stress and mood disorders

topic 7

what are some of the shared stress responses to different stressful events

hunger

cold

overheating

attacking someone

being attacked

what does stress stimulate

tue sympathetic nervous system

what does stress inhibit

the parasympathetic nervous system leading to increased heartrate constriction of blood vessels dry mouth

activation of the stress response - amygdala

telencephalon

• central nucleus of the amygdala - i nreposne to homeostatic challenges

• medial nucleus of the amygdala - in response to psychogenic challenges

• amygdala activates the sympathetic nervous system and the HPA axis

activation of the stress response - subgenual anterior cingulate cortex

sgACC - telencephalon

• indirect activation

• combination of this and amygdala active the stress response

activation of the stress response - activation of either brain area

activates the sympathetic nervous sytem

activates the HPA AXIX

they are normally both activated together

what happens in the regulation of the HPA axis

the body isnt efficient in the stress response and overtime the bosy will shut down

when the stress is over the hormone will decreases as they are naturally cleared from the body. you need the clearing to occur and you also need to stop producing more in order for the response to stop.

what type of feedback is the HPA axis

negative feedback loop

what occurs in the HPA negative feedback lopp

direct negative feedback of cortisol on the PVN via glucocorticoid receptors

cortisol stops the release of more ATCH

what does the hippocapus do in the HPA axis negative feedback

indirect inhibition - it has many receptors of cortisol and contains many MR and glucocorticoid receptors

intermediate-term feedback - returns psychogenic stress response back to baseline - its main job is to bring back down the levels

how does the HPA axis go

hypothalamus —> anterior pituitary —> adrenal cortex

then negative feeback

what are the symptoms of major unipolar depression

depressed mood

sleeping issues

fatigue

change in appetite

feelings of worthlessness

all have to be debilitating and no easily explaied by outside factors

what does depression do to the HPA axis

dysregulation of the HPA axis is common in affective disorders

• either constantly high levels of cortisol but not all with depression making it so complex

• with low they can also be increased change of depression

what is the chronic stress positive feedback

amygdala stimulates the HPA axis.

glucocorticoids activate the locus coeruleus (has noradrenergic projections which activates the amygdala)

short term stress response cuts short the system and begins to reduce - if it is chronic it will ocntinue to trigger its self and not need external - when it has been active for a long time it will reduce the negative feedback loop

what happens when chronic stress reduced the negative feedback

repeated stimulation by glucocorticoids reduces the sensitivity of receptors in the hippocampus - chronically high glucocorticoids also damage hippocampal neurons leading to further reduction of negative feedback.

what can chronic stress do to the negative feedback loop

it can damage the feedback making it easier and easier for stress to be activated for a longer time. leading to depression with some symptoms still not fully understood the individual differences

over stimulation can also cause the negative feedback not to work as well

how is the link between depression and stress strong

when drug work they reduce activity in the sub-genual anterior cingulate cortex (that activates the stress response) so the link is strong - successful treatments of depression also targets the stress response.

how does depression effect sleep

the time it takes to fall into sleep takes less time in those who have depression - they also quickly go into REM sleep (more and earlier) there is no time for the transitional stages to occur to little slow wave sleep too

how can REM deprivation help the depressed

for some it has lasting remission from depression when carried out for multiple nights

what are monamine effect of chronic stress

depletion of noradrenaline from the locus coeruleus

depletion of serotonin from raphe nucleus

depletion of dopamine from ventral tegmental areas to n accumbens and prefrontal cortex

what occurred when patients were given reserpine (a mono-amine antagonist)

normally given for increased blood pressure but 15% of those how took it go depression

suggests that the depletion of monoamines may lead to depression

how much 5-hyprocyindoleactic acid do depressed people have in cerebrospinal fluid

they tend to have less as they have less serotonin

(5-hyproxyindoleacetic acid is a breakdown produce of serotonin so makes sense that they would have less)

what happens in a tryptophan depletion experiment

get it from diets - if you gave someone an increase in all other mono-amines then the levels of it would decrease and it wont pass the blood brain barrier meaning you cant make serotonin

what would happen if you did the tryptophan depletion experiment on someone who recovered from depression with SSRIs

they would fall back into depression

what drug targets monoamines

SSRIs

when do SSRIs start to work

after a few weeks

how do the auto-receptors adapt to SSRIs

initally SSRIs increase 5HT levels in the synapse by blocking the reuptake channels.

the auto-receptors respond to this and reduce the 5HT released through negative feedback

this leads to no change in 5HT levels at the target cells

it takes around 2 weeks for the autoreceptors to adapt to higher levels of 5HT (build tolerance)

how could the brain recover from depression

anti-depressants increases neurogenesis

in rodents the time it takes for SSRIs to decrease depressive symptoms is the same amount of time it takes for the physiological processes to be brought back to normal

what would happen if you just came off SSRIs

would probably end up in a worse position as the body is too adjusted to them

what is the physiological action of ketamine

it is a NMDA-R antagonist

it also blocks the formation of new memories like alcohol

ketamine and depression

a sub-anaesthetic dose can have a profound effect within hours of injection - seems to work through new synapse formation in anterior cingulate cortex

ketamine and dopamine

NMDA-R antagonists can influence dopamine release in the n accumbens