Schizophrenia + decision-making and impulsivity Flashcards
Describe the dopamine hypothesis for schizophrenia.
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
Provide examples of common cognitive deficits in patients with schizophrenia
- simple reaction time and processing speed
- attention
- verbal and visual learning and memory
- working memory
- executive functions
- social cognition
- intelligence
Name the major dopaminergic pathways.
4 anatomical dopaminergic pathways:
- nigrostriatal
- mesolimbic
- mesocortical
- tuberoinfundibular
Describe the principal mechanisms of action for L-DOPA used for treatment of parkinsonism.
- 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
Describe the principal mechanisms of action for antipsychotics.
Block the striatal dopamine D2-R to a higher or lesser degree, does not activate (antagonist) ==> positive symptoms slowly fades
Define the concept “cognitive control”.
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
Define the concept “decision-making”.
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
Provide examples of parameters that shape decision-making.
- available info (and attention to it)
- perceived raltive values (reward)
- past experiences
- emotions/states
- personality traits (e.g., impulsivity)
Describe major types of impulsivity.
Decisional
- delay discounting
- probabilistic discounting
- reflection impulsivity
Motor
- premature responding
- stopping inhibition
What tests can be used to asses cognitive control?
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
What tests can be used to asses impulsivity?
- 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
Define the concept “impulsivity”.
- 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
What are some impulse control disorders?
- ADHD
- antisocial personality disorder
- borderline personality disorder
What are the “positive” symptoms of schizophrenia?
Hallucinations, delusions,
disorganized speech (formal thought disorders) and
abnormal motor behavior
What are the “negative” symptoms of schizophrenia?
Diminished emotion
expression, avolition, anhedonia, alogia, asociality
Describe the most important side effects for antipsychotics.
“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
Describe the nigrostriatal dopaminergic pathway and the overall physiological function.
- 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
Describe the mesolimbic dopaminergic pathway and the overall physiological function.
- 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”)
Describe the mesocortical dopaminergic pathway and the overall physiological function.
- VTA –> prefrontal cortex
- Function: motivation, reward and desire, emotional response, learning and memory
- Major role: regulating executive functions/cognitive control
Describe the tuberoinfundibular dopaminergic pathway and the overall physiological function.
- Hypothalamus –> pituitary?
- Function: hormone secretion (prolactin)
Describe the principal mechanisms of action for dopamine agonists used for treatment of parkinsonism.
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
Describe the principal mechanisms of action for MAO inhibitors used for treatment of parkinsonism.
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
What are the general strategy when using MAO/COMT inhibitors, dopamine agonists, or L-DOPA for treatment of parkinsonism?
Purely symptomatic: increase dopamine or the effects of dopamine
Describe the principal mechanisms of action for COMT inhibitors used for treatment of parkinsonism.
- 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
