Lecture 14 Neuroimaging of Stress Flashcards
Stress response to maintain homeostasis and how it can be bad for you
Baboon experiment
Quasi experimental
Had good ecological validity
Allostatic load and why it is bad for you
It is bad if too much
Repeated stressor activation leads to higher allostatic load
HPA and SNS work in concert
Early exposure to stress leads to decreased negative feedback and hence increased HPA activation
Abused kids show lower HPA (and compensatory high SNS)
Causal direction unknown
Adaptation to stress
Should adapt to long term stress, if you so not (individual variation) you will get increased allostatic load
Primary consequences of allostatic load
Are direct mechanisms of the stress response
Serum DHEA-S
Overnight urinary cortisol
Overnight noradrenaline and adrenaline excretion
Secondary consequences of allostatic load
Are measures of the response to stress responses
Systolic and systolic BP
Waist-hip ratio
And index of the increased glucocorticoid activity
-adipose here is what is linked with heart issues
Sedum HDL and LDL
Linked with cholesterol damage
Blood plasma levels of glycosylated hemoglobin
Why stress is bad for you, the allostatic load hypothesis
Changes in stress lead to changes in physiology which in turn, lead to changes in disease
Is caused by allostatic load just like glucocorticoid cascades are
Why stress is bad for you, the allostatic load hypothesis
Linked systems that contribute
The environment
Individual differences (genes, development, experiences)
Perceived threats (life events, helplessness, vigilance)
Behavioral responses
ALL THESE LEAD TO
Physiological responses
These cause either allostasis and adaptation OR allostatic load and damage
Tertiary consequences of allostatic load
Disease caused by allostatic load
Psychological - Major Depressive Disorder
Physiological - CV disease, abdominal adiposity, bone loss
Co morbidity between MDD and CVD
If allostatic load is causal, there should be a relationship between the two things. There is!
- Onset of MDD predicts worse CVD
- LDL linked to adiposity, linked to CVD (putting on fat in torso)
- MI most common in the morning (at time of peak cortisol)
- CVD linked to decreases in bone density
It is all correlation but looks convincing
Why stress is bad for you
What the HPA and SNS activity to to help/hinder
Stress hormones are initially beneficial but detrimental long term
Chronic activation is a problem
Glucocorticoids (bind at GR)
- conversion of proteion and lipids to carbohydrates for energy
- Increase food seeking and locomotor activity
- gets you energy to cope with stress
SNS activation
- increase HR and BP
- Gets you up/gives you MI
Increased allostatic load = negative physiological effects
Why stress is bad for your brain
Stress can lead to vivid memory
- flashbulbs
- Good stressors make important memories stand out
Increased CRH in various brain regions following stress
Increases HPA
However
Prolonged activation downregulates receptors
Reduced negative feedback
Cell death in hippocampus
Is one of the first things seen in Alz for example
Also amygdala and frontal cortices
This effect can be seen in humans via imaging
In rats (management of proceptive HPA activation)
Inhibitory action on GABA neurons from Ventral Subiculum and PFC
Only inhibitory T2 neurons here
Gets shut off by circulating GC (so more HPA)
More activation of this = less inhibition of PVN = more HPA
Excitatory action on GABA from amygdala
More activation = more gaba
Why stress is bad for the brain (2)
Chronic stress increases the CRH in the amygdala
Contributes to HPA dysregulation and behavior
Experiment with CRH into rats
Inject via cannulation, CRH into amygdala 1x a day for 5 days
G1 injected
G2 not
G1 Trapped (restraint stressor) G2 Not (control)
2x2 design
ACTH and corticosterone measured
Grooming behaviour measured as a surrogate for the rat being stressed
Higher grooming = higher stress
In the non- chronically stressed (no injection) mice, there was no significant difference in those who were restrained or not in time grooming
In the chronically stressed group (injection) the retrained mice are extremely stressed and do significantly more grooming compared to non restrained ones
A BIGGER STRESS RESPONSE
(Chronic stress might enhance the stress response)
Also this group showed less corticosterone at baseline, after 15 mins this was equal between chronically stressed and control then then at 60 mins they had higher levels again
So higher levels at baseline (released from restrain stress)
Same after 15 mins
Higher after 60 mins (after restraint stress)
What effects can we se in human brains (via imaging)
Yes, imaging stress is critical to extend animal findings
Resolution is poor though
These experiments are guided by rat research as this shows them what region to image