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.)

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.