Dr Paul Fletcher, Clare College
Chris - Our next passenger is from Clare College and the Department of Psychiatry, Paul Fletcher. Hi, Paul.
Paul - Hi.
Chris - Welcome to our punt. Iím sorry this was the best we could do. Itís a low-budget programme.
Paul - This is absolutely beautiful, donít worry.
Chris - What is it you work on?
Paul - Iím especially interested in schizophrenia and in particular the key symptoms of schizophrenia which are delusions and hallucinations.
Chris - What do they actually mean?
Paul - They both relate to a very changed experience of the world. An hallucination is when you hear something or see something that isnít really there. A delusion is when you believe something that is quite extraordinary and probably untrue. For example, an hallucination somebody might hear somebody talking to them, criticising them. A delusion they might come to believe their neighbours are trying to poison them or control their actions.
Chris - Do people develop these delusions to explain the funny hallucinations theyíre experiencing then?
Paul - Some people think the experiences are abnormal and the explanation is a perfectly logical one for those experiences. Other people think the experiences are not abnormal but people just reason in very different ways. Other people think itís a bit of both.
Chris - Whatís actually going on in the brain of someone, say, whoís having an hallucination or producing delusions like this?
Paul - We know that people with delusions and hallucinations and other symptoms of schizophrenia have changes in the neurotransmitter, dopamine. We know that it seems to be overactive although itís not entirely clear whether itís the receptors that are oversensitive or thereís too much of the chemical. We know that there are clues that this might be one of the prime suspects. The real thing we donít know is how something as basic and low-level as that can translate into something as complex and human and social as a belief that someoneís trying to harm you.
Chris - Itís interesting because schizophrenia is quite genetic. We know it runs in families but it also tends to come on much late in life even though presumably the genes that cause it are active from the time that youíre conceived. You donít get the disease until your mid-twenties. In some cases a bit later, in some cases your seventies. Whatís going on in the brain to suddenly make this come out when weíre that bit older?
Paul - The mere fact that it doesnít tend to manifest in childhood, although it can, is probably giving us some vital clues about what the key problem is. One possibility is that schizophrenia arises once the brain is fully matured. Itís only at the time that somebody has matured pathways in their brain that theyíre able to experience and express the sorts of symptoms that people with schizophrenia have. Another possibility actually is that schizophrenia is present if you scrutinise closely at an earlier age. In children it manifests in much more simplistic ways: motor abnormalities, speech abnormalities.
Chris - What about the association with various drugs because cannabis has been linked to people getting various psychotic symptoms, if not overt schizophrenia, hasnít it?
Paul - A lot of people are pushing very hard to apply ever greater constraints on the use of cannabis because they believe strongly that it causes psychosis. In actual fact if you look at the evidence we still donít know whether people use cannabis because theyíve got schizophrenia or theyíve got schizophrenia because they use cannabis. One thing we do know is that the proportion of people using cannabis is much greater among people who are mentally ill. Itís certainly the case that that sort of disruption of a brain thatís already vulnerable could precipitate an episode of these unpleasant symptoms.
Chris - If you look at the brains of people who have schizophrenia either with a brain scan or in post-mortem if you look at whole brains do you see any obvious differences with what we would call someone whoís normal?
Paul - Up until the seventies people gave an unequivocal no to that. In the mid-seventies somebody called Eve Johnson in Norfolk Park produced a ground-breaking paper which essentially showed that the ventricles which are fluid-filled spaces in the brain tend to be larger in people with schizophrenia. This suggests that thereís been some degree of shrinkage in the brain. Most psychiatrists would accept that the brain is different in structure. Thereís increasing evidence that it is different in the way it functions.
Chris - Thereís quite an interesting body of knowledge growing now that some of the genes that are associated with schizophrenia are associated with how cells migrate and move in the brain both during development and perhaps during adulthood. We know that we continue to make new brain cells throughout life in certain parts of the brain. Do you think this is something that you grow into? You slowly accumulate enough cells as your brain ages and produce these new neurons that they make these pathways and perhaps connect up the wrong bits of the brains and disclose schizophrenia?
Paul - The very name schizophrenia itself means a splitting of the mind. While many lay people would interpret that as a split personality what it actually means is the different faculties of the brain tend not to integrate with each other. Functional brain imaging, which is what I use to measure whole brain activity in association with a series of challenges and symptoms, thatís seeming to suggest that some of the core abnormalities may be manifest not as a failure to be active but as a failure of different regions to speak to each other.
Chris - Thereís a neurologist who works in Switzerland called Olaf Blanke who I talked to a few years ago. He discovered when he was treating a lady for epilepsy that if he stimulated a certain part of the brain he could produce this out of body experience in this lady. She was effectively experiencing her own body but the symptoms of someone touching that body. She wasnít mapping onto that being her but she was thinking there was another person in the room with her. Do you think thereís a part of the brain that doesnít work properly in schizophrenia which would normally cancel out internally-generated things like voices and other kinds of things and tell you theyíre coming from you and that just doesnít work? People think that theyíre something real.
Paul - Yeah. Thereís good evidence that normally when your or I hopefully speak to ourselves in our mind we actually cancel out the auditory response to that. Itís as though thereís a dampening down. If we hear somebody else speaking then our auditory cortex is very responsive and active. The suggestion is that in hallucinations itís treating internal speech as though itís external. Therefore you hear what you say as though itís somebody else. This would account for many of the phenomena of schizophrenia. There is another very interesting symptom called a delusion of control where somebody feels that their own movements are actually produced by somebody else. The same explanation might hold for this. When I go to generate a movement I know what to expect. I know the outcome of that movement will result in me being in a different position or my hand being in a different position. If I fail to make that prediction then it may be that that comes as a surprise to me. I could then interpret it as somebody else having made the movement. These are interesting speculations and indeed there is growing evidence that this is may be the case. I think Olaf Blankeís work is very interesting in that respect.
Chris - Finally, are we closer to helping people to lead a normal life once theyíre diagnosed with something like schizophrenia?
Paul - I think as we begin to understand the link between a chemical abnormality and a high level expression of a symptom in terms of processes that are very specific like this then we may be in a position to offer newly-targeted therapies. An example of that is weíre now finding we can reproduce some of the symptoms of schizophrenia with a drug called ketamine which has been widely used as an anaesthetic. Maybe if we can target the same receptors that ketamine works on then we can begin to find new treatments, more acceptable treatments for schizophrenia. In fact, only last year a paper came out suggesting that may well be the case.