Cortisol + CCK

Question 1

Q1. What is a neuropeptide? Explain from first principles.

Answer 1

A neuropeptide is a chemical messenger used by neurons that is made of amino acids linked together (so it is protein-like).

Neuropeptides are:

• Synthesised in the neuronal cell body (not at the synapse)
• Packaged in dense-core vesicles * Released when neurons fire repeatedly or strongly
• Used to modulate brain activity rather than produce fast on–off signals. The key idea is that neuropeptides do not cause immediate excitation or inhibition. Instead

Question 2

Q2. How are neuropeptides different from classical neurotransmitters?

Answer 2

Classical neurotransmitters like dopamine or GABA act quickly

Question 3

Q3. Why are neuropeptides important in psychiatry?

Answer 3

Psychiatric symptoms involve mood

Question 4

Q4. What is corticotrophin-releasing hormone (CRH)?

Answer 4

CRH is a neuropeptide produced in the hypothalamus

Question 5

Q5. What is the HPA axis? Explain step by step.

Answer 5

The HPA axis is the hypothalamic–pituitary–adrenal axis

Question 6

Q6. Does CRH only act via hormones?

Answer 6

No. CRH has two roles: • A hormonal role

Question 7

Q7. How does CRH lead to cortisol release? (Mechanism of action)

Answer 7

CRH binds to CRH-1 receptors on corticotroph cells in the anterior pituitary. These receptors are G-protein-coupled receptors

Question 8

Q8. What does cortisol normally do?

Answer 8

Cortisol is a short-term survival hormone. Its normal effects include raising blood glucose

Question 9

Q9. What is negative feedback in the HPA axis?

Answer 9

Negative feedback means that cortisol binds to glucocorticoid receptors in the hypothalamus

Question 10

Q10. What is dexamethasone?

Answer 10

Dexamethasone is a synthetic glucocorticoid. It acts like cortisol but is more potent at activating glucocorticoid receptors

Question 11

Q11. What is the dexamethasone suppression test?

Answer 11

The dexamethasone suppression test (DST) assesses whether the HPA axis responds normally to negative feedback. Dexamethasone is given (usually at night)

Question 12

Q12. What is the normal response to dexamethasone?

Answer 12

In a healthy system: dexamethasone activates glucocorticoid receptors

Question 13

Q13. What is dexamethasone non-suppression and what does it mean?

Answer 13

Dexamethasone non-suppression means cortisol levels remain high despite dexamethasone. This indicates impaired glucocorticoid receptor feedback and a hyperactive HPA axis. 🔥 Exam association: Major depressive disorder.

Question 14

Q14. What happens to CRH and cortisol in major depression?

Answer 14

In major depression: CRH levels are increased

Question 15

Q15. How does raised cortisol produce depressive symptoms?

Answer 15

Chronically raised cortisol disrupts sleep

Question 16

Q16. What happens to CRH and cortisol in anxiety disorders?

Answer 16

In anxiety disorders: central CRH activity is increased while cortisol levels may be normal or mildly elevated. Symptoms are driven more by CRH and noradrenergic arousal than by cortisol. ⚠️ Exam trap: Anxiety does not always mean high cortisol.

Question 17

Q17. What happens to CRH and cortisol in PTSD?

Answer 17

PTSD shows a distinctive pattern: central CRH activity is increased

Question 18

Q18. Why does low cortisol worsen PTSD symptoms?

Answer 18

Cortisol normally inhibits amygdala activity

Question 19

Q19. What is the single best way to summarise CRH pathology across disorders?

Answer 19

• Depression: high CRH

Question 20

Q1. What is cholecystokinin (CCK)?

Answer 20

Cholecystokinin (CCK) is a neuropeptide that acts as both a gut hormone and a central nervous system neuropeptide. It is involved in regulation of satiety

Question 21

Q2. Why is CCK relevant to psychiatry?

Answer 21

CCK is one of the most anxiety-provoking neuropeptides in the brain. It is directly involved in panic attacks

Question 22

Q3. Where is CCK produced?

Answer 22

CCK is produced in the gastrointestinal tract (released from the small intestine

Question 23

Q4. Where does CCK act in the brain?

Answer 23

CCK acts in the amygdala

Question 24

Q5. What receptors does CCK act on?

Answer 24

CCK-A receptors (mainly gut

Question 25

**Q6. What does CCK normally do in the gut?**

Answer 25

In the **gastrointestinal system**

Question 26

**Q7. What does CCK do in the brain?**

Answer 26

In the **brain**

Question 27

**Q8. How does CCK cause anxiety and panic? (Mechanism of action)**

Answer 27

**CCK** binds to **CCK-B receptors** (highly expressed in the **amygdala**)

Question 28

**Q9. What is the evidence linking CCK to panic disorder?**

Answer 28

**CCK infusion** causes **mild anxiety in healthy individuals** but **full panic attacks in panic disorder**. 🔥 **Exam GOLD PHRASE:** **“CCK infusion reliably provokes panic attacks in panic disorder.”**

Question 29

**Q10. What does this tell us about panic disorder?**

Answer 29

**Panic disorder** involves **hypersensitivity of CCK-mediated fear circuits** and **dysregulation of neuropeptide-based anxiety signalling** — a **disorder of fear physiology**.

Question 30

**Q11. How is CCK different from CRH in anxiety?**

Answer 30

**CCK** = **acute**

Question 31

**Q12. How does CCK interact with dopamine?**

Answer 31

**CCK** is **co-released with dopamine** in **mesolimbic pathways**

Question 32

**Q13. How does CCK affect appetite and why is this relevant to psychiatry?**

Answer 32

**CCK reduces appetite** via **early satiety** and **visceral sensations**

Question 33

**Q14. What psychiatric disorders are linked to CCK?**

Answer 33

**CCK** is linked to **panic disorder**

Question 34

**Q15. What are the most common MRCPsych Part A exam traps with CCK?**

Answer 34

Common errors: **thinking CCK increases appetite**

Question 35

**Q16. What is the single best one-sentence exam answer for CCK?**

Answer 35

**Cholecystokinin** is a **gut–brain neuropeptide** that promotes **satiety** and via **central CCK-B receptors in the amygdala** lowers the **panic threshold**