The neurobiology of psychosis: past, present, future

Published on April 30, 2024   28 min

A selection of talks on Neurology

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0:00
Hello and thank you. I'm delighted to have the opportunity today to be discussing what I really think is one of the most interesting scientific questions available to us today and that's what it is that's occurring in the brains of individuals that are experiencing psychosis. What is it that could be going on to really bring a whole new world into being?
0:27
So, I think to understand where we are today, our understanding of the biology of psychotic disorders, we also have to think about where we've come from. So, I'm going to start with really the dawning of the era of modern psychopharmacology, which still provides much of the foundations for our current understanding of psychotic disorders. I'll then be moving on to think about non-dopaminergic mechanisms that contribute to psychosis and finally, thinking about what this means for both our current treatments and for treatments on the horizon.
1:04
So, the earliest dopamine modulator had been used for the treatment of psychosis for centuries in India. It was also used as our general tranquilizer, wasn't until the middle of the 20th century that its active ingredient reserpine was isolated, but its use in psychiatry was really overshadowed by scientific findings that occurred in France around the same time.
1:32
So, the real discovery of the first modern antipsychotic occurred thanks to work by the anaesthetics department, particularly the anaesthetist Henri Laborit. The anesthetists at this time had realized that a lot of the morbidity and mortality that they were experiencing during surgeries arose as a result of the insults of surgery specifically, but rather the body's reaction to those insults there was the often overactive stress response that could harm more than help and so the anesthetists thought, well, how could we dampen this down? What they wanted was something they termed a 'vegetative stabiliser', something to try and stabilise the nervous system. They experimented with a variety of compounds, but they found the most powerful to be compound initially termed 4560 RP, later known to the world as chlorpromazine. What they found was, first of all, it did that job very well, but also, there was an interesting occasion when this drug was used in surgeries where the patients remained awake. For instance, in rhinoplasty. This would typically be a rather unpleasant operation. As you can imagine, it would be quite anxiety-provoking for the patient to be awake whilst they were having their face operated on and patients would tend to be very distressed during the operation. The anesthetists noticed that when the patients were given 4560 RR they had this indifference to the world around them. They weren't really sedated, but they weren't stressed or agitated by circumstances that you know would be quite stressful and agitating to most of us. They said, well, this may be of interest to our psychiatric colleagues. It took a little bit of time, but then Pierre Deniker and Jean Delay decided to use this compound in psychotic patients, and they found that this was very effective and it was different from the existing pharmacological treatments because it was more than just a sedative, something that would send patients to sleep. It didn't seem to sedate, but it seemed to dampen down psychotic symptoms and make patients within the lock wards easier to manage. It then followed many years of bickering about who should get credit, which will be familiar to anyone working in scientific research still nowadays. That was really one of the first bits of the puzzle and really thinking about psychosis from a biological angle.

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The neurobiology of psychosis: past, present, future

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