Dopamine Hypothesis for SZ (NT) (BIO)

Question 1

Dopamine Hypothesis SZ

Dopamine

Answer 1

Don’t mean is an excitatory neurotransmitter that’s main function is to give a feeling of pleasure

It’s known as the pleasure neurotransmitter because of this

It is also responsible for addiction, motivation and movement

Involved in the reward pathway and is responsible for rewarding related behavior

Question 2

Dopamine Hypothesis SZ

Glutamate

Answer 2

Glutamate is a neurotransmitter that regulates dopamine and serotonin levels

It is involved in memory, learning

It is the most common neurotransmitter

It regulates the development and also the creation of nerve cell contacts

Question 3

Dopamine Hypothesis SZ

GABA

Answer 3

Gaba is a neurotransmitter that’s purpose is to inhibit dopamine

Question 4

Dopamine Hypothesis SZ

seritonin and dope

Answer 4

Decrease levels of serotonin may lead to increase levels of dopamine and vice versa

As when one of them is overproduced then the other will be under produce

This does not happen when they are both over produced or underproduced at the same amount only when there is an imbalance

Question 5

Dopamine Hypothesis SZ

neuron NT recap

Answer 5

First the action potential electrical impulse enters the axon terminal

and burst the vesicles releasing neurotransmitters that travel over the synapse

then they are received by specialist receptors that are specially designed for receiving them in paticular

and then the neurotransmitter can carry out its function

if they are not used by a receptor then they are reuptaking by the axon terminal they’ve just been released from and recycle for use

Question 6

Dopamine Hypothesis SZ

basic overview of the og dope hypothesis

Answer 6

The Dopamine hypothesis, a biochemical explanation of schizophrenia,

suggests that an excess of the neurotransmitter dopamine maybe responsible for schizophrenia

Question 7

Dopamine Hypothesis SZ

how did it start

Answer 7

During early research it was found patients who abused large doses of the drug anphetamine

which mimics the action of dopamine in the brain

often showed the positive symptoms of psychosis such as hallucinations and delusions

therefore a link between high dopamine levels and schizophrenia was established

Question 8

Dopamine Hypothesis SZ

lieberman et al 1987 +

Answer 8

States that 75% of patients with schizophrenia

show new symptomns or an increase in psychosis

after taking drugs like amphetamine and methylphenidate which mimics the action of dopamine in the brain

Providing evidence for the links between schizophrenia and high levels of dopamine

Question 9

Dopamine Hypothesis SZ

Hyperdopaminergia

Answer 9

in the 1950s 2 antipsychotic drugs chlorpromazine and reserpine

were found to help reduce the symptoms of schizophrenia

however both cause tremors and muscle rigidity which is symptoms of Parkinson’s Disease which is caused by Low levels of dopamine

it is therefore argued with schizophrenia maybe caused by high levels of dopamine (Falkai et al 1998 +)

There are two exclamations of why this may occur

1) low levels of beta-hydroxylase which is an enzyme that breaks down dopamine

2) D2 dopamine receptors may be hypersensitive in the presence of the neurotransmitter

or there are simply more D2 receptors on the postsynaptic cells
( so they send a message to get more dopamine to fill these so there is excess opening of what is actually needed)

Hyperdopamogenia causes positive symptoms when it is present in the mesolubic pathway which is in the limbic system

Question 10

Dopamine Hypothesis SZ

Hyperdopaminergia in the Mesolimbic pathway

Answer 10

Hyperdopaminergia in the meadowlandic pathway causes the positive symptoms of schizophrenia

The mesolimbic pathway consists of the limbic system including the amygdala, hyperfamous, Hippocampus and the pituitary gland

When me a pleasure stimulus is experienced this pathway is activated and the nucleus releases dopamine

Is also activates the emotional and learning circuits

This is linking that pleasure stimulus of positive feelings to the positive symptoms of schizophrenia as excess dopamine has been released

This also makes sense as drugs and enjoyable habit forming activities also triggers this pathways activity

which is therefore also linked to dopamine and positive symptoms of schizophrenia

When a pleasured stimulus is experienced the nucleus releases dopamine and also triggers the emotional and learning circuits to activate as well

If there is an excess amount of dopamine present in this pathway positive schizophrenic symptoms will be experienced

Question 11

Dopamine Hypothesis SZ

Hypodopamingeria in the mesocortical pathway

Answer 11

Hypodopaminergia is V lack of dopamogenic activity this causes negative systems when in the messocortical pathway

The messocortical pathway is associated with the PFC and other outer brain lobes and as linked to reward seeking and motivational behaviors and emotions

A lack of normal organisation, cognative deficiencies and a lack of motivation

all lead to the negative symptoms of schizophrenia

which is all due to a reduced amount of dopamine in this pathway

Question 12

Dopamine Hypothesis SZ

Serotonin and negative symptoms

Answer 12

Closer pain and antipsychotic drug binds to D1 and D4 doping receptors but only weekly to D2 receptors

as a clozapine binds to serotonin receptors as well

And it also reduces both positive and negative symptoms of schizophrenia

It may be that irregular Seritonergic activity causes schizophrenia

However serotonin does regulate dopamine levels in area such as the mesolendic pathway

So it might not

Question 13

Dopamine Hypothesis SZ

Howes and Kapur 2009

Answer 13

Howrmes and Kapur (2009)

Made a more recent version of the doping hypothesis which suggests that dopamine disregulation in the Straitum is the common cause to psychosis

these researchers suggest that attention should be paid to High presynaptic dopamine as opposed to irregularities of dopamine receptors

they focus on interactions between genetic, environmental and socio-cultural factors

and believe that the dopamine hypothesis should be softened

and viewed as an explanation to psychosis proneness rather than explanation of schizophrenia

Therefore this explanation is considered more holistic as there are more individual factors that can affect whether or not a person’s protocytosis

and this also suggests that high pre-synaptic dopamine in terms of doping regulation causes psychosis

rather than irregularities in dopamine receptors

Question 14

Dopamine Hypothesis SZ

another origin story

Answer 14

In the 1950s antipsychotic drugs were used to lower the levels of dopamine

found it also lowered the levels of positive symptoms such as a hallucinations

but increase the levels of negative symptoms such as motor movement dysfunctions similar to Parkinson’s Disease

so it was therefore argued that schizophrenia was caused by excess levels of dopamine

Question 15

Dopamine Hypothesis SZ

Tenn et al 2003 + and Animal research

Answer 15

• tenn et al 2003

• gave Rats 9 amphetamine injections in three weeks

• and found that they have schizophrenic-like symptoms such as stereotypical movements and social withdrawal

– and dopamine agonists were effective at reversing these effects

• it demonstrates amphetamine which increases dopamine levels caused schizophrenic symptoms

• and an antagonist that blocked dopamine D1 receptors reversed these symptoms

– and therefore this is evidence proving the link between increased dopamine levels and schizophrenic symptoms and

• therefore this study supports the dopamine hypothesis of schizophrenia

BUT

• tenn et al 2003

• uses rats to find this which do not have the same brain structure, only similar too hoomans

• this means that both the amphithetamine and the dopamine antagonist may not have 100% had the same effect on rats and it would have done humans

and there may be other factors and effects that could have made this occur in rats

and therefore it means that it may not occur in humans

therefore the results of this study that increased dopamine levels cause schizophrenia and that they can be reversed by dopamine antagonists may not be applicable to humans w/ schizophrenia

due to genetic and biological differences between rats and human brains and the reactions to amphetamine and dopamine antagonists

The full meaning the study has low internal validity as it is inaccurate for humans as its made for rats

Question 16

Dopamine Hypothesis SZ

Alpert and Friedhoff (1980) - (Antagonist dont work)

and high eco + mundane

Answer 16

Alpert and Friedhoff (1980)

• Finds some patients found no improvment in SZ symptoms after Taking Dopamine Antagonists (to black dopamine receptors reducing Dope Lvls)

• this shows Dopamine cannkt be the only factor in SZ
– As Blocked dope receptors didn’t reduce the symptoms of SZ (which they should have if Excess Dopamine causes it)
– Sugesting Excess dopamine isnt the cause of SZ opposing the Dopamine Hypothesis.

But this research by Alpert and Friedhoff (1980) has High Ecological Validity and Mundane realism
– used real Dope Antagonists on real SZ patients in a real medical Setting (so task representive of real life (Mundane realism) and real Drugs (in tablet form) on real Patients so the results could and did occur in real life so it also has High ecological validity)

– therefore The experiment was highly representitive of real life treatments and the results are likley to reoccur in real life
– so Alpert and Friedhoff (1980) is Good evidence to oppose the dopamine hypothesis

Question 17

Dopamine Hypothesis SZ

Seeman (2013) +

Owen et al 1978 + (supports Seeman)

Number of receptors

Answer 17

Seeman 2013

• suggested a high N⁰ of active D2 dope receptors causes SZ
– as this means Dope is more likley to bind to a receptor carrying out its function

– this is thurther prooved by OWEN ET AL 1978

– who found an abnormaly large quantity of D2 receptors in SZ patients during a Post mortem Investigation
– gaining evidence for Seeman’s suggestion

this gives credit to the Neurobiological cause as it shows a greater N⁰ of D2 receptors are present on SZ patients linking them to it’s cause as more receptors means more binding so there is greater lvls of Dopamine in function
– Providing support for one of the Explenations of Hyperdopaminergia in the Dopamine Hypothesis, that claims an increased N⁰ of Dopmaine receptors in the post synapse may cause SZ

Question 18

Dopamine Hypothesis SZ

Aetiology Fallacy - (cant base theory om treatment effectivness)
limitaition/critisism

Answer 18

• The Idea that a dissorders cause can be determined by a treatments effectivness

– (in this case Dopamine Antagonists like Chlorlromazine decreasing lvls of Dopamine and Positive SZ symptoms, indicating excess lvls dopamine caused them)

– is a limitation, as this may not be the only cause of SZ, amd other factors of the drug may have caused this to occur

– The Invalidity of using Treatment Effectivness to determin the cause of a dissorder is called the Aetiology Fallacy

– as this may not be the only factor causing SZ, deeming the cause the inverse of the drugs main function as the soul cause is Reductionist and invalid.

– Therefore due to the Aetiology Fallacy, and the original dopmaine Hypothesis being based on the Dopamine Agonist Amphetamine creating Psychotic Symptoms when used to treat parkinsons
– It can be concluded that this basis of the Dopamine Hypothesis is Invalid as there may be other factors causings SZ, esspecialy as in both Dope Agonists and Antagonists they only increase or decrease the Positive Side Effects of SZ such as Hallucinations, and not the Negative ones such as poverty of speech

– This is therefore a limitation/critisism of the Dopmaine Hypothesis

Question 19

Dopamine Hypothesis SZ

The Effectivness of SGA opposes the Dopamine hypothesis

and howver more research

Answer 19

• Second generation Antipsychotics such as Clozapine or Risperidone reduce both Positive and Negative Symptoms of SZ
– this is as they bind D1 and D4 receptors together, Block D2 receptors AS WELL AS blocking Seritonin receptors AND NMDA Glutamate receptors

– This Critisises the Dopamine Hypothesis as first Generation Antipsychotics such as Haloperidol only blocked D2 receptors and Reduced Positive symptoms

– but these SGA also block Seritonin and Glutamate ones too, and reduce the Negative Symptoms of SZ

– This suggests Irregualr Seretoneric or Glutamageric Levels could Cause negative SZ symptoms

– Meaning Dopamine isnt the Soul cause of SZ, and there may be other NT that play a key role in it

– so the Dopamine Hypothesis may be Invalid as SZ may be caused by a more General Neurotransmiter Difference rather than Just Dopamine
and therefore this opposes the Original dopamine Hypothesis

HOWEVER

– both Seritonin and Glutamate have been found to have some interconnectivity in the levels or even Regulation of Dopamine, so their effect in SGA may be connected to Dopamine rather than their own individual effects for SZ

– thurthermore this needs more research as Dopamine as the cause of SZ from FGA has been researched for more than 70 years
– where as other NT from SGA have only been researched for around 30+ years,

– and therefore more research is needed for a clearer explenation of the effecrs of SGA and whether or not other NT play a role in The cause os SZ

– and therefore more research and evidence is needed for other NT to validly oppose the Dopamine Hypothesis

Question 20

Dopamine Hypothesis SZ

conclusion

Answer 20

It is likely that Excess Dopamine in the Messolimbic pathwat and a Lack of it in the Messocortical pathway both cause positive and Negative symptoms of SZ respectivley.

– an application of this knowlege is that these symptoms can be treated by drugs that Block these Dopamine receptors such as Clozapine, which as a SGA also blocks seritonin and NMDA Glutamate Receptors, reducing negative symptoms, possibky due to Glutamates Regulatory effects on dopamine, or that an lack of just dopamine may cause the increase of Seritonin, causing thurtger side effect, so reducing both negates this

– this shows how the Dopamine Hypothesis can be used Effectivly to Reduce the symptoms of SZ via Antipsychotic Drugs such as Clozapine

Question 21

Dopamine Hypothesis SZ

Depati and Lal (2001) -

Answer 21

Depati and Lal (2001)

– showed that apormorphine (dope agonist that stimulatss D2 receptors)
– doesn’t induce Psychotic Symptoms in non Psychotic clients, or increase them in diagnoses patients

– suggesting that Excess Dopamine (as Agonist acts as Dopamine) or Hypersensitive D2 receptors (as its stimulated) is not the cause of Psychotic Symptoms of SZ as the Dopamine Hypothesis suggests

–and therefore Depati and Lal (2001) opposes it

Question 22

Dopamine Hypothesis SZ

Falkai et al (1988) + post mortem high n d2, And Messolimbic

Answer 22

Falkai et al 1988

finds in a post mortem examination SZ patients have a higher N⁰ of D2 receptors than a non SZ control

So Abnormal D2 numbers in SZ links a Possible cause

also finds increases levels of dopamine in Brain structures and receptors e.g Left Amygdala

– Amygdala in messolimbic pathway
– excess dopamine in that pathway is theorised to result in possitive SZ symptoms

– thereflre the studdy supports, excess dopamine, abnormal n⁰ D2 receptors and the Hyperdopaminergia in the Messolimbic pathway
– all in the Dopamine Hypothesis so supports it

Question 23

Dopamine Hypothesis SZ

reductionist + diathesis stress moddle

Answer 23

– Explenation reductionist as it dosnt concider the Social explenation of SZ thats explored by the Social Causation Hypothesis

as The stresses of Busy urban life (urbanisity) or feeling part of an outgroup (minority or migrant status) or Your quality of life (social adversity) or social issolation can all possibly lead to the increase of the risk of SZ

therefore by not including this in the Dopamine Hypothesis its invalid and reductionist as other factors may also cause SZ

the Diathesis stress modle is a more valid explenation as it Conciders both Biological and Social in the explentaion of SZ, brain structure, NT and SCH are deemed as factors causing/ increasing the risk of SZ

and thus by concidering both nature and nurture factors, it is far less reductionist than the Dopamine Hypothesis and thus a better explenation

Question 24

Dopamine Hypothesis SZ

Lindstroem et al (1999)+ L-dopa + pet scan Int val

Answer 24

They Radioactivly labledna chemical L-Dopa (to see it in a PET scan (int val cuz objectivley measures what occurs, cant be wromg only misread)

– Administered to 10 SZ and 10 with no diagnosis

Ldopa taken up faster in SZ

Sugests more D2 Receptors in SZ Patients than ctrl

Supporting a cause of Hyperdopaminergia in the Dopamine Hypothesis