PSY2003 W1 Schizophrenia 1 - R Flashcards
Dopamine hypothesis, Van Rossum in 1967
Seeman and Kapur (2000)
Drugs have different strengths at the receptor.
The strength (potency) depends on the dissociation constant at D2 (the break down) related to the realise rate of drugs from the D2 receptor (DA D2 Release clozapine and quetiapine more rapidly than other antipsychotic drugs).
Post-Mortem studies - dopamine hypothesis
Seeman and Kapur (2000)
Found more D2 receptors in the striata of patients with schizophrenia but they were majoritevely treated with antipsychotics (raising the risk of those drugs contirbuting in the increase of D2 receptors)
More D2 receptors in the striata for pateints with schizophrenia (majoritivly were on anti-psychotics)
Abi-Dargham et al
Seeman and Kapur (2000)
revealed an increase in DA D2 receptors because there is no possible why to show a greater increase without having higher number of D2 receptors.
Strenght of the dopamine dysregulaiton hypothesis as an explanation for Schizophrenia
Seeman and Kapur (2000)
psychotic episode
Increased baseline occupancy of D2 receptors by dopamine in Schizophrenia
Abi-Dargham et al., (2000)
increase of the use D2 receptors by DA in schizephenia.
Compared how available D2 receptors before and during pharmacologically induced acute dopamine depletion.
What results were a good predictor of what?
Abi-Dargham et al., (2000)
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)
Dopamine dysregulation - enzyme
Abi-Dargham et al., (2000)
Evidence shows a dysregulation of dopaminergic transmission in schizophrenia. Increase uptake in consistent with increased activity of dopa decarboxylase (= enzyme involved in dopamine synthesis)
What was used to measure the dopamine depletion
Abi-Dargham et al., (2000)
SPECT (single-photon computerized emmission tomography) and IBZM (D2 receptor antagonist)
What was used/How did they ‘delete’ dopamine?
Abi-Dargham et al., (2000)
Dopamine depletion was achieved by administrating tyrosine hydroxylase inhibitor a-MPT for 2 days. Indirect measure of the propotion of D2 receptors occupied by dopamine in baseline state (‘unmasking receptors’)
What happened after MPT exposure?
Abi-Dargham et al., (2000)
D2 receptors were significantly more available after a-MPT exposure compared to baseline, specifically in phrenic patients.
What was a-MPT’s effect on symptoms?
Abi-Dargham et al., (2000)
exposure induced a significant reduction in severity of positive symptoms.
What predicted good response of positive symptoms with exposure to a-MPT
Abi-Dargham et al., (2000)
High synaptic dopamine levels but it induced a nonsignificant increase in negative symptoms.
What did dysregulation of dopamine transmission predict?
Abi-Dargham et al., (2000)
of better response of positive symptoms to treatment.
What may be related to the larger occupancy of D2 receptors by dopamine in patients versus wontrol
Abi-Dargham et al., (2000)
may be related to higher levels of free dopamin ein the vicinity of D2 receptors hgiher affinity of D2 receptors for dopamine or some combination of both factors
Was there a correlation between severity of positive symptoms and occupancy of strital D2 receptors by dopamine
Abi-Dargham et al., (2000)
No correlation
Positive Symptoms
Pinel, J. Biopsychology
Represent an excess of typical function:
Delusions (being controlled, persecuted, of grandeur)
Hallucinations,
Inappropriate affect (failure to react with appropriate emotion to positive or negative events),
Disorganized speech or thought (illogical thinking, beliefs)
Odd behaviour (difficulty with everyday tasks, hygiene and talking rhymes).
Negative Symptoms
Pinel, J. Biopsychology
Represent a reduction or loss of typical function:
Affective flattening (diminished emotional expression),
Avolition (reduction of motivation),
Catatonia (motionless).
Adoption studies
Pinel, J. Biopsychology
risk of schizophrenia is higher if the biological parents had the disorder whilst there was no risk if the adoptive parents had the disorder.
Schizophrenia - Multiple causes
Pinel, J. Biopsychology
Genetic susceptibility
Early experience (birth complication, maternal stress, prenatal infections, Socioeconomic factors, urban birth childhood adversity)
Thought to alter typical neurodevelopment leading to schizophrenia if you are genetically susceptible.
Typical Anti-psychotics
Pinel, J. Biopsychology
first generation of anti-psychotic drugs.
Atypical anti-psychotics
Pinel, J. Biopsychology
second generation antipsychotic are often the drugs of choice for treatment. Effective against schizophrenia but yet do not bind strongly to D2 receptors. (e.g. clozapine has an affinity for D1 receptor, D4 receptors and several serotonin and histamine receptors.)
Schizophrenia and brain structure changes
Pinel, J. Biopsychology
1st generation of studies reported enlarged ventricle and fissures which reduced brain volume. A study also found that the hippocampus, amygdala, thalamus and nucleus accumbent were smaller in those with schizophrenia.
Limitation of the dopamine dysregulation hypothesis as an explanation for schizophrenia
psychological and cognitive abnormalities
What predicted a better response for positive symptoms to antipsychotic drugs ?
Larger increase in D2 receptor availability in schizophrenic patients predicted a better treatment response )
What is a-MPT
tyrosine hydroxylase inhibitor
What could be the cause for schizophrenia?
Dysregulation of dopaminergic transmission. Increase uptake increase activity of dopa decarboxylase (enzyme involved in dopamine synthesis)
What predicts a good response of positivve symptoms 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
