ADHD Flashcards
What are the effects of noradrenergic receptors upon the ADHD profile.
α2 is responsible for focused attention. Drugs that act as agonists include guanfacine and clonidine.
α1 is responsible for arousal and viligance and thus involved in flexible attention and distractibility
β1 is also responsible for arousal and viligance, as well as emotional learning
Describe NE neurons firing patterns in the PFC according to one’s arousal state
- high tonic firing during stress
- moderate tonic firing with phasic responses to relevant stimuli during non-stressed waking
- low tonic firing during SWS and drowsiness
- silent during REM
What is the effect of low DA / NA in the frontal cortex?
- distractibility
- impulsivity
- impaired working memory
What is the effect of high DA / NA in the frontal cortex?
- distractibility
- stress
- hyperactivity
- impaired mental shifting
What is the underlying neurobiological mechanism of ADHD? Dicuss the role of DA and NE upon the information transmission.
An imbalance of dopamine and noradrenaline causes difficulty to judge the importance of a stimuli.
D1 receptors are excitatory, and allow for the increase of cAMP and with that, the opening of cAMP ligated potassium channels which causes the pyramidal neurons in the prefrontal cortex to leak current and thus inhibit AP for irrelevant information.
α2a receptors are inhibitory and cause the reduction of cAMP which in turn, allows for prevention of current leakage and thus enhance the AP for relevant information.
What is the role of dopamine in the prefrontal cortex?
To couple salience to incoming stimuli which means on one end to calculate error predictions to reward and on the other hand to decrease the sensitivity to irrelevant cues.
How does dopamine deficiency lead to inattention?El
Dopmine works upon inhibitory autoreceptors which keeps dopamine levels stable. When dopamine is insufficient, postsynaptic D1 receptors are not optimally saturated and there will not be enough autoregulation. Therefore, slight increase will skyrocket its effect and preventing from optimal physiological range.
How does ADHD medication work?
Elevate dopamine levels (which can also act upon noradrenaline) to saturate the D1 autoreceptors and keep DA levels more stable.
Improves emotion regulation by amygdala activation.
low limbic DA tone → anhedonia → delay aversion → low frustration threshold → anger bursts → regret / guilt / shame
Which brain areas are affected in ADHD?
dlPFC activity is lower in ADHD patients compared to HC, which impairs goal-orientated behaviour.
Dopamine deficiency in the mesolimbic system, which can cause anhedonia.
Increased
Do selective NET inhibitors also increase dopamine?
Yes - in the prefrontal cortex where there is high NET expression and low DAT expression.
No - in the nAcc and striatum because there’s practically no NET and NE present. So, no risk for addiction.
What are three stimulants that boost mesolimbic dopamine?
- Methylphenidate: a non-competative inhibitor
- dexamfetamine -> slow and gradual release
- amphetamines -> competitive inhibitor, which is also taken up by vesicle transporter
- Guanfacine -> activates α2a receptors to prevent distractibilty
What are shared neurobiological changes in depression, anxiety and ADHD?
- Reduced dlPFC functioning: impaired executive function
- ADHD: lacking top-down control results in impulsivity
- Depression: lack of cognitive flexibility, inability to disengage from negativity
- Anxiety: lack of shifting, inability to correct an inflated estimate of adverse events
- Deficient mesolimbic DA transmission: anhedonia
- ADHD: Lack of ability to attribute salience to reward-predicting cues
- Depression: lack of ability to attribute salience to pleasurable events
- Increased amygdala reactivity: emotional dysregulation
- ADHD: emotional lability, frustration and/or anxiety during delayed gradification
- Depression: ruminative thoughts, irritability, DMN hyperactivity
- Anxiety: panic, excessive worrying, DMN hyperactivity
What is the behaviour of dopamine during reward cues and anticipatory reward cues in depression and ADHD?
- Reward anticipation can be measured by dopamine spikes in the nucleus accumbens
- In ADHD patietns, dopamine levels are decreased in reward anticipation and increased in reward delivery → causing frustration and anxiety during reward delay
- In depressed patients, dopamine release is reduced in both reward anticipation and delivery, suggestion anhedonia
