Cortisol elicits how many successive phases of stress responses and what are they?
- response from limbic system which are projected to PVN of hypothalamus & HPA axis; cortisol level rises & peaks at 30-45 min
- stress phase: cortisol binds to MR to maintain HPA activity & control sensitivity to stress; enhanced arousal, vigilance, arousal, attention & alertness are non-genomic action through MRs
- recovery & adaptive phases (memory formation): 1-2 hrs later, cortisol decreases but still suppresses stress responses from initial phase; genomic action through GRs, effects can last for several hours, help to consolidate & preserve info about stressful event & renormalize brain
During what phase does cortisol factiliate hippocampus-dependent memory & learning?
adaptation phase, does depend on time of events however
If you have stress during a learning situation what is released and what does this facilitate?
releases NA, CRH & CORT
all facilitate ongoing process of perception & attention in initial phases of learning
What does cortisol have to do with gene-mediation?
initiates gene-mediated pathways which facilitates consolidation of relevant info & temporarily inhibits input of info unrelated to initial event
What happens if stress precedes learning?
gene-mediated suppression of activity will occur during acquisition of present learning task- cortisol impairs learning task & also inhibits recall later
What brain structure stimulates the HPA axis during stress?
amygdala
What does cortisol do to the amygdala during stress?
increases amygdala’s responses to stress by facilitating activation by NE
*NE & cortisol enhance amygdala activity in response to stress
What does acute stress cause to happen in the mPFC?
cortisol activates mPFC which improves working memory & helps terminate HPA stress response (mPFC projects activity to PVN)
What does greater stress cause to happen in the PFC?
high cortisol disrupts working memory & creates distractibility
What does chronic stress cause in the PFC?
down regulation of GR w/in mPFC w/ impaired negative feedback regulation by cortisol & enhanced HPA activity (hypercortisolism)
*excess cortisol leads to reduced top down PFC inhibition of amygdala
In order to mediate behavior to stress & to mediate sympathetic activation, what two parts of the brain are activated?
during stress, CRF neurons in BNST & amygdala help to mediate behavior & sympathetic activation associated w/stress
Does cortisol provide negative or positive feedback on CRF synthesis? What does this lead to?
increases synthesis of CRF= means for extending contribution of brain stress systems to allostasis
What are the two ways that chronic stress leads to increased cortisol?
- up regulation of VP: VP co-secreted w/CRH, facilitates release of ACTH, ACTH release becomes more dependent on VP & less on CRH; VP now less inhibited by cortisol feedback compared to CRH= increased cortisol release
- up regulation of ACTH receptors in adrenal= adrenal angiogenesis, hyperplasia & hypertrophy
Does hypercortisolism shift the body to be more or less sensitive to cortisol? How does this correlate to hippocampal negative feedback?
shifts the body to be less sensitive to cortisol= maintain higher cortisol levels
hippocampal negative feedback is less responsive & amygdalar positive feedback loop is more responsive= increase HPA activity= high cortisol levels reset HPA to maintain high cortisol
What is melancholic depression? What percentage of major depressive disorders does this category represent?
30% of MDDs
HPA axis hyperactivity & hypercortisolemia (higher CRH levels)
What is atypical depression? What percentage?
30% of MDDs
inflammatory & metabolic dysregulation= higher inflammatory markers, BMI, waist circumference & triglycerides; lower HDLs; hypersomnia, NORMAL CORTISOL, younger age of onset, females affected more
Which hormone is driven by acute stressors? by chronic ones? How does cortisol affect each?
CRH- acute stressors
AVP- chronic stressors
cortisol has negative feedback effect on CRH & ACTH but positive feedback effect on AVP release of ACTH
What are the two effects of increased ACTH?
- generates higher than normal levels of cortisol to cope w/ongoing stressor
- allows for increased production of cortisol where acute-on-chronic stress is required
Brain exposure to CRH & cortisol leads to what?
Brain exposure to cortisol and/or AVP leads to what?
CRH + cortisol= melancholic depression
cortisol w/ or w/o AVP= atypical depression
Are circadian fluctuations of cortisol flattened or exaggerated in chronic stress? How does this relate to sleep and cortisol & glucose levels?
flattened
CRH sensitivity to stressors reduced
sleep disruption elevates evening cortisol & glucose levels, insulin resistance
When do cortisol levels peak? When are they lowest?
peak hour or so after waking= decrease sensitivity of CRH secreting cells to cortisol in morning
lowest in early evening= increased sensitivity in evening
CRH, ACTH & cortisol high in morning, low at night
How long are ultradian rhythms?
60-90 mins
What does fasting do to cortisol levels?
enhance cortisol levels, modify circadian pattern by delaying blood cortisol concentrations to early afternoon
What are 3 diseases associated with high cortisol over long periods of time?
osteoporosis
insulin resistance
vascular disease
