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Georgetown Neurophysiology_Spring 2019 > Schizophrenia > Flashcards

Schizophrenia Flashcards

1
Q

What is the peak age of onset of schizophrenia?

A

15-20 y/o

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2
Q

What general type of risk factors are associated with schizophrenia?

A

genetic and enviromental

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3
Q

How does the ventricle size in brain differ in individual with and without Schizophrenia?

A

An individual with Schizophrenia has a LARGER ventricular than someone without the condition

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4
Q

What is the function of COMT enzyme?

A

COMT stands for Catechole-O-methyltransferase

An enzyme the breaksdown catecholamines

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5
Q

Name 3 catecholamines

A
  1. dopamine ( DA)
  2. norepinephrine ( NE)
  3. Serotonin
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6
Q

3 categories of symptoms seen in Schizophrenia

A
  1. positive ( added)
  2. negative ( removed)
  3. Cognitive impairments
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7
Q

What are positive ( added) symptoms of Shizophrenia

A
  1. Hallucinations
  2. Delusions
  3. Disordered thoughts/speech
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8
Q

Which part of brain is negatively affected in auditory hallucinations in Schizophrenia?

A

Temporal lobe, primary and secondary auditory cortex

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9
Q

What is the drug haloperidol?

A

typical antipsychotic drug

A full agonist of dopamine

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10
Q

What is aripiproazole?

A

An atypical antipsychotic drug

A partial agonist of dopamine

maintains a lowered level of dopamine signaling

decreases the affect of lack of pleasure ( anhedonia)

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11
Q

What is chlorpromazine?

A

An typical antipsychotic drug that has a weaker affinity for D2 dopamine receptor. IT is an antagonist of D@ dopamine receptor

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12
Q

Which symptoms class is treated and worsened in schizophrenia?

A

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)

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13
Q

catatonia

A

abnormal movement and behavior

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14
Q

Delusions

A

positive symptom of schizophrenia

normal perception that are explained by unrealistic interpretations

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15
Q

4 common themes of delusions

A
  1. perscutory- being harmed by a person/organization
  2. Referential-thing(s) in enviorment are directed to person ( gestures, objects)
  3. Grandiose-expectional power, abilitiies
  4. Religious
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16
Q

Bizarre delusion vs. non-bizarre delusion

A

bizarre delusion-defies nature, physics laws etc; not plausible

non-bizarre delusion-opposite of bizarre; could occur in nature

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17
Q

hallucinations

A

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

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18
Q

disordered thinking

A

positive symptom of shizophrenia

thought disorder inferred from speech

speech is disordered

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19
Q

4 Negative symptoms of schizophrenia

A
  1. flat affect-lack of emotion
  2. anhedonia-lack of pleasure/reward
  3. alogia-inability to speak
  4. avolition-lack of movement
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20
Q

3 cognitive symptoms of schizophrenia

A
  1. decreased executive function-hypofronatality
  2. poor attention
  3. decreased working memory
21
Q

Hypofrontality

A

decreased function in frontal cortex

22
Q

Test/task that measure executive function or hypofrontality

A
  1. Stroop test

2. Wisconsin card sorting

23
Q

Task that measures working memory

A

N-bak test

24
Q

Dopamine Theory of Schizophrenia

A

Increased dopamine causes psychotic behaviors seen schizophrenia

25
Q

Name 4 tenets of Dopamine ( DA) Theory

A
  1. There is global and regional ( brain) excess DA levels
  2. Excess DA is due to increased turnover of DA and increased post-synaptic receptor function
  3. global excess DA in blood/in general
  4. Regional ( brain) excess DA in mesocortical and mesolimbic systems
26
Q

Dopamine turnover

A

increased dopamine, means increased turnover or dopaminic metabolites

27
Q

What is the signifcance of chlopromazine/thorazine?

A

antipsychotic drug first used in 1950s that changed how schizophrenia was medical treated

signifgantly decreased the mortality ( suicide) and morbidity ( symptoms) of schizophrenia

28
Q

increased post-synaptic function

A

increased dopamine mean more release of dopamine to post synaptic neuron and thus increased activity/function

29
Q

Describe dysregulation of dopamine (DA) in brain and what it means for treatment

A
  1. In mesocortical pathway, there is too little DA which is associated negative symptoms and cognitive defcits; treatment would decrease increase levels in brain
  2. In mesolimbic pathway, there is too much DA which is associated positive symptoms; treatment would decrease DA levels in brain
30
Q

4 pathways that are mediated by dopamine in the brain

A
  1. mesocortical (negative symptoms and cognitive deficits)
  2. mesolimbic ( positive symptoms)
  3. Tuberinfundibular ( prolactin)
  4. Nigrostriatal ( movement, )
31
Q

State Dopamine (DA) synaptic activity and schizophrenia symptoms

A
  1. Negative symptoms associated with too little DA in synapse
  2. Positive symptoms are associated with too much DA in synapse
32
Q

Steps in synaptic physiology of dopamine receptor

A

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)

33
Q

Steps in synaptic physiology of dopamine receptor

A

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)

34
Q

Effect of antipsychotic on dopamine turnover

A

Chlorpromazine and haloperidol increase dopamine turnover

35
Q

Effect of antipsychotic on dopamine turnover

A

Chlorpromazine and haloperidol increase dopamine turnover ( increased metabolites, breakdown products)

36
Q

Effect of antipsychotic on dopamine neuron firing

A

Decrease firing of dopamine neuron

37
Q

Effect of anti-psychotic on dopamine-mediated behavior

A

Decrease in dopamine results in slowed movement or bradykinesia or parkinsonism ( a side effect)

38
Q

Common monoamine catecholeamines

A
  1. norepinephrine
  2. Dopamine
  3. Epinephrine

These are part of the same biosynthetic pathways; have related structures

39
Q

Describe mechanism of action ( pharmadynamics) of typical antipsychotic drug on D2 receptors

A
  1. Drug acts as antagonist and blocks auto-receptor neuron and post-synaptic receptor which inhibits negative feedback,
  2. 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.
  3. Due to both receptors being blocked , there is decreased downstream signaling by post synaptic neuron
  4. Since dopamine is not being used and is just “hang out” in synaptic cleft, it will be degraded.
  5. Ultimate result of this drug is decreased dopamine levels ; main effect of drug is to block receptors
40
Q

Dissociation constant (DC) of Antipsychotic drug

A

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

41
Q

What is the clincal dose-D2 receptor affinity relationship of antipsychotic drugs?

A

the higher the clinical dose, the less tightly the drugs binds to D2 receptor

42
Q

Potency vs efficacy

A

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

43
Q

Typical vs atypical drug

A

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

44
Q

Side effects of typical drugs

A

typical drugs have a higher affinity for D2 receptor than dopamine itself and thus create side effects like parkinsonism and hyperprolactinemia

45
Q

Anhedonia as side effect of antipsychotic drugs

A

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

46
Q

antipsychotics and dementia

A

dementia is contraindication for antipsychotics!

47
Q

Late Developing side effects of antipsychotics

A
  1. Neuroleptic malignant syndrome ( life threatening, may require drug to be no longer used by person)
  2. Metabolic Syndrome ( with gain, HTN, diabetes, etc.)
  3. Tardive Dyskinesias ( opposite of parkinsonism, increased abnormal movement)
48
Q

Pharmacological straightjacket

A

antipsychotic drugs that cause parkinsonism or dyskinesia, or decreased movement in people with schizophrenia

Georgetown Neurophysiology_Spring 2019 (25 decks)

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