Chronic Stress

Question 1

What characteristics define chronic stress?

Answer 1

Prolonged, severe, or uncontrollable.

Question 2

How does chronic stress dysregulate the HPA axis?

Answer 2

• Prolonged activation → increased CRF and cortisol release
• Desensitisation of glucocorticoid receptors (GRs)
• Impaired negative feedback → sustained cortisol elevation
• Leads to hippocampal atrophy and further HPA dysfunction

Question 3

How does HPA dysfunction differ in depression vs PTSD?

Answer 3

Depression:
• Constant HPA activation
• ↑ Baseline cortisol
• Impaired dexamethasone suppression
• ↓ GR sensitivity

PTSD:
• Enhanced HPA sensitivity
• ↓ Baseline cortisol
• Intact dexamethasone suppression
• ↑ GR sensitivity

Question 4

What are the neurobiological effects of chronic stress on the hippocampus?

Answer 4

• Atrophy, reduced dendritic branching and spine density

Question 5

What are the neurobiological effects of chronic stress on the amygdala?

Answer 5

• Hypertrophy, increased dendritic spines → heightened fear and HPA activation

Question 6

What are the neurobiological effects of chronic stress on the prefrontal cortex?

Answer 6

• Reduced dendritic spines → impaired regulation of emotion and stress

Question 7

What does hippocampal volume indicate in PTSD?

Answer 7

• Smaller hippocampus is a risk factor, not a consequence
• Twin studies show non-exposed twins of PTSD patients also have smaller hippocampi

Question 8

What is the controllable vs uncontrollable shock model?

Answer 8

• Escapable shock (ES): Mouse can terminate shock → resilience
• Inescapable shock (IS): No control → learned helplessness, increased fear, elevated cortisol
• IS mice show:
• ↑ Freezing in fear conditioning
• ↑ Immobility in forced swim test
• ↑ Corticosterone levels

Question 9

What is the chronic corticosterone model?

Answer 9

• Corticosterone administered in drinking water for ~20 days
• Mimics chronic stress exposure
• Causes:
• Depressive-like behaviour
• Impaired extinction
• Structural brain changes (e.g., hippocampal atrophy, amygdala hypertrophy)

Question 10

How do SSRIs modulate the stress response?

Answer 10

• Increase BDNF → promote hippocampal neurogenesis → restore HPA regulation

Question 11

How do benzodiazepines modulate the stress response?

Answer 11

• Reduce overall neural activity → acute anxiolytic effects

Question 12

How do beta-blockers modulate the stress response?

Answer 12

• Block NE → reduce physical symptoms of anxiety

Question 13

How does CBT modulate the stress response?

Answer 13

• Enhances prefrontal and hippocampal function → improves amygdala regulation

Question 14

What are emerging treatments targeting the HPA axis?

Answer 14

• CRH antagonists: Block HPA activation at the source
• BDNF (Brain-Derived Neurotrophic Factor) mimetics: Promote hippocampal growth and plasticity
• MDMA: Increases oxytocin → may counteract CRH and reduce stress reactivity