Trevor Robbins: What causes OCD?

In this edition of Titans of Science, Chris Smith chats to Cambridge neuroscientist, and expert on OCD, Trevor Robbins...

Chris - What do these different bits, you said there are multiple areas of the front part of the brain, what are these different areas doing and how are they controlling that core region, the striatum, to produce the behaviours that we see both in health but also in disease?

Trevor - This is the million dollar question. The frontal lobes in general exert what's commonly called executive function. In other words, it's a set of operations of controlling functions which affect behaviour in different ways. One of these is called working memory, which is our ability to remember phone numbers and then act on them. Another function is a very important one, inhibition. In other words, stopping you blurting out stupid things or stepping out into the road or making a stupid purchase. Another aspect is cognitive flexibility, the ability to organise your time to multitask, to switch effectively from one activity to another. And very importantly, two of our main controllers over behaviour are the so-called goal-directed system and the habit system. This cognitive flexibility has to constantly balance these two systems in order to optimise our behavior.

Chris - And how does that age and grow? Children characteristically do not have a lot of those things that you just mentioned, those traits, whereas hopefully you and I do, some of us more than others. So how does that change with age then?

Trevor - It's absolutely key because the frontal lobes, the frontal cortex, is the last bit of the brain probably that develops. And it doesn't really properly mature, I suspect, until you're about 25.

Chris - People say that this happens at different rates in boys versus girls. Is that true or is it just that all of us have still got a lot of growing up to do until we are in our mid twenties?

Trevor - There are subtle differences in boys and girls, but overall the point is that the frontal lobes aren't very operative very early on, for example, when you are three or four. That's an age where actually compulsive behaviours often begin to emerge. They may go away as the child develops and their frontal lobes mature, but in some cases they may persist. Now, the fact that we get more rigid as we get older is probably because the frontal lobes are diminishing in their role. Indeed the frontal cortex is one of the most vulnerable regions of the brain to ageing. So basically then you release all of these behaviours, which previously you've been able to regulate and keep under control.

Chris - So a person who gets dementia, for example, and it affects the volume of the front part of the brain, is that why people often say they seem to regress and they become childlike in some behaviours? Is that sort of unleashing what's always there, but it was previously kept in check by the frontal lobe?

Trevor - Well the most graphic example of that is the so-called frontal dementia, which is distinct from Alzheimer's disease. It's another kind of dementia and it's often expressed behaviourally in very outrageous ways. So for example, one way it's expressed is if you are eating in a restaurant with a relative who's got frontal dementia, they may lean over and grab your steak from your plate. Or they may do unmentionable things in public. So they completely lose their inhibitions because of the relaxation of the frontal lobes and as a consequence of its degeneration.

Chris - Why does that part of the brain burn out more quickly then? Has that evolved? Is that an evolved trait or is it just because it's so busy in your average person that it does clap out rather like a car being driven with the pedal to the metal all the time?

Trevor - I think you've answered it Chris. I don't think we know absolutely for sure, but it's probably to do with the fact that the frontal lobe uses a lot of metabolism and therefore is very vulnerable to energy demands.

Chris - Now returning to where we started, which is the link with diseases, you've explained all these important jobs it does and that normally it holds our behaviour in check. So how does it allow some of these conditions to manifest then like OCD?

Trevor - Well, our hypothesis would be that the weaknesses develop in its function basically. There's evidence in some cases of reduced grey matter in the frontal lobes. There's also evidence of what we call impaired connectivity. In other words, its connections with other regions, which you can measure in humans with brain scanning. And so because of these failures of communication over other areas, then you are going to get this dysregulation of behaviour.

Chris - Talk us through then, if one subjects people who've got these sorts of conditions like OCD to the sorts of brain scans you're talking about, what is wrong with the connectivity that means they tend to have the problems that bother them?

Trevor - Well that's again another million dollar question. We think that there's actually an imbalance in the frontal lobes and some of the areas become overactive and some become underactive. That's basically the story. As a means of therapy, one wants to rebalance the functioning of these regions. Now the region that becomes underactive is precisely this area that mediates what we call inhibition and cognitive flexibility and affects, as I said previously, the ability to switch between your goal-directed system, which is in another part of the frontal lobe function, and the habit system, which is a bit more primitive and depends more on the striatum, for example.

Chris - If you ask someone who's got this problem and they are getting to the stage where they're washing their hands with bleach, if you say to them, 'Do you think that's a sensible thing to do?' Do they know it's not helpful to do that, but they just can't stop it? Or does the nagging part of them think, 'No, I really am doing some good with this bleach?'

Trevor - That's an interesting question. I think probably both of those in different patients in a sense. So in other words, one patient would say, 'Well of course I know it's stupid to do this, but I just can't help myself.' Another patient might believe perhaps early on in the disorder that it's actually goal directed. But our hypothesis is that there may be a transition from that state to the more compulsive state where you just simply can't control it.

Chris - But why in some people is it contagion on their hands? They're worried about germs, but they're very happy with all other aspects of their life. Whereas another person, they'll be worried about thieves breaking into their house and stealing things. If there's something fundamentally wrong with the wiring in the front part of the brain, shouldn't they have all these problems all the time?

Trevor - I think they do. There's a lot of symptom substitution in OCD. You might start off with somebody who's worried about germs, but then you may show a transition to having checking problems or hoarding problems even. I think these symptoms can be substitutable and I think there's a general tendency to be compulsive, which is expressed in different ways. Now, that's a hypothesis, but I think there's some evidence to support that. It arises from this being a general problem, but why they fixate on particular things initially is probably due to specific experiences. If you are a bit compulsive and you experience the pandemic, for example, you might become focused on germs and that might exaggerate your existing tendency already to be a bit worried about germs. So, I do agree that's an interesting issue: why precisely did you get these particular symptoms? But I think they can generalise to some degree as well.