Dopamine Hypothesis for SZ (NT) (BIO) Flashcards
Dopamine Hypothesis SZ
Dopamine
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
Dopamine Hypothesis SZ
Glutamate
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
Dopamine Hypothesis SZ
GABA
Gaba is a neurotransmitter that’s purpose is to inhibit dopamine
Dopamine Hypothesis SZ
seritonin and dope
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
Dopamine Hypothesis SZ
neuron NT recap
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
Dopamine Hypothesis SZ
basic overview of the og dope hypothesis
The Dopamine hypothesis, a biochemical explanation of schizophrenia,
suggests that an excess of the neurotransmitter dopamine maybe responsible for schizophrenia
Dopamine Hypothesis SZ
how did it start
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
Dopamine Hypothesis SZ
lieberman et al 1987 +
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
Dopamine Hypothesis SZ
Hyperdopaminergia
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
Dopamine Hypothesis SZ
Hyperdopaminergia in the Mesolimbic pathway
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
Dopamine Hypothesis SZ
Hypodopamingeria in the mesocortical pathway
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
Dopamine Hypothesis SZ
Serotonin and negative symptoms
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
Dopamine Hypothesis SZ
Howes and Kapur 2009
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
Dopamine Hypothesis SZ
another origin story
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
Dopamine Hypothesis SZ
Tenn et al 2003 + and Animal research
• 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
Dopamine Hypothesis SZ
Alpert and Friedhoff (1980) - (Antagonist dont work)
and high eco + mundane
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
Dopamine Hypothesis SZ
Seeman (2013) +
Owen et al 1978 + (supports Seeman)
Number of receptors
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
Dopamine Hypothesis SZ
Aetiology Fallacy - (cant base theory om treatment effectivness)
limitaition/critisism
• 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
Dopamine Hypothesis SZ
The Effectivness of SGA opposes the Dopamine hypothesis
and howver more research
• 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
Dopamine Hypothesis SZ
conclusion
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
Dopamine Hypothesis SZ
Depati and Lal (2001) -
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
Dopamine Hypothesis SZ
Falkai et al (1988) + post mortem high n d2, And Messolimbic
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
Dopamine Hypothesis SZ
reductionist + diathesis stress moddle
– 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
Dopamine Hypothesis SZ
Lindstroem et al (1999)+ L-dopa + pet scan Int val
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
