2. the level of incapacitation in OCD is very high. The World Health Organization (WHO) ranked OCD in its Top Ten of most incapacitating disorders worldwide. Unfortunately, few clinicians and therapists know this. Even worse: I have met various clinicians who stated: we can treat OCD successfully today! This is evidently untrue, as I will prove. Mind, I write this not to make people hopeless and sad, I do so because false promises are the worst kind of promises. And I think that people in clinics who predict unrealistic outcomes may have an unrevealed interest on the side: they may have a financial involvement because they practise a certain form of treatment with their patients, and want to attract probands.
3. if we calmly look at the various forms of OCD, we see a pattern emerging. Take: checking, washing, counting, hoarding, religious obsessions, sexual obsessions. What do these forms have in common?
(Jeremy Paxman commands me to give the answer right now...)
The keyword is: evolution! OCD has a strong link with the capacities humans need to preserve themselves, to rear their children, to procreate, and to provide safety. It is about: territory protection; about: hygiene; about: stocking food and stuff for bad times; about: praying to God; and about many more related issues.
True, dat. But why OCD then? Well... the above beautiful qualities (hey, sex is great!) have spun out of control in the disorder. In fact, they have become grotesque and have exceeded all boundaries. That is the sadness of the affliction.
We OCD patients thus are normal. Abnormally so...
(tbc)

donderdag 26 november 2009

Is OCD A 'Mental' Problem? Or The Result Of An Abnormal Brain?

I sought to make a provocative title expressly here. I want to say: in how far do we have a concept of 'mind' and 'consciousness', and also 'memory'? Does trauma play a role in OCD?
Many OCD patients have a lot of shame about their condition. They seek to hide it, and to function as 'normal' as possible. Within certain boundaries this is possible, although the personal cost is enormous. If one needs to check doors for half an hour before leaving the house (for school, work), and then again in the late noon (when visiting friends), and again before bedtime, then already the disorder is extremely taxing. Nervousness, fear, sweat, tiredness: all are the direct result of OCD. Often there is no time for hobbies. Rearing one's children may be too heavy a burden, with serious conflict as a result, the partner may think of a divorce. Not because he or she fell out of love with their significant other, but because he or she cannot muster the courage and energy anymore to cope with the partner's disorder.
You may not believe this: the average time that elapses between onset of symptoms and the decision to visit an expert is about 17 years!
Another serious thing: contrary to what is the case in other types of psychiatric afflictions, the average OCD patient knows very well that his or her obsessive thoughts and behavioural rituals are 'not normal'. The patient has a good 'meta-cognition': this means that the subject can 'look from a distance to him/herself', and say: hey, what I am doing is strange and not rational. Because checking a lock one time, and one time only, is enough!
A posh term for this is: 'ego-dystonic': the disorder does not blur boundaries about what is normal and what is not. The thing is: the patient can at the same time not limit the ritual to what he or she would perceive as 'normal'. The ritual 'takes over' every time, has a life of its own, and only when the obsessive fears are 'quenched', then it can be ended.
Am I mad? This is the question that patients are vexed by. I state here: NO. You are not mad. You have a good sense of the normal and the abnormal. You do not belong in the 'nuthouse'.
These remarks must be seen in context, and not as insulting to psychiatric patients. They should be seen as comforting and inspiring. To make a move in the right direction.
'Madness' is a rather old-fashioned word, a term that can imply so much that it is rather meaningless. The greatest artists over the ages had their 'divine inspiration', or: madness if you will. But the serial killer is mad also.
I want to say: psychiatry, and neuroscience (neurobiology), have made great leaps in the field of this type of disorders. Fantastic techniques are available to visualize on a screen how the brain of OCD, depressive, and schizophrenic patients work. And they can show how nerve cells work in different ways in patients, compared to average people. We know how the blood flow in the brain is altered in obsessions and rituals.
Try to see OCD like a skin wound. Tissues and blood flow work differently. We can see how they work differently. And this is the first step towards finding a real solution for a 'problem in the brain'.
You may not believe this: almost all types of medication that are prescribed in OCD were not designed to combat OCD. They were synthesized to counteract all kinds of diseases; but in patients with obsessions and compulsions, there was a very surprising, unexpected effect: the symptoms of OCD were alleviated!
Only now are we able to:
1. find out what exactly is functioning in a different way in the brain, in OCD;
2. design proper types of medication targeted exclusively at these dysfunctions.
And this means that in the next years therapies will become available that have much less side effects than current medication still does.
Hopeful, isn't it?

woensdag 25 november 2009

About myself

I am a man aged 50. Single. In my puberty I had recurring obsessions with certain themes: people should not touch some of my clothes, and these should stay 'pure', in their new state. Because I attached a lot of meaning to them in terms of my appearance. Also: I had a terrible early morning mood. Furthermore, I was enormously afraid of losing my hair. Now, I know that everyone has these things to a certain degree. In my case, however, I can say that they threatened my happiness to a large extent. If something 'was not right', then I got very, very sad.
After I began at University, things got worse. I rented a room with a landlady in my new hometown. I was lonely. When I left that room on Fridays, to go to my parents for the weekend, I had to check electrical household appliances, current sockets in the walls, door locks. To such an extent that I could not predict how long the measures would take, nor which train I could catch to go to the parental home. I arrived late almost every week. Terrible. Apart from having to run to the bus station, and to phone my folks that I would be late again, there was the down mood at home: he's not in time for dinner as he promised to be.
Just before I was to complete my M.Sc. degree, I got mentally 'frozen' by the disease. I couldn't make any appointment anymore, save for the ones where I calculated in that I would have to start 'checking' about a full hour or even more before leaving my apartment. I checked: faucets, stoves, windows (all had to be fully closed), flasks of shampoo, bottles with shaving cream, after shave, cupboards (closed?). I was terribly afraid that either (1) I would forget to check an object (leave it out of the ritual, so to speak) and also forget to close the front door, or (2) that someone (the landlord) might sneak in during my absence and damage or steal a beloved object. Whilst away, I thought about these dangers almost continuously, and frequently checked if I had my keys with me. Even then: when I was at home strange fears plagued me: had someone (even a dear friend) taken my keys in the pub, for instance, gone to my room, done damage or stolen something, and then returned to that pub, and hung the keys back again at my belt, all this with me not noticing it? Even with all the power of logical reasoning that this was impossible, I could not drive away those fears. Late in the evening, I drunk alcohol to alleviate my pain. Sometimes I had this sadness: it had happened. The worst had come true. So I had to make a fresh start after that disaster. Which was, as I very well knew, a harrowing fantasy.
All this is only the surface, the tip of the iceberg.
(to be continued)

dinsdag 24 november 2009

Obsessive-compulsive Disorder (Beta)

Hello to everyone -

welcome to my weblog about obsessive-compulsive disorder. My aim is to provide information and to learn from the contributions of visitors who supply their own knowledge, experience, and opinion on this unsettling and disabling affliction. Although psychology, psychiatry, and neurobiology in the strict sense have made great progress in the past decades in unraveling the many factors that contribute to the condition, it can be stated that the general public knows little about it. Too little, in my view. This situation leads to unnecessary suffering for patients and their families and friends alike. Patients may hide OCD (as it is known) for many years. This way, relatives and friends can become 'co-patients', much as is the case in alcoholism. Furthermore, the longer a patient hides OCD, the more damage is done to his or her social and professional life. Major depression can be the result of protracted suffering from OCD - but OCD and depression can also exist in such a close relationship that experts term it: co-morbidity.

If anyone feels like writing in at this early stage, feel free to do so: it can of course be done anonymously, so there's no wariness needed in this respect.

I hope this thing works!