Please wait while the transcript is being prepared...
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.
