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NS2: module 5 > Schizophrenia + decision-making and impulsivity > Flashcards

Schizophrenia + decision-making and impulsivity Flashcards

1
Q

Describe the dopamine hypothesis for schizophrenia.

A

Hyperactivity in subcortical regions (striatum, mesolimbic pathway) leads to psychosis (mainly D2-Rs involved), while hypoactivity in frontal cortex leads to
negative symptoms and cognitive deficits

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1
Q

Provide examples of common cognitive deficits in patients with schizophrenia

A
  • simple reaction time and processing speed
  • attention
  • verbal and visual learning and memory
  • working memory
  • executive functions
  • social cognition
  • intelligence
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2
Q

Name the major dopaminergic pathways.

A

4 anatomical dopaminergic pathways:
- nigrostriatal
- mesolimbic
- mesocortical
- tuberoinfundibular

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3
Q

Describe the principal mechanisms of action for L-DOPA used for treatment of parkinsonism.

A
  • is an intermidiate of dopamine (tyrosine –> L-DOPA –> dopamine)
  • not degraded in the gut (dopamine is)
  • is given togerther with DCI, which inhibits conversion of L-DOPA –> dopamine
  • DCI cannot cross the BBB, only L-DOPA can (converted to dopamine in the brain)
  • might also treat symptoms caused by loss of NE
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4
Q

Describe the principal mechanisms of action for antipsychotics.

A

Block the striatal dopamine D2-R to a higher or lesser degree, does not activate (antagonist) ==> positive symptoms slowly fades

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5
Q

Define the concept “cognitive control”.

A

Executive function:
- how outside info (sensory input), internal states (emotions and mood), experience (learning and memory), personality traits, are integrated to shape our behavior (motor outputs).
- allows us to perform goal-oriented behaviors that will serve long-term survival

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6
Q

Define the concept “decision-making”.

A

simplest form:
- yes/no of perception of sensory input
more complex:
- from yes/no to 2 or more different alternatives (choices)
- based on repeated sampling of the available evidence (monitor for changes)
- include evaluation of value and preferences

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7
Q

Provide examples of parameters that shape decision-making.

A
  • available info (and attention to it)
  • perceived raltive values (reward)
  • past experiences
  • emotions/states
  • personality traits (e.g., impulsivity)
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8
Q

Describe major types of impulsivity.

A

Decisional
- delay discounting
- probabilistic discounting
- reflection impulsivity

Motor
- premature responding
- stopping inhibition

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9
Q

What tests can be used to asses cognitive control?

A

stroop test: interference from irrelevant info (wrong word to color)
Tower of London/Hanoi: planning
Wisconsin card sorting: set-shifting, adapting response to changing rules

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10
Q

What tests can be used to asses impulsivity?

A
  • delay discounting: reinforced by food treats (rodent), money (human) or marshmellows (young humans) - the longer you wait, the better the treat
  • gambling tasks: probalistic discounting
  • bead jar test: reflection impulsivity
  • 5-choise seriel reaction time task: continous performance test
  • go/no-go task: inhibiting an initiated action
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11
Q

Define the concept “impulsivity”.

A
  • dimensional construct of personality
  • a tendency to do things without planning or foresight
  • “failure” to resist an impulse, temptation, or drive to perform an act that is harmful to the person or others
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12
Q

What are some impulse control disorders?

A
  • ADHD
  • antisocial personality disorder
  • borderline personality disorder
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13
Q

What are the “positive” symptoms of schizophrenia?

A

Hallucinations, delusions,
disorganized speech (formal thought disorders) and
abnormal motor behavior

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14
Q

What are the “negative” symptoms of schizophrenia?

A

Diminished emotion
expression, avolition, anhedonia, alogia, asociality

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15
Q

Describe the most important side effects for antipsychotics.

A

“Old” antipsychotics
- parkinsonism: adverse effects in terms of “extrapyramidal symptoms” (movement disorder) due to blockade of the nigrostriatal dopaminergic pathway (becomes irreversible with time)

“Newer” antipsychotics:
- weight gain and T2D
- D2-R blockade and affinity for other receptors (e.g., 5HT2A antagonism) –> increased dopamine in the nigrostriatal pathway = prevent movement disorders

16
Q

Describe the nigrostriatal dopaminergic pathway and the overall physiological function.

A
  • Substantia nigra pars compacta –> BG (putamen and caudate)
  • act mainly on medium spiny neurons in the dorsal striatum expressing either preferentially D1-Rs (direct pathway) or D2-Rs (indirect)
  • Function: motor control - gating movement initiation and selection
17
Q

Describe the mesolimbic dopaminergic pathway and the overall physiological function.

A
  • VTA –> nucleus accumbens (ventral striatum) (also projections to e.g., the amygdlaa and hippocampus)
  • Function: motivation, reward and desire, emotional response, learning and memory
  • Major role: reward-related cognition (encode incentive salience or “wanting”)
18
Q

Describe the mesocortical dopaminergic pathway and the overall physiological function.

A
  • VTA –> prefrontal cortex
  • Function: motivation, reward and desire, emotional response, learning and memory
  • Major role: regulating executive functions/cognitive control
19
Q

Describe the tuberoinfundibular dopaminergic pathway and the overall physiological function.

A
  • Hypothalamus –> pituitary?
  • Function: hormone secretion (prolactin)
20
Q

Describe the principal mechanisms of action for dopamine agonists used for treatment of parkinsonism.

A

Synthetic dopamine agonists used to increase the effect of dopamine:
- e.g., ropinirol or pramipexol
- high affinity for D2-D4-Rs
- lower affinity for D1-D5-Rs
- 1st line treatment for patients < 70 years
- can be combined with MAO inhibitors and L-DOPA

21
Q

Describe the principal mechanisms of action for MAO inhibitors used for treatment of parkinsonism.

A

MAO = monoamine oxidase
- intracellular

Inhibitor:
- selegilin
- alternative 1st line treatment for patients < 70 years
- can be combined with dopamine agonist and L-DOPA
- inhibits degradation of dopamine

22
Q

What are the general strategy when using MAO/COMT inhibitors, dopamine agonists, or L-DOPA for treatment of parkinsonism?

A

Purely symptomatic: increase dopamine or the effects of dopamine

23
Q

Describe the principal mechanisms of action for COMT inhibitors used for treatment of parkinsonism.

A
  • COMT = catechol-O-methyltransferase
  • extrecellular

Inhibitors:
- entakapon
- together with L-DOPA –> reduce so-called “on-off” phenomenon
- prolongs the beneficial effect of L-DOPA
- inhibits degradation of dopamine

NS2: module 5 (2 decks)

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