CAP5 Flashcards
Define affective instability
Emotional dysregulation as exaggerated reactions to negative or frustrating stimuli (unlike in impulsivity there is a rush of affect)
Emotional regulation involves what circuitry?
Orbital frontal cortex, amygdala, anterior cingulate, cerebellum (temporal)
What brain structures are involved in anxiety/hyperarousal?
Limbic system perceives stress resulting in the hypothalamus releasing CRF which stimulates the pituitary to release ACTH which stimulates the adrenals to release glucocorticoids. CRF = corticotropin releasing factor. ACTH = adrenocorticotrophic hormone
Acute stimulation of 5HT2a in the brainstem leads to what?
Myoclonus, disrupted slow wave sleep, and nocturnal awakenings
What is the data on tricyclic antidepressants in ADHD?
They are effective, albeit more for behavior than cognition perhaps
What percentage of those with Tourette’s disorder have ADHD?
For those 6 to 18 years old, 50 to 60% (Cohen and Leckman 1989)
What is noradrenergic deficiency syndrome?
Depression that is associated with fatigue, apathy, notable cognitive disturbance, impaired concentration, problems with sustaining and focusing attention, slow information processing, and decreased working memory
Acute stimulation of 5HT2a in the mesocortical pleasure center leads to what?
Decreased dopamine, which can lead to apathy or decreased libido
Acute stimulation of 5HT2a in the spinal cord leads to what?
Inhibition of the spinal reflexes of orgasm and ejaculation
Acute stimulation of 5HT2a in the basal ganglia leads to?
Akathisia, psychomotor retardation or agitation, parkinson’s, dystonia (because serotonin inhibits dopamine release)
Acute stimulation of 5HT2a and 2c in the projection from the raphe nuclei to the limbic cortex results in?
Acute mental agitation, anxiety, panic attacks
Projection of 5HT neurons from the raphe nuclei to which area leads to therapeutic action?
Frontal cortex
What does the presence of serotonin in the synaptic space lead to?
Postsynaptic receptors become desensitized (2a, 2c, 3). These receptors send information to the cell nucleus of the postsynaptic neuron resulting in the instruction to downregulate these receptors. The time course for this to happen corresponds to the tolerance of side effects.
The increased ratio of serotonin to serotonin receptors after antidepressant treatment as a mechanism of action is supported by what evidence among other?
Deceased suicidal and otherwise depressed patients have had more 5-HT2A receptors than normal patients. These considerations suggest that 5-HT2A overactivity is involved in the pathogenesis of depression.
What serotonin receptor does trazadone block?
5HT2a receptor. It also blocks reuptake but less so than other agents
By what process does trazodone effet sleep?
By inhibiting histamine H1 leading to sedation and by inhibiting 5HT2a which induces and restores slow wave sleep
When selective serotonin reuptake inhibitor treatment is initiated where does serotonin first rise?
Cell bodies in the raphe nuclei and not at the axon terminal where the re-uptake pump is located (somatodendritic autoreceptors 5HT1a)
Increased serotonin at the somatodendritic autoreceptor 5HT1a leads to?
Downregulation and densitization. Once desensitized and down regulated it can no longer efffectively inhibit its own release and the serotonin neuron is disinhibited. This correlates with time of onset of anti-depressant action
Mirtazapine blocks which alpha receptors?
Alpha 2
Mirtazapine inhibits which serotonin and histamine receptors?
2a, 2c, 3, H1
Mirtazapine’s blockade of which receptor contributes to its antidepressant effect?
5HT2a
Mirtazapine’s blockade of which receptors leads to anxiolysis and relaxation?
5HT2a, 5HT2c and H1
Mirtazapine’s blockade of which receptors mitigates side effects?
5HT2a, 5HT2c, 3
Mirtazapine’s blockade of which receptors leads to sedation?
5HT2a and H1