Lecture 11 Stress Basics Flashcards
Three physiological stress systems
- Parasympathetic Nervous system
- Sympathetic Nervous system
- Hypothalamus-Pituitary Adrenal Axis (HPA)
Nor =
in the CNS (for the purposes of this course)
CNS vs HPA
CNS is much faster
HPA lasts longer
SNS
Spine > Medulla > Adrenaline
The Hypothalamus Pituitary Adrenal Axis: Major stress axis of the organism
HPA axis is relevant to stress
CNS > Hypothalamus > CRH > Anterior pituitary > ACTH > Adrenal Cortex > Free cortisol
Has a third order feedback loop that limits it
Free vs. Bound Cortisol
- CBG is a binding globulin
- Binds steroid hormones
- Regulates the amount that can bind to receptors
Hence we are mostly interested in FREE CORTISOL levels
Characteristics of the HPA
There is a baseline level of HPA activity
-Every 60-90 mins there is a pulse timed via negative feedback
Ultradian rhythm =more than once per day
When there is psychological stress = additional secretory burst
Circadian rhythm
daily pattern, nadir around midnight
peak in the morning to help us get up
Third Order feedback loop
like the HPG axis we know and love
Functional Tests of The HPA Axis
5 tests
(1) CRH
(2) ACTH
Both stimulate the system to increase cortisol
-Cannot cross the BBB but can cause Cortisol release via the adrenal cortex
-This can cross the BBB and exert negative feedback
-If these are administered constantly, they will overwhelm negative feedback
(3) Dexamethasone
Metabolite of cortisol
Decreases pituitary activity
(4)Combined DEX / CRH
Stimulates ACTH and inhibits - this tells you about pituitary function
-baseline (circadian rhythm) testing
-Do in AM at wake before stressors exert an influence
(5) Stress test
Lab controlled, standard stressor
-Watch the HPA axis
Glucocorticoid receptors (GCs) : DISTRIBUTION
Both types:
- Present in hippocampus
- Present in amygdala
- Present in hypothalamus
- Present in pituitary
Type 1
-Provides positive feedback
Not present elsewhere in the cortex
Type 2
-Provides negative feedback
Present in high concentrations in cortex, especially the frontal lobes
The balance of these receptors determines the effect inn the 4 common regions. Outside this, always has inhibitory effects
Processive vs systematic
Neurons in hippocampus, amygdala, frontal cortex, hypothalamus, brainstem
-projections to hypothalamus to regulate HPA
Differentiate processive vs systematic stressors: how fast is response needed?
- Ether hypoxia immediate (systemic)
- Midterm not death inducing (processive)
Systematic direct activation
Processive indirect effects
through GABA modulation
Systematic direct activation
Brainstem
Something life threatening e.g. hypoxia Does not need appraising Pain/hot/cold/hypoxia PVN > Increased HPA activity Direct excitation
Processive indirect effects
through GABA modulation
GABA neurons in the Preoptic area and the Hypothalamus have inhibit the PVN
These neurons:
(1) Receives excitatory input from the Ventral Hippocampus and PFC
- Increases the activity of GABA neurons
- Therefore indirectly excites the HPA axis
- More stress = more inhibition of the cortex and so less excitation of the GABA neurons
- More stress at the PVN
(2) Receives Inhibitory input from the amygdala
- When this activity is high, less GABA activity and therefore less inhibition of the PVN
- More stress
Type 2 GC receptors
- Are in the cortex
- More circulating cortisol leads to more inhibition of the cortex’s excitatory effect on the POA of the hypothalamus.
- This area has GABA projections to the PVN
- This lack of cortical situation drops the activity of the GABA neurons
- Hence activity at the PVN increases
So there is more stress
Lazarus: Primary / secondary appraisal
Stress can be good or bad
Demand > Resources: stress (distress)
-This type of stress is bad
Resources > Demand: challenge (eustress)
-This type is good (i.e. prep for midterm)
The stress appraisal theory
Environmental event is appraised
Primary - based on past XP and beliefs > threat or challenge or Benign
If benign, ignore
If threat go to secondary appraisal
Secondary appraisal
-What resources, options and effectiveness do I have
-Do I have enough
Perception matters here
Decide how to act (or not!)
Biopsychosocial model of stress
Extended Lazarus work
2 stress responses and interaction with perception
Events perceived as challenge or threat?
Challenge (DemandsResources): SNS adrenalin, HPA cortisol
Avoidance (Demands>Resources so ignore): SNS not activated, HPA extended activation
Threat/Challenge/Chronic threat system responses
Threat
(Demands exceed resources)
HPA + SNS activation
Challenge
(Demands do not exceed resources)
HPA not activated
SNS activated
Chronic Threat
(Demands chronically exceed resources)
HPA super activated
SNS not
(Might avoid a problem in this case)
Chronic stress
If chronic, HPA becomes hyperactivated while SNS no longer active
-Blood pressure remains elevated
Blood glucose elevated
-Believed to cause tissue and organ damage
Associated with Psychopathology (e.g., Depression)
- Future theories added individual differences
- Adaptive callibration model in reading
Scientific evidence for the models
Challenging to collect data
- Stress and resources are subjective
- A “standard” stressor can be interpreted in many ways
- Linking early life stress (organization) to current response (activation)
Problems:
Laboratory vs. real-life stressors
Stress markers
Coherence of stress responses among systems and with experience of stress
(do physiological measures map onto subjective ones?)
WHAT DO YOU MEASURE!
Laboratory versus real-life stressors: the Trier Social Stress Test
(1) Public speaking
(2) Doing math out loud with people watching and judging
HPA axis response - fast ACTH increase, slower cortisol increase
Necessary measures include…
3 types of thing
(1) Measures of HPA activity:
CRH, ACTH, Cortisol (Corticosterone)
(2) Measures of SNS activity:
Adrenaline, Noradrenaline, Alpha-amylase (metabolite of adrenaline), Heart rate variability
(3) Measure of subjective stress
Survey/questionnaires
Coherence among stress systems
At a stressor, there is an immediate spike in SNS activity
- This drops off over 10 mins
- Cortisone is slower to increase
- Peaks at 22 mins
- The SNS measures are dropping when COrtisol is peaking
Do the two systems add or are the compensatory for one another (Study 1 - dexa)
(Study 1)
- Dexamethasone suppresses HPA
- G1 Dexa G2 Control
- Do TSST
SNS (HR)
In control = activates
In G1 MASSIVE activation
HPA (Cortisol)
In control = activates
In G1 = no activation
Subjective Stress
In control = rise
In G1 = Very big rise
Conclusion
When HPA inhibited, SNS compensates and this is what drives subjective stress
Do the two systems add or are the compensatory for one another (Study 2 - propanolol)
G1 Propranolol (drops SNS) Control - nothing
SNS
G1 - no activation
Control - normal
HPA
G1 Large increase
Control - normal
Subjective stress
G1 - lower subjective stress
Control - normal
Conclusion
When SNS is dropped, HPA compensates by cos SNS is what drives subjective stress this is lower when SNS s inhibited
Coherence among stress systems: individual differences
Examine cortisol amylase and early life exposure to stressors
-Parental Bonding Inventory and Childhood Trauma Questionnaire Trier Inventory of Chronic Stress
Took only participants scoring higher than specific cut-off
Relationship between ELA and the response of stress system
Administered the Trier Social Stress Test
RESULTS
There was higher A Amlysae (SNS) in high Early Life Event groups
In Low ELA = normal
The ratio Amylase-Over-Cortisol shows this most accurately
Low cortisol activation in high ELA groups
Blunted Cortisol Response
In response to ELA the bodies stress system is organized differently and you see a lower Cortisol response to stress lifelong
We do not know in what direction (does this cause high SNS and so low HPA or the other way around)
AOC
AOC correlates with many aspects of chronic stress
Better than sAA Cort, or COA
Coherence among stress systems: individual differences
Supports complimentary stress theories
There is still evidence for additive ones too
AOC correlates with many aspects of chronic stress
Better than sAA Cort, or COA
New measure of bio stress that correlates with psyc stress so use this
ELA leads to blunted HPA because of high SNS activation or other way around
Glucocorticoid cascade hypothesis
Allostasis is the maintenance of homeostasis via change
-It has a price
Allostatic load (glucocorticoid cascade)
- The physiological cost of increasing and decreasing stress all the time
- Influenced by many things (such as genes/individual differences)
- Looked at stress and ageing
- Chronic stress leads to overactivation of receptors
- Get downregulated
- Negative feedback has less receptors to act on
- So cortisol levels increase
What follows? Immunosuppression, muscle atrophy, osteoporosis, hyperglycemia, atherosclerosis, diabetes
The insensitivity causes a viscous circle
Supposed to be mediated via HPA axis activity
neurotoxic effects of glucocorticoids in the brain
The glucocorticoid cascade hypothesis:
Cell damage in the CNS?
Glucocorticoids cross cell membranes and change protein production
Some repress growth factors
Some increase apoptotic factors
These combined lead to increased apoptosis
Proposed mechanisms of damage:
modulation of mRNA
inhibition of glucose transport
potentiation of excitatory amino acids
However, hippocampal ‘loss’ even in Cushing’s is reversible
no higher AD incidence after hypercortisolemia
So you can recover
