Schizophrenia Flashcards
What is the peak age of onset of schizophrenia?
15-20 y/o
What general type of risk factors are associated with schizophrenia?
genetic and enviromental
How does the ventricle size in brain differ in individual with and without Schizophrenia?
An individual with Schizophrenia has a LARGER ventricular than someone without the condition
What is the function of COMT enzyme?
COMT stands for Catechole-O-methyltransferase
An enzyme the breaksdown catecholamines
Name 3 catecholamines
- dopamine ( DA)
- norepinephrine ( NE)
- Serotonin
3 categories of symptoms seen in Schizophrenia
- positive ( added)
- negative ( removed)
- Cognitive impairments
What are positive ( added) symptoms of Shizophrenia
- Hallucinations
- Delusions
- Disordered thoughts/speech
Which part of brain is negatively affected in auditory hallucinations in Schizophrenia?
Temporal lobe, primary and secondary auditory cortex
What is the drug haloperidol?
typical antipsychotic drug
A full agonist of dopamine
What is aripiproazole?
An atypical antipsychotic drug
A partial agonist of dopamine
maintains a lowered level of dopamine signaling
decreases the affect of lack of pleasure ( anhedonia)
What is chlorpromazine?
An typical antipsychotic drug that has a weaker affinity for D2 dopamine receptor. IT is an antagonist of D@ dopamine receptor
Which symptoms class is treated and worsened in schizophrenia?
The positive symptoms are treated ( results from too much levels of dopamine)
Th negative and cognitive deficit symptoms are worsened ( results in too little levels of dopamine)
catatonia
abnormal movement and behavior
Delusions
positive symptom of schizophrenia
normal perception that are explained by unrealistic interpretations
4 common themes of delusions
- perscutory- being harmed by a person/organization
- Referential-thing(s) in enviorment are directed to person ( gestures, objects)
- Grandiose-expectional power, abilitiies
- Religious
Bizarre delusion vs. non-bizarre delusion
bizarre delusion-defies nature, physics laws etc; not plausible
non-bizarre delusion-opposite of bizarre; could occur in nature
hallucinations
positive symptom in schizoprhenia
hearing of voices ( single or mulitple; positive or negative; from a familiar or unfamiliar person)
hallucination usu. auditory
perceived as real and cant be controlled
disordered thinking
positive symptom of shizophrenia
thought disorder inferred from speech
speech is disordered
4 Negative symptoms of schizophrenia
- flat affect-lack of emotion
- anhedonia-lack of pleasure/reward
- alogia-inability to speak
- avolition-lack of movement
3 cognitive symptoms of schizophrenia
- decreased executive function-hypofronatality
- poor attention
- decreased working memory
Hypofrontality
decreased function in frontal cortex
Test/task that measure executive function or hypofrontality
- Stroop test
2. Wisconsin card sorting
Task that measures working memory
N-bak test
Dopamine Theory of Schizophrenia
Increased dopamine causes psychotic behaviors seen schizophrenia
Name 4 tenets of Dopamine ( DA) Theory
- There is global and regional ( brain) excess DA levels
- Excess DA is due to increased turnover of DA and increased post-synaptic receptor function
- global excess DA in blood/in general
- Regional ( brain) excess DA in mesocortical and mesolimbic systems
Dopamine turnover
increased dopamine, means increased turnover or dopaminic metabolites
What is the signifcance of chlopromazine/thorazine?
antipsychotic drug first used in 1950s that changed how schizophrenia was medical treated
signifgantly decreased the mortality ( suicide) and morbidity ( symptoms) of schizophrenia
increased post-synaptic function
increased dopamine mean more release of dopamine to post synaptic neuron and thus increased activity/function
Describe dysregulation of dopamine (DA) in brain and what it means for treatment
- In mesocortical pathway, there is too little DA which is associated negative symptoms and cognitive defcits; treatment would decrease increase levels in brain
- In mesolimbic pathway, there is too much DA which is associated positive symptoms; treatment would decrease DA levels in brain
4 pathways that are mediated by dopamine in the brain
- mesocortical (negative symptoms and cognitive deficits)
- mesolimbic ( positive symptoms)
- Tuberinfundibular ( prolactin)
- Nigrostriatal ( movement, )
State Dopamine (DA) synaptic activity and schizophrenia symptoms
- Negative symptoms associated with too little DA in synapse
- Positive symptoms are associated with too much DA in synapse
Steps in synaptic physiology of dopamine receptor
1.Dopamine neuron on right that has an D2 autoreceptor ( receptor expressed by neuron releasing chemical )on it.
2. AP potential in dopamine neuron leads to release of dopamine neurotransmitter
3. dopamine binds to post synaptic neuron and causes downstream signaling
4 . Dopamine can also bind to the autoreceptor and suppress add’l release of dopamine ( negative feedback)
Steps in synaptic physiology of dopamine receptor
1.Dopamine neuron on right that has an D2 autoreceptor ( receptor expressed by neuron releasing chemical )on it.
2. AP potential in dopamine neuron leads to release of dopamine neurotransmitter
3. dopamine binds to post synaptic neuron and causes downstream signaling
4 . Dopamine can also bind to the autoreceptor and suppress add’l release of dopamine ( negative feedback)
Effect of antipsychotic on dopamine turnover
Chlorpromazine and haloperidol increase dopamine turnover
Effect of antipsychotic on dopamine turnover
Chlorpromazine and haloperidol increase dopamine turnover ( increased metabolites, breakdown products)
Effect of antipsychotic on dopamine neuron firing
Decrease firing of dopamine neuron
Effect of anti-psychotic on dopamine-mediated behavior
Decrease in dopamine results in slowed movement or bradykinesia or parkinsonism ( a side effect)
Common monoamine catecholeamines
- norepinephrine
- Dopamine
- Epinephrine
These are part of the same biosynthetic pathways; have related structures
Describe mechanism of action ( pharmadynamics) of typical antipsychotic drug on D2 receptors
- Drug acts as antagonist and blocks auto-receptor neuron and post-synaptic receptor which inhibits negative feedback,
- blockage causes increased autoreceptor neuron firing and dopamine release but this increased activity is ignored since the drug is blocking dopamine receptors on both neurons.
- Due to both receptors being blocked , there is decreased downstream signaling by post synaptic neuron
- Since dopamine is not being used and is just “hang out” in synaptic cleft, it will be degraded.
- Ultimate result of this drug is decreased dopamine levels ; main effect of drug is to block receptors
Dissociation constant (DC) of Antipsychotic drug
Affinity or how tightly bound a drug binds to dopamine D2 receptor
higher DC means lower affinity; drug has less affinity to receptor than dopamine itself
lower DC means more affinity: drug has more affinity to receptor than dopamine itself
What is the clincal dose-D2 receptor affinity relationship of antipsychotic drugs?
the higher the clinical dose, the less tightly the drugs binds to D2 receptor
Potency vs efficacy
Potency is an expression of the activity of a drug in terms of the concentration or amount of the drug required to produce a defined effect ( ie dose/dosing)
clinical efficacy judges the therapeutic effectiveness of the drug in humans ( what effect is being produced)
Potency doesnt necessarily equates to efficacy
Typical vs atypical drug
typical drugs correlate well with affinity to D2 receptor to have a good clinical efficacy
atypical drugs don’t correlate well with affinity to D2 receptors and have bad clinical efficacy
Side effects of typical drugs
typical drugs have a higher affinity for D2 receptor than dopamine itself and thus create side effects like parkinsonism and hyperprolactinemia
Anhedonia as side effect of antipsychotic drugs
drugs cause even more lack of pleasure/reduced motivation/sex drive which is symptom of schizophrenia itself
aripiprazole is used to treat this side affect
antipsychotics and dementia
dementia is contraindication for antipsychotics!
Late Developing side effects of antipsychotics
- Neuroleptic malignant syndrome ( life threatening, may require drug to be no longer used by person)
- Metabolic Syndrome ( with gain, HTN, diabetes, etc.)
- Tardive Dyskinesias ( opposite of parkinsonism, increased abnormal movement)
Pharmacological straightjacket
antipsychotic drugs that cause parkinsonism or dyskinesia, or decreased movement in people with schizophrenia
