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Post Midterm Lecture Notes P1.pdf

Course Code
PSYC 342
Jens C Pruessner
Study Guide

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Lecture 11 - Feb. 16:
The HPA axis:
Hypothal mediate nervous information with endocrine information
oThe median eminence is located next to the hypothalamus -- one of the 3 entries from the periphery to the CNS (no
blood brain barrier)
Note pituitary is not part of the brain (hormones would have to exit via the median eminence)
oAnterior pituitary release ACTH binds to membrane receptor
oAdrenal gland synthesis and secretion of glucocorticoid
Glucocorticoids increases glucose metabolism (gluco-corti-coid: glucose-cortex-steroid)
Goes directly into cell
oIncrease neoglucogenesis
oActs on insulin to maintain glucose in the blood vessels
oEffects on brain and cognitive functions
oAffects the immune system
oPrevent overshoot of other systems
Thermoregulation: HPA activated when immune system goes into overdrive in trying to fight off infections
with a high fever
o**HPA axis needs to be tightly regulated as it prevents overshoot of other systems
Functional tests for the HPA axis
CRH injection: test for pituitary and adrenal response
ACTH injection
Dexamethasone: agonist of glucocorticoid receptor -- test for extent of negative feedback on the pituitary and the adrenal
oMuch more potent in activating the receptors
oBinds to pituitary and have huge negative feedback on pituitary
oDoes not cross blood brain barrier, no effect on CRH secretion
DEX/CRH injection:
oPurpose: to send mix signal to the body to test how robust the regulatory system is
oIf DEX receptors are good and present, pituitary will stop secreting ACTH momentarily due to huge negative
feedback --> even when CRH given after DEX, you still should not see any cortisol release
oIf cortisol release is seen, then there must be a problem with the GR (glucocorticoid receptors)
Baseline testing: Testing integrity of HPA axis
oCAR: cortisol awakening response peaks 30min after you wake up
oWhen exposed to chronic stress, there can be variation in the circadian rhythm
oCAR levels are used in conjunction with stressor test to show the baseline reactivity of the HPA axis (some people
have naturally lower cortisol response in general)
Stress test
oEcological valid way to access HPA axis
oReference paradigm for stress test: DSST -- giving speech in front of people -- a cortisol increase should be seen
In front of people who are very critical
5min to prepare for 5min speech
Mental calculation for 5min with people constantly telling you that you've got it wrong
oSocial stress
oOther physical stress tests: e.g. bike for an hour
Topic for today: applying stress tests to better access relation of HPA axis to certain psychopathologies
Issues: difficult to establish relation between the pathologies on the HPA axis.
It would be tempting to induce a causal effect (e.g. high stress response in depressed population, so because they are more
stressed, they are depressed) --> its just an association (correlation and not causation)
Psychopathologies with dysregulation of the HPA axis
Major depression
Childhood abuse
Posttraumatic stress disorder
Glucocorticoid cascade hypothesis
Symptoms: both psychological and physiological
Insomnia, oversleep
Lack of energy
Ruminative thoughts
Brain correlates of depression
Evidences from both human and animals (e.g. rat models)
Model of depression in animals:
Unpredictable chronic mild stress over 3-6 weeks -- approach symptoms seen in humans
e.g. anhedonia: no longer drink sugar water

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Neuroimaging evidences
Difference in brain structures between healthy controls and depressed patients
Region involved in stress regulation:
Prefrontal cortex
Hippocampus, amygdala
Hypothalamus and pituitary
Pre-genus ACC (arcuate cingulate cortex) -- highly associated with depression
More activated in depressed patients when given an affective task
Depression and CRH overdrive
Boosting the HPA axis induces anxiety related activates
Decreased: eating, sleeping, reproductive activities
Increased restless activity in familiar envt, withdrawal in unfamiliar envt
Depressed patients have overdrive of CRH in the cerebral spinal fluid
When they recover from depression, CRH levels goes back to normal
There seem to be a link of causation, but still ambiguous
Role of the amygdala
Fear and stress regulation
More activation in depressed population
Effects of childhood abuse on brains of depressive patients
Researcher from McGill -- effects of varying maternal behaviour over the development of the stress system
Organizational effect: Different maternal rat behaviour has influence over the organizational events in the HPA axis. When rats mature,
they have differing responses to stress
Study 1: by Christine Helm in Women
Dysregulation of HPA activity in depressed patients-- is it due to depression or is it early life trauma?

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Control group: no depression, no early life trauma (physical or sexual abuse)
Group 2: trauma but no depression
Group 3: trauma and depression
Group 4: just depression
ACTH: highest increase is depression + trauma, next is trauma without depression
Pituitary is more sensitive in people who have experienced trauma
Overdrive of CRH in people with early life trauma
Cortisol: increase in those with depression and trauma -- so the increase is mostly due to depression
Heart Rate (related to SNS, which is another stress response system): increase in those with depression and trauma
Early trauma --> dysregulation of ACTH --> possibly increasing susceptibility to developing depression
If you do get depression --> further dysregulation of cortisol and heart rate
Study 2 by Helm with men
Administered the DEX CRH test. On healthy controls, Pitutiary should not have ACTH at all with DEX injection
Then given CRH:
People with depression and trauma has a greatest increase in CORT levels --> dysregulation of the pituitary
Not enough cortisol receptors to block the CRH release even though the pituitary is full of DEX
People with early life trauma also has higher CORT levels than controls
Cortisol acts on glucocorticoid receptor. DEX has much higher binding affinity. But its effects on only on ACTH and cortisol.
Fully functional system: no ACTH at all
By stressing the system even more with administration of CRH: if ACTH is still released, the system could be:
Insufficient GR to effect on a DEX signal OR
Hypersensitive to CRH (more likely)
Study 3
CSF spinal tap to get level of CRH
Level of CRH associated with the level of physical abuse: different types of abuse and different ages of onset
Looking at different critical periods/sensitive time windows where the organizational effect/programming effect takes place
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