Anxiety - neurobiol and treatment Flashcards
AMYGDALA AND FEAR
i) which three things does the emotional response involve? what integrates these?
ii) which brain areas initiate HPA and symp NS activation? what does this lead to?
iii) which area initiates avoidance behaviour?
iv) what can lesions in the amygdala cause?
i) emotional response involves behaviour, autonomic responses and hormones
ii) midbrain, hypothalamis, pons and medulla initate the HPA/symp NS activation and this lead to increased vigillance
iii) the periacqueductal grey matter is involved in avoidance behaviour
iv) lesions in the amygdala can remove fear
AMYGDALA AND LEARNING OF FEAR
i) what two things does learning of fears depend on?
ii) name three stimuli that are automatically wired into the amydala to produce a fear response
iii) what does activation of
a) paraventricular nucleus
b) VTA and LC
c) lateral hypothalamus
cause release of and what does this consequently cause?
i) learning of fear depends on how the amygdala processes info and how it connects to other structures
ii) heights, loud noises and large animals
iii) a) PVN > ACTH release > corticosteroid release (stress reponse)
b) VTA/LC > DA, Ach, NA release > increased vigilance
c) lateral hypothalamus > symp activation > fight or flight response
FEARFUL STIMULI AND THE ACUTE STRESS RESPONSE
i) what is excited when sensory information passes to the amygdala? what does this lead to?
ii) which hormones does each component of the HPA axis release?
iii) what does the locus coruleus release?
iv) what does the LC and HPA axis trigger?
i) excitation of the LC and hypothalamus and this leads to the acute stress response
ii) Hypothalamus releases CRH
Pituitary gland release ACTH
Adrenal gland releases cortisol
iii) LC releases noradrenaline
iv) LC and HPA axis trigger the fight or flight response
REGULATION OF THE HPA AXIS
i) are A and B positive or negative regulation?
ii) explain the HPA axis (what is released, how does the hypothalamus respond? why? what signals are therefore sent?)
i) A = positive
(amygdala increases activation of the HPA)
B = negative
(hippocampus gives negative feedback to the HPA axis)
ii) cortisol is released into the blood from the adrenal gland and this is sensed by the hippocampus as it has lot of glucocorticoid receptors
- hippocampus sends negative feedback signals to downregulate the HPA axis when there are high levels of cortisol in the blood
CHRONIC STRESS
i) which receptors are activated in the hippocampus? and what does this cause in relation to calcium?
ii) what is the evidence that some anxiety disorders may result from diminished activity in the hippocampus?
iii) in animal studies - what is the effect on the brains of animals under chronic stress
iv) what is seen down the microscope when looking at brains that have been damaged by stress?
i) glucocorticoid receptor activation in the hippocampus which causes damage as there is increased calcium entry to neurons which causes excitotoxic cell death then the HC cant feedback to limit cortisol production
ii) in PTSD patients hippocampal volume is reduced
iii) animals under chronic stress can have smaller hippocampi
iv) when looking at brains damaged by stress there are decreased pyramidal cells in the hippocampus
SEROTONERGIC AND NORADRENERGIC SYSTEMS
i) which two brain areas respond when these systems are out of balance?
ii) what does each system regulate?
iii) what area of the brain does each system orignate from and name two areas they project to?
iv) what effect does 5HT have on LC firing?
v) what does dysregulation of these systems result in?
vi) how may the pathways involved be determined?
i) amygdala and hippocampus
ii) 5HT regulates mood and emotion
NA regulates arousal and attention (fight/flight)
iii) both originate from the midbrain and project through the forebrain to cortical and limbic areas
iv) 5HT will inhibit LC firing
v) dysregulation of the systems may result in fear or anxiety responses
vi) pathways involved can be determined by which drugs have anxiolytic effects (positive effects on reducing anxiety)
ANXIETY DISORDERS
explain how each is characterised
i) PTSD
ii) Panic disorder
iii) Generalised anxiety disorder
iv) Phobia
v) OCD
i) PTSD - persistent psychological stress following exposure to extreme stress eg war
ii) Panic - rapid onset attack of extreme fear and severe stress
iii) GAD - stress and anxiety in the absence of obvious precipitating stimulis
iv) Phobia - similar to GAD but triggered by specific objects or situations
v) OCD - frequently recurring/uncontrolled anxiety producing thoughts and impulses
PANIC DISORDER
i) how is it characterised?
ii) is it more likely to be acute or chronic?
iii) give five universal basic symptoms
iv) when is the most common time of onset? is it more common in men or women?
v) name three things it may often be accompanied by?
vi) a shift in the direction of which NT is seen in panic disorder? how may this be rectified?
i) charac by unrealistic and unfounded fear and anxiety
ii) more likely to be acute but can last for variable amounts of time
iii) universal basic symptoms - short of breath, irregular heartbeat, clammy, dizzy, faint
iv) most common time of onset is young adulthood
more common in women
v) may often be accompanied by depression, alcoholism or drug abuse
vi) a shift in the noradrenaline direction is seen - can be rectified by SSRIs to increase 5HT and push the balance back
TREATMENT OF PANIC DISORDER
i) which drugs are predominantly used? which receptor do they work at? what effects does this have?
ii) how do we know these drugs work?
iii) what is therefore one theory about the manifestation of anxiety in relation to reecptors?
iv) name one other drug and one non drug therapy that can also be used?
i) Benzodiazepenes - partial agonist at GABAa receptors
Effects = sedation, sleep, reduced muscle tone, anterograde amnesia
ii) know benzos work as giving a benzo antagonist such as flumazenil will produce a panic attack in patients with panic disorders but not in controls
iii) theory is that anxiety may result from fewer benzo receptors or by neuromodulation that blocks benzo binding on GABAa
iv) can also use an SSRI or CBT
TREATMENT OF ANXIETY DISORDERS
i) which two disorders do benzodiazapenes work well in and which two do they work not so well in?
ii) which drugs work well in OCD, PTSD, PD and GAD? what is a downside of using these?
iii) what receptor does buspirone work on? which disorder does it work for? how long does it take to exert therapeutic potential?
i) benzos work well for BAD and panic disorder but not so well for OCD and PTSD
ii) SSRIs work well for OCD, PTSD, PD and GAD but a downside is that they may initially be anxiogenic and may take a few weeks to work
iii) buspirone works on the 5HT1a receptor as a partial agonist - works for GAD but takes 406 weeks to exert therapeutic potential
DRUGS INCREASING GABA ACTIVITY
i) what can increasing GABA activity improve?
ii) name a GABA receptor partial agonist
iii) name two indirect agonists. how do these work?
iv) describe how it can be demonstrated that benzos are indirect agonists of GABA receptor?
v) what is the mechnaism of action of the GABA receptor in relation to ion movement?
i) increasing GABA activity can improve anxiety
ii) GABA partial agonist = alcohol
iii) indirect agonists = benzos and barbiturates
work by binding different sites to GABA on the receptor so they dont compete with GABA
iv) adding GABA + benzo + benzo antag has no effect on GABA but the benzo is cancelled out (therefore the benzo must have a different binding site to GABA)
v) GABA activating its receptor causes an influx of chloride ions and therefore hyperpolarisation
GABA-ERGIC DYSFUNCTION IN ANX DISORDERS
i) what can be radiolabelled and viewed on PET scanning to indicate a benzo binding site?
ii) what is the difference in the number of benzo binding sites seen in panic disorder patients?
iii) what do panic disorder patients lack inhibitory control of? what may this lead to?
i) flumazenil (benzo antagonist) can be radiolablled to see benzo bind sites
ii) panic disorder patients have less benzo binding sites
iii) PD lack inhibitory control of cortical and limbic regions which normally supress inappropriate fear response therefore this can lead to panic attacks
SEROTONERGIC SYSTEM AND ANXIETY
I) what class of drug are fluoxetine and prozac? what part of the serotonergic system to they work on? what does this lead to?
ii) which two sites does buspirone act on? what does this cause?
iii) when is symptomatic change seen from these drugs?
i) they are SSRIs which work on the 5HT reuptake transporter - they make more 5HT available and allow it to have prolonged action
ii) Buspirone acts on
1) 5HT1a receptor as a partial agonist on the post synaptic neuron = enhances 5HT effects on post syn neuron
2) Also acts on somatodendritic receptors on the pre synaptic cell to release more serotonin
iii) symptomatic change can take a few weeks to be seen and these drugs may be anxiety promoting initially
name drugs A & B
A = Buspirone
B = SSRIs such as prozac and fluoxetine
ANXIETY & DEPRESSION
i) what % of depressed patients show symptoms of GAD?
ii) which drug can treat both of these conditions?
iii) what demonstrates that the therapeutic effect of the drug is not just simply boosting the synaptic levels of serotonin?
iv) what is the mechanism of change on admin of these drugs?
i) 85% of patients with depression have symptoms of GAD
ii) SSRIs can treat both
iii) therapeutic action can take a few weeks to be visible - if it was just a case of boosting synaptic levels of 5HT the effect would be seen instantly
iv) adaptive changes in the nervous system to chronically elevated levels of serotonin
NEUROPLASTICITY & ANTIDEPRESSANTS
what do A & B stand for?
A = CREB
B = BDNF
