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Earlier in the week.

And now we'll move on to there's two lectures today

on mental disorders.

Next week, neurological disorders.

And then we'll wrap up with the prefrontal cortex.

Just a reminder, two things.

Keep up looking at the neuroanatomy.

It's quite intensive learning about your anatomy.

So keep doing that training as you go through the

degree module.

And also, please do fill in the have your Say

documents where you can return feedback on the course.

We've had all sorts of interesting issues with the the

videos and lecture cast that we're getting.

They're getting That's good advice, good feedback from my side.

So I'll make a start.

In today's lecture on mental disorders, I'm going to cover

a number of topics.

I'll just change the lights to a little darker, particularly

helpful.

And that's because, you know, maybe a bit better.

Okay, so I'm going to cover the following things.

There's a huge range of disorders to do with the

mind.

These are inner regarding these are these are conditions that

are not got a clear individual neurological cause this lecture.

So next week you hear about neurological disorders where you

can see disruptions, clear disruptions in the brain, circuits giving

rise to it.

There are disruptions in the brain and the disorder results

I could talk about today.

But they're not focal.

They don't part of a particular circuit.

So there are vast range of disorders that come under

mental disorders.

We're going to focus on two in today's lecture.

Post-Traumatic stress disorder and schizophrenia.

That is because there's a lot of research on these

topics in the talk in the domain of brain behaviour.

So if you want to look at how strange behaviour

operates and you're interested in what can go wrong with

the brain, these two studies, we're going to look at

the behaviour and the cognitive phenomenon associated with these conditions.

We'll talk about current thinking in the field around these

disorders, about the neural basis.

And we'll start with post-traumatic stress disorder.

Now, if we were sitting in this lecture theatre in

the blizzard bullets whizzing around and there's a gunfight going

on, you would quite rightly be stressed and you could

be extremely stressed because your life is in threat and

you should rightly be stressed.

It would be good if your body has got a

high level of adrenaline.

If you go back to the electrons stress, you have

that continued response, your heart rate.

So you're able to escape the gunfight.

That is a stress response.

The key word in the disorder here is the stress

disorder.

A disorder related to that is the post traumatic nature

of it.

So if you've got a high heart rate, you're worried

about bullets whizzing around, but you're actually just sitting a

calm lake, having a cup of coffee, relaxing and your

heart rates up, your worry, you are extremely stressed by

that.

Is this post-traumatic stress disorder an example of that process?

So according to the main manual on disorders, DSM five,

they they describe post-traumatic stress disorder as caused by a

situation which of which is which a person witnesses experiences

is confronted by threat, actual or perceived that could do

serious injury or cause death to the person or threat

to the physical integrity of the self or other.

So basically, your thoughts that you're going to die or

someone very close to you was going to die, but

you could you could see or you're going to die,

or you might see your child is going to die

or your parents could somebody extremely close to you would

come under this category.

So it then provokes the response described as an intense

fear, helplessness and horror is what the technical type that

describes post-traumatic stress disorder as.

This is very serious.

It can't just be you had a bad day.

It was pretty bad.

And it has to be something really intense.

The symptoms of the current post-traumatic stress disorder, the recurrent

dreams, recollections of the event or events is often a

sequence of events that can cause these things, but it

can be a single event and the feelings that accompany

the trauma or traumatic event.

And in particular there are flashbacks that occur and these

for this to come under the disorder, these have to

cause intense psychological distress.

So if you experience like so you go to a

party, you say some really stupid things and you keep

going back to that and you can get these.

What happens to me?

I recall some stupid thing I said, I'm not I'm

not planning to recall it.

It just flashes into my head and it is distressing,

but it's not intense and it isn't recurring.

And I'm not like stuck in the moment, can't escape

and thinking about my horrible party.

It's it's I can escape that for people who have

post-traumatic stress disorder, they're sucked up into a world inside

their head of these intense psychological distressing feelings And these

flashbacks And these dreams, recollections of flashbacks can lead to

the person trying to avoid thinking.

Or talking about re-engaging with these events.

And this was not the results of diminished interest in

social activities.

And I don't want to go out typically as much.

They feel detached from other people as they suppress their

emotions because they're trying not to break down.

And this leads to this feeling that the world is

bleak and empty, unfortunately.

So really a brilliant bad disorder to have.

Now, the symptoms that go with this include this difficulty

falling asleep, irritability, outbursts, anger, difficulty keeping, concentration on things

and heightened reactions to things in the world.

So the classic example, one of the things we'll see

in some of the studies is, is war.

So you might say not to be a soldier.

You're sent off to fight in a war.

You're constantly surrounded by gunfire.

The friends get shot.

You get shot.

It's your life is in danger.

And your friends have been killed.

After that, you then associate these soldiers, some of them

a small number of associate the sound short bang noises

with threat to their lives.

And so it could just be a cost of putting

up someone, putting a cup down too heavy on a

table.

These can just set off this stress response in these

individuals that have post-traumatic stress disorder, PTSD, as this description

indicates, it really does need to have to had mental

health functioning so that they're not keeping themselves in good,

well, mental states, but they also have poor physical state.

If you're not sleeping very well, then if you've experienced

that prolonged lack of sleep through stress or whatever else

can cause that noisy neighbours, you end up feeling rundown,

your immune system lowers.

These are all things that happen.

But one of the factors we start to go into

this beyond the symptoms is that men on average are

exposed to more stressful events.

There's more at least currently these things are changing.

There are more men in the military movement.

It's now up to police officers, fire workers, etc..

And so they tend to be exposed.

But for some reason, women tend to generate end up

generating more cases of PTSD than men.

They may and it's difficult to say there's a paper

on this, but it may be the way women on

average.

This is a really important thing about gender differences, about

the way perceptions of threat occur.

And there are things that one of the one of

the common things that can cause PTSD is childbirth, which,

of course, is a female specific thing.

So the gender of women who are going to have

babies is very stressful events and it can cause lots

of threat to your life and the baby you're trying

to give birth to.

So the evidence from the research suggests using twin studies.

If they look at twins and non twins, they can

see that if one child in a twin identical twins

experiences PTSD, two events is very likely, the other one

will.

Also, it's not very late is a higher likelihood.

The other twin also reacts with PTSD to traumatic events.

So they've shown that there are some genetic susceptibilities towards

PTSD.

This is not surprising, and I think you should take

this as true of almost every behaviour you express that

there's likely to be some genetic loading that leads to

it.

And you know, the your body is built by genetics,

but the environment influences the last couple of aspects of

you.

And PTSD is one of those things, you know, they

influence not just the likelihood that someone will develop PTSD,

but their exposure.

So this comes under there will be just certain genetic

factors that make some people take more risks than others.

I haven't chosen to go into the military.

It's a bit too risky for me and it's not

something I want to do.

But for other people, the idea of being in a

war zone is an attractive life possibility.

And that puts them at greater risk.

There is definitely there's a number of criteria.

People have worked over lots of research over the years

about what can cause PTSD.

So getting a traumatic event earlier in life, for example,

suffering, being early in life is more likely to lead

to PTSD than suffering abuse later in life.

Exposure to repeated events like that, that's going to lead

to more likelihood of PTSD.

And we'll come to a dramatic example of that.

Suddenly having a depressive father has been found to be

a risk factor.

Is it clear from that one of those bits of

data where depressive mothers don't have such an impact, depressive

fathers do?

That could well be that the data that's available increases

in education allow you to be less likely to have

PTSD, if you will, low level of education.

So doing a degree and doing a degree still is

somewhat protective of reducing your PTSD risk.

It seems to have social support.

This goes back to lecture on stress.

You remember the mothers who were licking their pups and

taking care of them better and having a social access

to other animals.

We see this in humans as well, and surprisingly, the

people who don't have to get social support are more

likely to develop these topics.

It also, unsurprisingly, does not help if you have generalised

anxiety disorder, panic disorder or depressive disorders.

These are other mental health conditions that put you at

greater risk if you experience a traumatic event.

So few studies have identified specific genes that are possible

risk factors.

Unsurprisingly, these things go back to the lecture on stress

and reinforcement.

You can see that the serotonin receptors and the dopamine

receptors a really key important features for that association.

So if you for example, one classic example of a

study on PTSD was a ship went down or boats

in the River Thames, a number of people died in

the incident.

Several people survived that.

They felt they had post-traumatic stress disorder.

Watching people drown in front of them now that that

exposure to that, the person has to band together, that

experience of seeing that person's hands slip out of their

ears and drown in the water.

Now, their dopamine system and the serotonin system are an

important regulation of the processes in which they can bind

that information to their memory.

So what the research has shown is that genetic genetic

dispositions come from those circuits.

And as you noted, it's not just if you have

the right genes, you'll get PTSD.

It's utterly the environment that will influence that.

Now, this is a dramatic example from 2010.

So 12 years ago, some impressive researchers, Calasso and colleagues

studied survivors of the Rwandan genocide.

This was a really awful genocide where one group, one,

one and one particular cultural grouping of people in Rwanda

massacred another group of individuals in the exclusion of Hutus.

Unfortunately, what that team were able to do is look

at the survivors who survived these events.

And what made it actually dramatic was that they were

hacking people to death with machetes so that people were

seeing loved ones killed, but also by their neighbours.

So all of these things made it extra traumatic.

And this graph they developed from the data.

So this is of Carlson and Birkin's book, which you

can as one of the core textbooks here.

So what you have on the y axis is the

frequency of PTSD.

And on the x axis is the number of traumatic

events people experience.

So we'll have a group of people down here who

experience no traumatic events, and they had no PTSD, no

surprise whatsoever.

And then you can have people who experience maybe one

event but have no PTSD.

But then you have a group of experience, three events.

And for people, it's been three events.

They found there's a kind of 35% who have PTSD

and higher than none.

The increase in the number of traumatic events they experienced

this could be seeing their family members hacked to death

or seeing people burned or were shot all sorts of

ways in which horrific events occurred in that incident.

As you go up to over 20 events, there wasn't

a single person after 20 events who didn't have PTSD

from observing these.

So what this graph is showing us is that the

more events, the one experience is, the higher probability you

will develop PTSD.

There's pretty clear evidence.

It can be one shot.

It doesn't show in this graph.

But like I said, if you were to lose your

partner or your parent and they slip out of your

hands in a boat disaster, you would feel this intense

guilt and that that could be a factor driving over.

But on average, this graph tells us that story.

Now, this is this is a redrawing of a diagram

you saw in the stress lecture.

You remember that we talked about this pathway, the D

axis and the hippocampus is critical for stress.

So what people have done, and I mentioned in that

stress fracture, we're coming back to that, the work that

was done to look at using MRI, genetic resonance imaging.

And you heard the lectures earlier in the course and

how this worked.

And they were able to look at combat related so

back into the war, post-traumatic stress disorder.

So veterans who had been at war come back, have

their brains measured.

Those veterans who had PTSD compared to veterans who didn't

tended to have a smaller hippocampus.

And they described that as hippocampal damage to something smaller

in their head.

The campus.

And in fact, one study found that that was reduced

by 20%.

And critically, the evidence they provided wasn't just that, oh,

they have a smaller hippocampus, but more exposure to combat

as a veterans.

So the more that person had experienced combat in Iraq

war in this case, I think it was or maybe

it was either the Vietnam War with Iraq war.

It's an American study.

The more the smaller their hippocampus would end up.

And that goes back to the stress lecture.

We talked about work with primates where we could look

at studying macaque monkeys or rats.

How you do stress experimentally, it can damage the hippocampus.

So we see that occurring in post-traumatic stress disorder.

And another study listed here that police officers also went

on to or did not go on to have PTSD.

So, again, this is all building a picture that PTSD

will tend to lead to a smaller effect.

Campus in 2002 was a very interesting study published in

Nature Neuroscience by Gilbert Stephens studies, who argue that at

least part of the reduction may pre-date the exposure to

the stress.

And I mentioned before that certain genetic factors will predispose

you to go into risky situations more than others, and

that will lead you to potentially end up with PTSD

more than others.

What they found remarkably was that the smaller hippocampus may

be a previous predisposing factor for the acquisition.

So what they did, and this is just an incredible

study they've managed to track down.

I don't know how they did this because it's very

difficult for two pairs of identical twins once they got

it.

Twins were only one of the two went to the

Vietnam War and the other one did not.

They were able to scan those and almost half of

the men just let you take a group of 40

people.

Half of these men went on to get PTSD and

half didn't get full.

You have three groups that people who didn't or the

people who didn't get PTSD, people who went and people

to people who went and got PTSD, people who didn't

get PTSD, and the twins who stayed at home.

So the people who had been exposed to the trauma

developed PTSD.

Unsurprisingly, as more have the combine than the people who

did not develop PTSD in that twin group matching the

past studies.

But and indeed, the smaller the hippocampus, the more severe

the PTSD providing that link.

But the really surprising thing was that the brothers, the

Monozygotic twins, didn't go and also had a smaller hippocampus,

which is really weird is this By at a distance,

the hippocampus have been shrunk by news that that brother

had gone through war.

That is not what what the scientists argued.

Rather, they argued that maybe having a smaller hippocampus gives

you less capability to deal with the stressful situation.

It's not harming you as well, and you are more

likely to go on.

This is all about likelihoods, not about this is not

a deterministic.

If you have a small hippocampus, you will get this.

Not at all.

It's more like a predisposition.

So what you have from this story is really the

case that the hippocampus in your brain that you process

in your life of development for you through your genetics

and your exposure.

Growing up grows in a certain size.

It will it will not cause you to be at

risk of PTSD.

If you do suffer PTSD, it will have a knock

on effect and actually also reduce the size.

So there's multiple factors at play there.

So that's the key story.

Comments in literature.

But let's turn to another key brain area in Sam

Solomon's lecture on emotions.

You've heard all about the amygdala and it being critical

for fear.

And what I've described at the beginning of this is

somebody sitting by a lake and feeling about bullets whizzing

around and they're having a really threatened fear.

They're in fear, but there's nothing actually happening.

So the several studies have found that the amygdala well,

is is is is showing these when these when they

look at people lying in a scanner and they look

at how they're reacting to stimuli, food reacting to to

the to the for their symptoms, they can see increased

activity and the link to that.

They've also looked into the prefrontal cortex, as you'll hear

next week is a is a brain area critical for

regulating our behaviour.

We heard early in the course of the lecture one

of us and this gauge who couldn't regulate his behaviour

after Paul was blowing through the front of his head.

So there's a, there's a clear long history going back

to early 1900 on the role of the PTSD in

regulating this.

Clearly sitting at a lake and worrying about bullets flying

around, whether or not there is a failure to regulate

your your emotion.

And so what's argued by colleagues Ralston and Phelps in

the key paper is that the people who've developed PTSD

are lacking that that that controls in their prefrontal cortex

to their amygdala.

They're unable to dampen down the responses in the amygdala.

It's a bit like if you experienced some stressful event

and you could keep ruminating over it and keep thinking

about it and your heart rate will keep going up.

Or you can sit and rationally think, that wasn't that

bad.

It's okay, I'm still here.

Things are going to be alright.

You talk to your friends and you're not worrying about

it.

Why are you worrying about this?

And you have that whole dialogue that is your prefrontal

cortex at work working to lower your your stress response

to make it look So that's wrong.

And me giving a narrative about you talking to your

friends.

What we're showing now is data from a key imaging

study by this team and colleagues, which is that this

helps that.

So this helps as a key researcher in this area

and in the US.

So what they did was take this is a graph,

here's the on the y axis going up and down

is the amount of estimate reactivation.

So if you have a high response, it means this

area is highly active.

Here at point eight or zero, there's no activity.

And compared to baseline, I'm going can look at the

data from just two areas and I'm going to show

you the whole break.

We're just going to average the activity in either the

amygdala or we're going to average activity in the medial

prefrontal cortex.

These two areas have been talking about and what they

did in this study was just to show people with

PTSD or not PTSD lying in this scanner, these two

groups faces happy faces or fearful faces.

And what they found was that the amygdala in people

with PTSD shows a much higher reactivity.

It's more reactive to faces in general, but the favourable

faces are driving more activity in these people, whereas in

fact the fearful faces drive less frontal activity compared to

control participants.

Just is sort of crossover.

This is real data, so it's not as neat as

you would want from an absolute textbook story here.

It's like why is there no response in controls and

why do they switch?

There's not a good explanation for these exact patterns.

The key conclusion, the expansion in colleagues and then has

been following through the field is that with PTSD there's

an increased response of reactivity in the amygdala driving reactions

and less less exerting control from the free prefrontal cortex

in PTSD to dampen that.

So why?

What's going on?

That's okay.

That's that's two brain areas.

Things that in very simple, if you go back to

2001, AI central theory was put forward by Chris Bruin

at UCLA that has really dominated this article and the

one following it had 4000 citations.

It's a really, really influential idea to bring that forward.

So Chris Bruin is the I was thinking about why

is that?

What is going on when people have flashbacks or not

flashbacks?

And he argued back in 2001 that a lot of

what we do but I just described earlier talking to

a friend of mine, a stressful experience is that you

might go back into it and think about that memory.

It'll be some cue.

It could be a picture from the party, or often

he describes it as verbal.

You might talk about it, talk about something and the

cue of the party, the embarrassing party then drives recall

going, Oh yeah, I remember the party.

You were there.

It was really embarrassing.

That's happened.

What he describes at the bottom here is that sensory

input going into your brain is this cue party.

Last week's party course is a complete recall.

See, it happens.

All of the memory is verbal access, memory systems, standard

operating system in your brain.

And you don't really get there because you remember the

party.

It's all contextualised.

You know who was there.

You can recall it.

There's also at the same time, the sensory access memory.

You get the sensory information about who was standing where,

what the colour of the party was, and was it

what was going on in the party visually in your

mind's eye.

But that's what he argued was the typical kind of

you don't really you can inhibit the fear system in

that sense.

Why argue that the flashbacks occur when you can't?

The participants get a sensory input and this pathways weakens.

They're not able to recall the the memories through a

verbal description is not sufficiently and there's a strengthening of

the pathway through the sensory access memory.

And so, for example, people who have road traffic accidents

is another classic PTSD that nearly died.

They had an awful crash.

They had maybe all their limbs are broken.

They're in hospital for months that whenever they smell petrol,

it causes a flashback to that horrific crash.

And in that scenario, this flashback is the smell of

petrol driving this memory and activating the fear system.

And that was a theory put forward in in 2001.

It was then updated is when he collaborated with new

versions that use the two other colleagues in again, a

very influential psychological review article where they essentially invited a

lot more boxes to the is one of the first

things to say anything that more boxes they've now added

a lot of brain areas to to sketch out what

exactly is this mean in terms of the brain and

the replaced the idea of the sound system, the verbal

and non-verbal systems with the idea that some memories you

have contextual memory.

So the context is a broad word, but if I

say to me the past and you say, Yes, I

know that was a policy, or you might say for

the party, yeah, you was there was in my friend's

house and we had drinks and there was the, there

was a big noise and everyone had to leave.

And that's contextual memory.

You remember the house, you remember who was there.

It's not, you know, these are all the details that

can be drawn up from the contextual representations and sensory

representations.

It's what was the colour in the party, what was

the drink, what was the if you had a juice?

What was the colour of the juice you were drinking

at the party?

What was the smell in the party line?

All these sensory experiences would be processed by your brain.

So what the idea, if we start at the top

here, is that in normal recall remembering that party, you

have this top down.

If you start in the right, that prefrontal cortex is

processing the verbal information or the pictures or whatever it

is, it reaches your prefrontal cortex to allocate the decision

that you're going to go in and recall this party.

And you then you can see there are three arrows

coming out.

You start to derive a whole range of brain areas

critically, including the hippocampus.

So if you don't have that hippocampus module in there,

it's been caused by surgical removal bank slices for whatever

would come up under the amnesia lecture recovery, you won't

be able to complete the circuit and retrieve the memory.

It will be incomplete.

But there's a range of areas you don't need to

worry about the full detail in this, in this circuit.

But the core idea is that you can at the

end of that, you get this visual imagery, you can

you can see in your mind's eye or you can

describe that some people don't pick on imagery.

They can describe what was happening at the party.

But there's also a pathway down here that's, you know,

that can be activated.

This to do with the sensory features of the past

involving the amygdala.

Was it a positive party?

How did it feel?

The intercepted parts of the interception?

It's about your body's feeling in you, feeling hot, you

feeling irritable.

All sorts of aspects of this would be under the

insula.

Okay, that's normal.

Let's imagine.

This was this was a gunfight.

Breaks out at the party and it is your life

was in threat.

You survive the people that shot and die.

Now, when you later hear a noise like a car

backfiring, what they've argued is that this kind of situation

or cue a loud noise, doesn't go through the prefrontal

cortex.

It goes straight through early sensory cortex, through your auditory

cortex, in the case of noise.

But it could be through your visual cortex for a

picture that could stimulate you to remember the party.

And you get this rapid.

All these red areas are activated directly without any control,

and you do not remember the details in the same

way you flooded by images and sounds.

So this this description comes from the idea that when

people remember that gunfight in the party, they can't walk

their way through it in the way you would describe

because you've been to that just flooded by sounds, pictures,

images in a quite fragmented way.

And this model tries to explain why that occurs.

So in summary, there are symptoms that occur occurring in

dreams that could move on into the next topic the

recurrent dreams, recollections of traumatic events, feelings of of hopelessness

and so on.

Intense psychological distress occur.

There are genetic environmental factors that lead to people acquiring

PTSD.

Hippocampal size may be a risk factor being smaller or

being bad, and a dominant view is that traumatic events

that they don't tend to get contextually bound together when

they're encoded or learned and become associated with that kind

of sensory reactivation pattern.

So so one of the features out of this treatment

is trying to allow people to go back and find

re-exposed to to reconsider in a more contextual way.

The events, normal retrieval occurs through this top down process

of directing your attention to a memory.

Flashbacks occur by a bottom up, sensory driven process.

So this is some of the key takeaway messages in

what we're covering on PTSD.

I'm now going to move to the second part, second

part of this lecture on schizophrenia.

So this is a serious mental health disorder affects 1%.

The cost to society is enormous.

This exceeds all counsellors.

Descriptions of the symptoms go back to ancient times, really

long time back to ancient Greeks and there's a movie

that I recommend you watch about a patient called Gerald.

Gerald in the movie is interviewed.

He's constantly twisting his hair.

He describes when when asked, How are you?

How are you doing?

He talks about sperms and eggs and nuclear fusion and

then said, Just how does that make you feel?

And he says, Well, the painting on the wall has

a headache.

It's really covers all the different features of schizophrenia.

But so do go and watch this movie.

We don't have time not to actually watch it.

But what Gerald highlights in one individual case and it's

important to recognise that's unusual.

Normally patients with schizophrenia have a number of symptoms, but

not all of them that the symptoms are categorised into

positive ones, negative ones and cognitive ones going back to

2004.

So it's a very serious mental disorder.

There are thought disorders, delusions, hallucinations, bizarre behaviours that in

the movies world is constantly.

Twisting his hair all the way through the movie.

It's not a normal behaviour.

It's a feature that occurs in schizophrenia.

So positive symptoms are not good things.

It's a bit of a misleading term.

Positive symptoms are symptoms the patients express to make themselves

known the evidence, the presence.

So people don't normally have these.

So these include delusions, hallucinations and thought disorders.

So we look at thought disorders.

This is basically that Gerald, when asked in the movie,

how are you feeling?

And he says, well, that picture has a headache.

That is not a rational response to the question.

Or if you go to listen to the movie of

Gerald, everything he says contains perfect syntax and grammar.

There.

There's no words he's made up.

It's all real words put together.

It sounds like it's incredible, but it's disorganised.

It isn't.

It isn't coordinated.

The ideas jump from one topic to another.

They go off on a complete tangent.

So it's very difficult for the patient to cope with

life if that's how the brain operates, that they're disorganised

and it's very difficult for people to care for them

and look after.

If they have this severe schizophrenia and they think rational

things about it, they can talk about what is the

point?

Why does the picture of will have a headache?

And they really have a hard time organising their thoughts

and logically sorting out what's plausible that could have happened

and not plausible and absurd.

And they jump from one topic to another.

Sometimes they use meaningless words.

They can move off.

But as you hear Gerald, it's they slip these in

here or there.

And sometimes the conversation and just choose the next word

because it rhymes rather than it being the most appropriate

one.

That's the disordered thought.

The delusions are fascinating and schizophrenia.

So these are things that are contrary to facts.

So my wife previously is a clinical psychologist and worked

with schizophrenic patients in hospital.

And one day she was talking to a man saying

he's later that afternoon going to travel to Bath from

London.

And it's very late in the day.

And he's he's locked in for his safety there.

And she said, how are you going to get to

bars?

And he looked at her as if she was completely

crazy and said, why, of course.

They started beating his hands up and down.

And she slipped.

This is quite a common occurrence that this belief is

not only that they are deluded, but they think he

believes he can fly and used to say, how are

you going to fly and change the conversation and move

on.

But this is one key example.

I remember an experience I had talking to someone.

So there are different types of delusions that delusion that

patient had was a delusion of grandeur.

He believed he could fly or had a special magical

power.

There are delusions of persecution, and these are these are

the thing that makes schizophrenia quite dark and a very

unpleasant disorder to have.

So the real classic problem in schizophrenia is belief that

they're being plotted against or somebody or a group of

people are conspiring against them.

So if you're in the UK, it's very likely they

start to believe that it's all either of them.

If you were in the US, they will be the

FBI.

If you go back to the ancient Greeks as written

in text, it'll be whoever the bogeyman or whoever, the

secret people that are in charge of of society, you

know, the guards in the tower, whoever it is.

Delusions of grandeur are like this belief.

They can fly to the channel to remarkable things or

have special godlike powers is a classic example that no

one else has.

But they have these powers.

One of the other unpleasant features is schizophrenia, delusions of

control.

They believe that they are being controlled by others, forced

to do the bidding of someone else and often believe

that there's an implant in their head.

Something's got inside them that's causing them to do it.

If you go and watch the movie of Gerald's, you

see, he feels like voices in his head are telling

him to hurt people, making him do unpleasant things.

And they said, Do you want to do these things?

And he says, No, I don't want to hurt people.

But the voices commanding me to do it.

And it's hard.

So that takes me on to the third symptom is

just hallucinations.

These are often auditory.

They can be visual.

They might see things that aren't there, but often the

auditory.

And very often they involve voices of somebody talking to

them inside their head.

So if you've ever seen the film A Beautiful Mind,

it explores that whole idea of Russell Crowe as the

actor in a film of a voice of a person

who is really present to the actor.

That situation in the film.

And it's highly disruptive because the person can tell them

to do things that aren't out there.

That's all positive, but not particularly nice symptoms.

Negative symptoms occur that are taking away things from the

person.

So these include and include things like what an emotional

response he'll see.

If you watch Gerald, he's just looks really dumb.

He's very he looks tired.

It doesn't look very happy.

He doesn't look very well.

So, you know, people don't speak as much of schizophrenia.

They don't initiate things.

They persist on things they shouldn't.

And they show this effort to anhedonia, but they can't

really take much pleasure from things like a really great,

great food or a lovely meal.

They just can't they don't tend to be as excited

by it.

And that partly leads to the other symptoms lead to

social withdrawal, which is not a good thing for them,

for their well-being.

There are negative effects as well.

So this causes this lack of affect to reduce motivation

in the negative symptoms.

Cognitive symptoms are also things that are lost, so they're

also negative in that sense, but they're specifically not to

do with the emotional well-being.

They're to do with things like IQ.

So sustaining attention, learning of memory, abstract thinking and problem

solving that all get disrupted.

We'll see in a moment the key areas of the

brain for learning and memory and problem solving of the

hippocampus, the medial temporal lobe in the frontal cortex, which

are disrupted in schizophrenia.

So these symptoms don't just appear overnight.

It's not like you suddenly wake up like, you know,

through neurosurgery and suddenly you lose these things.

They come in over 3 to 5 years.

Negative symptoms occur first, then the positive, then the cognitive,

and then the positive ones become florid at the end.

Pharmacological evidence.

So we're going to.

Journey.

Now, there's been a long story in the literature going

back decades about the idea that dopamine might be the

key molecule that is disrupted in schizophrenia.

The dopamine hypothesis, which is no longer thought to be

true, as we'll see, but is still the still very

good evidence that dopamine is involved in schizophrenia, but that

it's the sole pathway is not.

This came around from the mid not the 1950s.

This particular man took a drug that was being used,

the surgical shot and applied it to other disorders of

mood and found schizophrenia.

This compound proved chlorpromazine actually was quite effective at helping

treat some of the symptoms in schizophrenia.

And he's tried it on a range of different disorders

and it became a first line treatment for schizophrenia fighting,

particularly this psychotic, which is these hallucinations and delusions.

So is not very effective at certain aspects of features

of it.

But it did.

Dramatic benefits for schizophrenia changes.

Their attitudes, hallucinations and delusions are diminished somewhat with this

drug.

But it has lots of corrosive side effects.

And therefore, a number of medications have been developed since

that time.

All of them had a similar compound feature in common.

They block the antagonise.

They just they antagonise these dopamine receptors than normally the

ones involved in that reinforcement process.

Now, another group of drugs that have the opposite effect,

they agonise, they increase the response of these these these

responses.

And these are things like amphetamine, cocaine.

And you remember my lecture on reinforcement learning and the

rate of these increase dopamine responses.

So in that case, these drugs can you know, if

you take a schizophrenic, if you give them cocaine, they

will have higher schizophrenic experiences, worse than worse than their

their experience.

Drug taking is a real problem in schizophrenia.

So really impressive.

Again, this is like one of these heroic studies.

And you think that this group, by the rule managed

to to put by intravenous injection a group of schizophrenic

patients and control participants in and out in a scanner

and monitor the amount of dopamine released in the striatum

using positron emission tomography.

And they found that in Fetterman caused more dopamine release

in the striatum of schizophrenic patients compared to criminal subjects.

So what we're seeing in this graph here is the

amount of dopamine release.

And you can see here this is controls being given.

Amphetamine is just like the rats in the lecture previously

on Striatum.

They're increasing their dopamine on most of them.

But schizophrenics don't have a higher response.

And the key thing you're taking from this graph is

that, okay, so they have a higher response.

But impressively, the greater the response of this person up

here has a really high response.

And there on this graph over here, the more they

have this response, the mean, the more the positive symptoms

are expressed during the scan, the more the hearing voices

having having hallucinations.

So an impressive link.

But of course, the small samples are very hard work

to do.

Okay.

Another possibility that's been explored is that the dope receptors

are changed in schizophrenic patients.

So this is not that they're releasing more of me,

but their receptors are are are changed.

And that's because the drugs work by blocking those receptors.

So the researchers and performed an analysis of post-mortem brains.

They got hold of schizophrenics, brains and looked at them.

They also use positron emission tomography to look at this

late radioactive ligands.

And they can make radioactive dopamine and explore responses to

the amount of dopamine released.

And in reviews, they concluded, this story doesn't stack up

so well.

There's only a modest increase in the different receptors in

schizophrenics.

And it seems unlikely that this is the primary cause

of the disorder.

It's the other structures occur in the brain that are

just moving so we can get get through the lecture.

So they're in when they do neuropsychological testing and brain

imaging studies, they can see that there are these changes

in the problems of moving and memory.

And unsurprisingly, this could be linked to the frontal lobes

in the hippocampus.

That's that's stating what we know from the amnesia lectures

and a reduction in the brain volume is occurs in

these schizophrenic patients because these highlighted brain areas but much