PSU2003 W1 Schizophrenia 1 - (L) Flashcards
What are the general symptoms of Schizophrenia ?
Auditory/visual hallucination (prolonged periods), cogntiive problems, negative effects, mania, disorganised speech, delusions, paranoid, grandiose, persecution, inappropriate affect odd behaviour.
What are some of the historical perspectives on the causes of Schizophrenia ?
R.D. Laing (linked familial dynamics as the reason for schizophrenia but had no control condition) Freud (paranoid delusion sresult from repressed sexual urges which are striving for expression)
What are the limitation of these historical perspectives?
They lack evidence, R.D. Laing had no control condition and Freud did not use evidence
Explain the possible influence of genetics to the development of schizophrenia?
The concordance rate for schizophrenia is higher in monozygotic twins (45ù) compared to dizygotic (10%) this could show a genetic predisposition to schizophrenia.
Explain is the possible influence of the Environement to the development of schizophrenia?
The concordance rates are to low to be the sole factor, exposure to stressors is common ebfore an episode and the severity of the episode can be predicted by the amount of stress.
What are the main pharmacological treatments of schizophrenia?
Chlorpromazine and Reserpine, both discovered through luck
What is the dopamine theory of schizophrenia?
The thoery believes schizophrenic people have more D2 receptors which leads to more dopamine within the synaptic cleft, which leads to the positive symptoms (mania)
What is the etymology of Schizophrenia?
“A splitting of the mind”, skhizein “to split” and phren “heart, mind” Originally thought to be a breakdown of integration between emotion, thought and action.
What were R.D. Laing’s thoughts on schizophrenia?
Linked familial dynamics as the reason for schizophrenia but he had no control condition. [he did not believe schizophrenia was an illness he viewed it more as a way people cope with chaotic environments.]
Was R.D Laing correct (even thought he didn’t have a control condition)?
He was partially correct as environment does play a factor however it is not the sole cause.
What was Freud’s belief?
believed that “paranoid delusions result from repressed sexual urges which are striving for expression.” – no evidence
What are the concordance rates for Dizygotic and Monozygotic twins for schizophrenia?
45% and 10%
How were anti-psychotic drugs discovered?
Luck
How was Chlorpromazine discovered?
originally marketed as an antihistamine (used to treat fevers/allergies as an anti-inflammatory). French surgeon noticed it calmed normal patients when used as anti-inflammatory. Decided it might calm schizophrenics and it did
How was Reserpine discovered?
Taken from snale root plant to treat mental illness in india, also effective in treating schizophrenia.
What are the similarities between Chlorpromazine and Reserpine?
Both take 2-3 week sto work, symptoms like those in parkinsons start to emerge (loss of dopamine)
What role / How do these drugs work?
The drugs blcok dopamine which affects the substantia nigra (bring dopamine to emotion snad motor areas)
What is Chlorpromazine’s mode of action?
It blocks DA receptors and stops DA working, as they cannot bind to the receptors, this is done by a false transmitter (antagonsit)
What is Reserpine’s mode of action?
It deplete vesicles (pops them), reducing the amount fo DA that is released.
What is the dopamine hypothesis?
Drugs that reduce dopamine neurotransimmision reduce psychotic symptoms. Drugs that increase DA neurotransmission, produce psychotic symotoms, this led to the dopamien theory of schizophrenia.
What other drugs provide evidence for the dopamine hypothesis?
Cocaine psychosis, amphetamine psychosis (drugs that increase dopamine), They blcok the reuptake of dopamine which leaves more in the synaptic cleft, which causes schizophrenic like symptoms
What is Haloperidol?
Is an effective anti-psychotic but isn’t very good at binding to dopamine receptors, becuase there is more than 1 type of DA receptor
What is the role of dopamine receptors in the use of anti-psychotic drugs?
the efficacity of the drugs as a treatment for the symptoms can be prodicted by the efficacity of the drugs in binding to dopamine receptoss.
What are the types of DA receptors?
D1-LIKE (D1;D5) positively coupled to adenlyate cyclase, D2-LIKE (D2;D3;D5) negatively coupled to adenlyate cyclase.
What is a Adenylate cyclase?
Enzyme that helps send messages inside the cells.
What is pharmacological fallacy?
drug treating something, and it works in a certain way doesn’t mean that you had a problem of a reduction of that thing in the first place. But believing that is pharmacological fallacy.
How do PETs work?
Positron emission tomography make something radioactive, injecting it into the blood. It crosses the blood brain barrier into the brain, you then can use a scintillation counter to see where in the brain the radioactivity is and how much there is.
What did Seeman et al. 2000 show?
There is some evidence to suggest that there is an overactive dopamine system in some people with a diagnosis of schizophrenia.
What is the difference between schizophrenic people and the control?
Difference in receptors, greater number of dopamine reeptors in schizophrenic people.
What was a good predictor for how well the antipsychotic medication was going to work?
The number of dopamine receptors, the more receptors the better the treatment would be.
How is stress related to schizophrenia?
exposure to stressors is common before an episode and there is a correlation between the amount of stress and severity of episode
What is an exemple of a specific enironmental stressor linked to schizophrenia?
Bullying expereinces and psychotic expereinces (delusion) in non-schizophrenics
What are grandiose delusions (GDs)
delusions of grandeur are a subtype of delusion characterized by extraordinary belief that one is famous, wealthy, superior
What did Post-Mortem studies show?
More D2 receptors in the striata for pateints with schizophrenia (majoritivly were on anti-psychotics)
What did Abi-Dargham et al reveal?
An increase in D1 D2 receptors because tere is no possible why to show a greater increase without having a higher number of D2 receptors
What is the dopamine dysregulation hypothesis good for?
Good explanatin for the psychotic episodes
What is the dopamine dysregulation hypothesis not good for?
Cogntiive abnormalities remain unclear.
What was a good predictor of what?
Larger increase in D2 receptor availability in schizophrenic patients predicted a better treatment response for positive smptoms to the antipsychotic drugs (which elevated synaptic dopamine)
What was used to measure the dopamine depletion
SPECT and IBZM (D2 receptor antagonist)
How was dopamine deplition achieved?
Administrating tyrosine hydroxylase inhibitor a-MPT for 2 days
What did the dopamine deplition enable?
Enabled an indirect measure of the propotion of D2 receptors occupied by dopamine in baseline state.
What was a-MPT’s effect on symptoms?
exposure induced a significant reduction in severity of positive symptoms.
What are examples of Positive symptoms?
Represent an excess of typical function: Delusions, hallucinatino, inappropriate affect, disorganised speech or thought, odd behaviour.
What are examples of Negative symptoms?
Reductin or loss of typical function: affective flattening, avolition and catatonia.
What did adoption studies show?
The risk of schizophrenia is higher if the biological parents has the disorder compared to adoptive.
What could be some causes ?
Genetic susceptibility, early experiences.
What is the difference between atypical and typical anti-psychotics?
Typical anti-psychotics are the first generation whislt atypical are second generation and often the drug of choice but do not bind strongly to D2 receptors.
What could be a reason/casue for schizophrenia?
Dysregulation of dopaminergic transmission. Increase uptake increase activity of dopa decarboxylase (enzyme involved in dopamine synthesis)
What predicts a good response of positive symtoms a-MPT
High synaptic dopamine levels
What does high synaptic dopamine levels induce ?
a nonsignificant increase in negative symptomes
What is related to higher levels of free dopamine in the vicinity of D2 receptors or/and higher affinity of D2
a larger occupancy of strital D2 receptors by dopamine in patients vs control
What predicts a better/Faster response to atypical antipscyhotic drugs
High levels of synaptic dopamine at baseline
Schizophrenia Frequency
1% of the population
Original Definition of Schizophrenia
Breakdown of integration between emotion, thought and action.
What causes schizophrenia?
Brain: difference in functional connectivity, differences in neurotransmitters.
Historical Perspectives - R.D. Laing
Thought ‘normal’ was a product of repression denial, splitting, projection, introjection and other forms of destructive action on expeirence.
He believed schizophrenia was a way of coping with a disfunctional environement (family) and was normal.
Behavioural Genetics - Monozygotic/Dizygotic
Monozygotic - identical twins 100%
Dizygotic fratenal twins 50% (same as other simblings)
Schizophrenia Genetics - Monozygotic
45% concordance rate for schizophrenia.
Schizophrenia Genetics - Dizygotic
10% concordance rate for schizophrenia.
What is the main environmental factor?
Stress: exposure to stressors is common before an episode and there is a correlation between the amount of stress and severity of episode.
Spefcific envrionmental stressors - Schizophrenia
Richard Bentall researched on individual envrionemtnal factors (bullying- linked to delusions)
Specific environmental factor and how they might relate to specific symptoms in schizophrenia.
CAPE Scores
Mesure of psychotic experiences
Pharmacological Treatments - Reserpine
Taken from snake root plant. Used to treat mental illness in India. Also effective in treating schizophrenia
Mode of Action - Reserpine
Reserpine depletes vesicles (pops them) so reduce amount of DA that can be released, which depletes the brain of DA.
Dopamine - Schizophrenia Treatment
Drugs (Chlorpromazine and Reserpine) Block dopamine (DA) which affects the substantia nigra (brings dopamine to emotions and motor areas [Dorsal striatum]) and ventral tegmental area which creates Parkinson like symptoms
Mode of action - Chlorpromazine
Chlorpromazine blocsk DA receptors so stops the DA from binding the receptors.
False transmitter (antagonists) binds to DA receptors but has no effect, adn stops DA working as it can’t bind to the receptors.
The Dopamine Hypothesis - what lead to it?
Pharmacological treatment (Chlorpromazine and Reserpine) affect on dopamine pathways lead to the dopamine hypothesis.
Other evidence for DA hypothesis
Recreational drugs that can increase dopamine.
They act directly on dopamine, because they block reuptake (therefore leave more in the synapse cleft)
If you take high or prologued doses of these drugs you might get cocaine or amphetamine psychosis which has similar symptoms as schizophrenia.
Summary of DA theory
Drugs that reduce dopamine neurotransmission reduce psychotic symptoms.
Drugs that increase dopamine neurotransmission can produce psychotic symptoms.
This led to dopamine theory of schizophrenia
Efficacy of an anti-psychotic drug - receptors
Antischizophrenic efficacy is linked to how well they bind to dopamine receptors.
Possitive correlation between the abilitiy of typical neuroleptics (anti-psychotics) to bind to D2 receptors and their clinical potency.
Haloperidol - anti-psychotic
Haloperidol isn’t good at binding to dopamine receptors becuase there’s more than 1 type of DA receptors
Dopamine Receptors
D1 [D1 + D5]
D2 [D2 + D3 + D4]
What are Dopamine Receptors
Metabotropic receptors
When you bind to the receptor you produce change in the cell via a G protein stimulating second messenger systems, different enzyme and they can interfere with ion channels eventually and change the excitability of the neuron rather than being a simple channel.
D1-Like Dopamine Receptors
NOM?
D2 - like Dopamine receptors
NOM?
Adenylate cyclase
is an enzyme that helps send messages inside the cells
Newer drugs ‘atypical antipsychotics’ - DA receptors
(clozapine) bind specifficaly to different D2 like receptors, specifically D4
Seeman, Philip and Kapur, Shij 2000
Deplete the natural dopamine with a Reserpine type drug (pops vesicle) and see how many radioactive chemical (IBZM), which measure dopamin ereceptors.
1st looked the number of receptors inpresecen of dopamine then used reserpine adn sa an increase in receptors in peoplewith schizophrenia.
Treatment efficacy and dopamine receptors
The greater number of dopamine receptors they had in the first place indicates a good predictor of how much better they were goin gto get once on antipsychotic medication
Dopamine systems and Schizophrenics
Evidence that dopamine system is overactive in schizophrenics
R.D Laing Limitation
Heavy focus on family dynamics with no control condition
Lack of empirical evidence
Lack of focus on biological factors
