Welcome to the Oxford University Psychiatry podcast series brought to you today by me, Daniel Moore and I have the pleasure of having Dr Matthew Brew, who's a senior clinical research fellow at the Department of Psychiatry here at Oxford and also a consultant psychiatrist.
Good afternoon, Matthew. Thanks for inviting me. You have a really interesting research portfolio looking at, well, really how to predict potential onset of psychosis in people who are developing it perhaps early in their life. Could you tell us a little bit about that? So this was work that I became involved with back at EU Psychiatry in around 2001. We began developing the first episode of Intervention Services around the same time, the LEO service, early onset service.
And I guess even back then, we were aware, even with very well-designed intervention services, people were still presenting quite late with psychosis, with a long duration of untreated psychosis. The Mental Health Act was being used fairly often and patients were having lost jobs. Relationships fall out of college or school. So we got very interested quite early on in what was called the high risk paradigm. That's the work of colleagues in Melbourne, such as Pat McGorry and Alison Young.
And I guess put in a bit of context, there were sort of two ways to think about the high risk for psychosis at that time. There's a genetic high risk research programme that was led by Chief Johnson and colleagues in Edinburgh, which followed a cohort of people with firstly relatives with schizophrenia. And there was the work, Melbourne, which looked at another high risk group identified by symptoms rather than by genetic risk.
Okay, so you've got a group of people who somehow a high risk of developing psychosis. How do you tell who's who's in the high risk group? You actually do genetic tests on them and then look at their symptoms or so what do the symptoms look like? Okay, so the way we did it. So I guess that is genetic. High risk groups are put to one side and the clinical high risk group is based upon symptoms of psychopathology.
And there are a few different ways of doing that. As I mentioned, we were very much influenced by the Melbourne group. So we used a measure developed by Alison Young called the CALM's, which is the comprehensive assessment of the risk mental state, and asked develop that measure. What I recall initially by retrospective accounts of those with who had developed psychosis, so asking them to give them give her accounts of the earliest experiences they had.
And in addition, she began reviewing the literature on the programme of phase of psychosis. Interestingly, that that work is area was triggered by concerns about a DSM three category of prodromal psychosis, and it's non-specific qualities. So Pat and Alison tried to sort of empirically examine the concept again, afresh, really, and that's what led to the detriment of the cars. There are other measures are very similar.
So colleagues in Yale had a measure called the Six Insults, which also looks at psychotic symptoms in the early stage, and colleagues in Germany to develop measures looking at subtle symptoms of psychosis, which include more cognitive and negative features. But most of UK, Australian and North American psychiatry tends to focus on on using the council. The Sipson stops and tends to focus on what we would call attenuating positive symptoms.
So mild symptoms that look a bit like hallucinations, delusions, things you focus on. So, yeah, thanks. What I'm interested in from reading your research, Matthew, is that you want to have a whole lot of people who have got these sorts of attenuated positive symptoms a little bit like a hallucination, a little bit like a delusion, not quite either of those yet experiencing some unusual sort of features in their life. Perhaps that's not going too well.
But it seems to me that it's very difficult to predict from quite large groups sometimes who is going to go on to develop schizophrenia. And a lot of your work is about how to predict from that large group who is going to develop perhaps a long term severe psychotic illness. So what have we found out, I guess, is a few things to say about that.
I think you've learnt quite a lot. I think the first thing to say is that the original papers from Yemen, McGorry, suggested that people who met these criteria, about 40 percent of people develop psychosis within six to 12 months. That's probably turned out to be not quite so high as that as years have gone by. And what we call the transition data has sort of become less strong.
But saying that a recent analysis by our polling, I think 2012 still was saying that 22 to 35 percent people will transition within two years. So just the measure, as is, is still not so bad at predicting precisely the psychosis within within a couple of years. One in three people will develop psychotic illness. But yes, you're right.
I mean, the reasons why some of the issues I catch myself are very interested in improving their predictive powers and I guess also what's known as a false positive. So misidentifying those as being at risk when that whether or not I can see the big area of psychiatry that this research meshes with is the continuum of psychosis.
So this is the idea that people in the normal population who aren't impaired, aren't seeking, also may have experiences such as ideas of reference, the occasional auditory experience to voice hearing, and they aren't cases or death cases. So you're quite right. And your concern that those you might see in an at risk clinic could be. Remember the general population in their enhanced risk at all.
So we're very much aware of trying to improve the predictive powers of these questionnaires and measures, given this wider epidemiological research in those people who are non help seeking, non distressed and have psychotic type experiences. So you've looked at some really quite subtle psychopathological changes in these individuals to see if they can help predict over and above these tests you might transition. And what have you found out about that? Well, I guess variety of things.
I mean, we were my kind of main role was I led on some serious evaluation delusion formations, and therefore I work in other colleagues such as Oliver has spoken about recently, led on top of that. So we're very interested in. So neuropsychological measures and fMRI correlates predicting psychosis. I guess it's still at the stage where if we don't know how these variables interact to help, you have a clinical tool to be used for defence.
I guess that's a fair thing to say, but I guess there's some things we do now. So I guess certainly demonstrated quite convincingly that's trying to take me, for example, is already elevated in those who might be at risk of psychosis. And the more elevated as people enter the first episode, spatial working memory and so verbal working memory seems to be quite a key feature replicated in several research groups Ireland,
London, Germany, that seem to predict onset psychosis. How do you test of working memory in that study? So what I did was a simple an and back task. So I'm not one of my task looking at people's ability to to relate a stimuli to one that occurred, a certain number of stimuli before. So what you're saying is people are unable to or less good at remembering what's being said to them before having been interrupted with other other things that have been said to them.
And and that that's sort of perhaps that disability or that lack of ability or reduced abilities is potentially predictive of of transition. I think so. So I think certainly that kind of feature in combination with the clinical signs which would make the slightly higher elevated risk, are the things that are important anxiety and depression. So this group, although they don't have a of psychosis, definitely they're at risk.
For one, they will have very likely to have a comorbid DSM diagnosis for anxiety disorder. And again, there's some evidence to suggest I mean, all sorts of reasons, probably because of psychosis, whereas more biological models of these things can increase. Risk treatment also can can can be helpful. Other things you've a work about won't matter. Changes, productivity changes, structural MRI changes, as well as more lifestyle things as a sleep disturbance, substance misuse.
So there's a kind of wide variety of risk factors that are potentially intervene in in this kind of group of people who are high risk. And I guess the challenge clinically is trying to use the least dangerous interventions. Yes, that was my next question, because, OK, so you've got this group of people who are at an increased risk of transitioning into psychosis. How do you feel ethically about potentially giving somebody perhaps a low dose of an antipsychotic in that situation?
To potentially reduce the risk because you might be giving somebody an antipsychotic for no reason at a time in their life where they might be affected by that so. Well, how do you cope with that? That's a really important question. I think when we do debated quite a lot in the early days. So I think empirically, the economy supports at present that it a treatment for at risk to abort the onset of psychosis.
And in practise, some of these patients will have an additional haptics, I think, by far the minority. I think what I recall when I worked in our and our service in South London, it may have been, you know, fewer than 10 percent are the reasons why you might consider it would be because the the patient may have very distressing psychotic experiences, may be very high risk of self-harm or violence, for example. So, yes, I would generally one would be to avoid any psychotic medicine in this group.
You could try out alternative treatments. So I think it's not you might want to consider the use of a view of depression or anxiety disorders as an SSRI or hypnotic, for example, for sleep problems. But I guess the mainstay would be a psychosocial intervention. So psychological treatment and, you know, family work and case management could be very, very powerful because what you don't want to do is to give a treatment to inappropriate somebody who has no risk whatsoever.
Ethically, is really interesting is that the clinics are hoping to develop with this thing a the department is sort of embedded ethical piece of work with the service in the trust to get it kind of slightly difficult interaction directly where what you try and do therapeutically is to normalise the abnormal experience. So quite often when you see a patient, who would you think might be high risk? You trying to do is to alleviate the anxiety because the symptoms are to normalise them.
It's quite, you know, sort of saying what people do hear voices now and again, you may feel feel like a bit of paranoia and look at the emotional charge around to try to lessen that. But at the same time, it's given that normalising message also getting the message. But can I still see you every month for monitoring? So that kind of difficult conversation is hard. So there's a bit of controversy. You may be aware about DSM five and incorporating the attenuated psychosis within that.
The illness seems quite interested in young people's experience of early psychosis services and how the at risk category is used. So we're hoping to embed some quite detailed qualitative research into the clinical services in the future, because that very reason how young people might feel about these diagnoses and terms and acknowledge probability.
And there's discussions within clinical practise. So when we think about early intervention today in the UK, do you think we've made strides forward in knowing who to who to treat and how to treat them? Do you think progress has been made? I think so progress is is bumpy and sometimes goes backwards to get forward. That makes sense. I guess what I what I'm aware of is how naive we were.
I look back to when we set up protocol services 14 years ago, we had this very simplistic view that having this adverse mental state impact on psychosis and we think much more than that. So I guess one of the things that has come out of this research is the adverse mental state described by you and colleagues might be more a marker of general risk for psychiatric illness across the board.
So I think where people are getting interested in is is more general diagnostic view of adolescent young, young adult health. And do these markers predict problems down the line? Americans may end up being psychotic illness. They may end up being personality difficulties, mood disorder, et cetera. So I guess you got a bit more nuanced about that. And that's why in parallel with people being less siloed about diagnostic types and clarity, he generally has been it's been great.
I think it's been a sort of trailblazer for high community care can be delivered an optimistic way. Really focussing on on outcomes are important to young people such as, you know, jobs, education, relationships. I think I'd be very good at that kind of ideological approach. Psychiatry, and I'm one of them is Ed Bradley. I'm very compelled by the argument that he is just doing psychiatry well and it's nothing special.
What I do could do it. Any kind of patient group with any to any diagnostic group, it remains very cost effective way of delivering care. I guess what we have seen the last several years has been a kind of pulling back into the service provision of eEye because of economic cuts. But I certainly feel in this, trust me, more nationally that's beginning to be reversed slightly and go optimistic again, which is good.
Matthew, it's been great to speak to you today. Thank you for your time and a pleasure. I enjoyed your time with.