Lecture 3 - The stress hypothesis of depression

Question 1

What are the 4 criteria for stress according to Toates (1995)?

Answer 1

1. Over time behaviour does not correct a disturbance (open loop)
2. Excessive activity in sympathetic branch and neurohormonal systems (HPA)
3. Animal becomes vulnerable to a certain pathology (e.g., depression)
4. Increased frequency of pointless behaviours (stereotypes)

Question 2

Study: Sapolsky’s baboons (1989,1990)

Answer 2

• Dominant baboon: low baseline cortisol, peaked when attacked
• Subordinate baboon: high baseline cortisol, prolonged elevated HPA activity

Conclusions:
- Groups ruled by dominant male who gets the best food and access to females
- Prolonged exposure to stress in subordinate males leads to depression, high baseline levels of cortisol and loss of negative feedback

Question 3

What is the stress hypothesis of depression?

Answer 3

• Chronic stress leads to depression
• Increased HPA activity = more cortisol
• Diminished negative feedback through loss of glucocorticoid receptors

Question 4

Stress hypothesis of depression: DIRECT evidence

Answer 4

• Nemeroff et al. (1995) - Adrenal gland enlarged in depressed patients
• Carroll et al. (1984) - Dexamethosone given to depressed and healthy PTs to temporarily stop release of cortisol and then given a dose of corticotrophin releasing hormone and cortisol measured

Question 5

Stress hypothesis of depression: INDIRECT evidence

Answer 5

• Sherwood-Brown et al. (2001): systemic corticosteroid treatment causes mood changes as a side effect
• Tang et al. (2013): Cushing’s syndrome is associated with symptoms of depression

Question 6

What is the role of CRH?

Answer 6

• Coordinates the stress response
• Increases NA
• Released in limbic (emotional) brain legions
• Injection of CRH increases fear and anxiety responses in animals
• Too much leads to imbalanced noradrenergic system, which puts the brake on serotonin 5-HT and reduces mood

Question 7

What are the neurotoxic effects of cortisol?

Answer 7

• Hippocampal damage
• Amygdala overactivity
• Cortical abnormalities

Question 8

What are three possible health conditions that result from damage to the hippocampus?

Answer 8

• Hypoxia
• Ischemia
• Hypoglycaemia

Question 9

Study: Uno’s vervet monkeys 1989

Answer 9

• Enlarged adrenals
• Gastric ulcers
• Hippocampal degeneration - CA1 field

Question 10

Study: Diamond et al. 1999

Answer 10

• 5-fold increase in cortisol
• Decreases cell firing in dentate gyrus
• Reduced learning