Cranial nerves > Orexin > Flashcards

Orexin Flashcards

(49 cards)

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1
Q

What is orexin?

A

Orexin is a neuropeptide that:
- Promotes wakefulness (arousal)
- Stabilises the sleep–wake switch
- Increases alertness
- Increases motivation
- Increases reward drive
- Links energy balance with arousal

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2
Q

What peptides make up the orexin system?

A

The orexin system consists of:
- Orexin A
- Orexin B

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3
Q

What is another name for orexin?

A
  • Orexin is also called hypocretin
  • Older literature uses the term hypocretin
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4
Q

Where is orexin produced?

A

Orexin is produced:
- In one small area only
- In neurons of the lateral hypothalamus
- By a small population of neurons
- With very widespread projections

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5
Q

What is the classic exam phrase describing orexin neurons?

A
  • Orexin neurons are few in number
  • But project diffusely throughout the brain
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6
Q

Where does orexin act in the brain?

A

Orexin neurons project to:
- Locus coeruleus (noradrenaline)
- Dorsal raphe nucleus (serotonin)
- Tuberomammillary nucleus (histamine)
- Ventral tegmental area (VTA) (dopamine)
- Basal forebrain (acetylcholine)
- Cerebral cortex (wakefulness)

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7
Q

What is the overall organisational role of orexin in the brain?

A
  • Orexin acts as the conductor of the arousal orchestra
  • It coordinates monoaminergic arousal systems
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8
Q

What receptors does orexin act on?

A

Orexin acts on:
- OX1 receptor
- OX2 receptor
Both are:
- G-protein coupled receptors (GPCRs)

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9
Q

What happens at the cellular level when orexin binds its receptor?

A

Orexin receptor activation causes:
- Increased intracellular calcium
- Neuronal depolarisation
- Increased firing of arousal neurons
Net effect:
- Activation of wake-promoting systems

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10
Q

Is orexin excitatory or inhibitory?

A
  • Orexin is excitatory
  • It promotes neuronal firing
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11
Q

What is the primary physiological role of orexin?

A

The main role of orexin is:
- Stabilisation of wakefulness
- Prevention of inappropriate sleep
- Prevention of REM sleep intrusion

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12
Q

What is the sleep–wake flip-flop switch?

A

The sleep–wake system:
- Has sleep and wake systems that inhibit each other
- Is inherently unstable
- Requires stabilisation to prevent sudden switching

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13
Q

How does orexin affect the sleep–wake switch?

A

Orexin:
- Stabilises the sleep–wake switch
- Keeps wakefulness continuous
- Prevents REM intrusion into wakefulness

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14
Q

What is the classic exam association of orexin loss?

A
  • Narcolepsy
  • Especially narcolepsy with cataplexy
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15
Q

What is the core pathology in narcolepsy?

A

Narcolepsy is caused by:
- Loss of orexin-producing neurons
- In the lateral hypothalamus

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16
Q

What happens to orexin levels in narcolepsy?

A
  • Orexin levels are low or absent
  • Especially low in CSF
  • Most evident in narcolepsy with cataplexy
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17
Q

Why does loss of orexin cause excessive daytime sleepiness?

A

Without orexin:
- Arousal systems fire inconsistently
- Wakefulness cannot be maintained
- Alertness becomes fragmented

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18
Q

Why does loss of orexin cause REM intrusion?

A

Loss of orexin:
- Removes stabilisation of wakefulness
- Allows REM sleep features to intrude into wakefulness

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19
Q

What symptoms are explained by REM intrusion in narcolepsy?

A

REM intrusion causes:
- Cataplexy
- Sleep paralysis
- Hypnagogic hallucinations
- Sleep attacks

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20
Q

Is narcolepsy a general hypothalamic failure?

Study These Flashcards
A
  • No
  • It involves selective loss of orexin neurons
  • Other hypothalamic neurons are preserved
21
Q

What role does orexin play in arousal and attention?

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A

Orexin:
- Maintains alertness
- Increases sustained attention
- Prevents drowsiness

22
Q

Why is orexin relevant to psychotropic sedation?

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A
  • Many psychotropics reduce arousal
  • Orexin is part of the final common arousal pathway
  • Reduced orexin signalling increases sedation vulnerability
23
Q

How does orexin affect motivation and reward?

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A

Orexin:
- Activates VTA dopamine neurons
- Increases motivation
- Increases goal-directed behaviour
- Increases reward seeking

24
Q

Which psychiatric domains are linked to orexin and reward?

Study These Flashcards
A

Orexin is linked to:
- Motivation
- Drive
- Addiction biology
- Reward processing

25
**Is orexin primarily an appetite hormone?**
- No - Appetite effects are **secondary** - Orexin’s primary role is **arousal**
26
**How does orexin normally relate to appetite?**
Normally: - Energy deficit increases orexin - Wakefulness increases - Motivation to seek food increases Orexin links **energy deficit** to **arousal and food-seeking**
27
**How does narcolepsy affect body weight?**
In narcolepsy: - **Weight gain is common** - Occurs **without increased appetite**
28
**Why does weight gain occur in narcolepsy?**
Weight gain occurs due to: - Reduced **energy expenditure** - Reduced **physical activity** - Reduced **sympathetic tone** - Altered **dopamine–metabolism balance**
29
**Does orexin loss cause overeating?**
- No - Weight gain is due to **low energy expenditure** - Not due to **hyperphagia**
30
**What is the key exam phrase about weight gain in narcolepsy?**
- Weight gain in narcolepsy is due to **reduced energy expenditure** - Not increased appetite
31
**One-sentence MRCPsych Part A summary of orexin**
**Orexin (hypocretin)** is a lateral hypothalamic neuropeptide that stabilises wakefulness by activating widespread arousal and reward systems, and its loss causes narcolepsy with REM intrusion and weight gain due to reduced energy expenditure rather than increased appetite.
32
33
**Why is orexin relevant to psychiatry?**
Orexin links: - **Sleep–wake regulation** - **Arousal & alertness** - **Motivation & reward** - **Energy balance** - **Stress & anxiety** These domains are central to **psychiatric symptoms** and **psychotropic effects**.
34
**Which psychiatric symptoms are most directly linked to orexin?**
Symptoms linked to orexin dysfunction: - **Excessive daytime sleepiness** - **Fragmented wakefulness** - **REM intrusion phenomena** Especially relevant in **narcolepsy**.
35
**What is the key sleep disorder associated with orexin loss?**
Key disorder: - **Narcolepsy** (especially **with cataplexy**) Core mechanism: - Loss of **hypothalamic orexin neurons** - **Unstable sleep–wake switch**.
36
**How does orexin explain cataplexy (psychiatric framing)?**
Mechanism: - Orexin normally **prevents REM sleep during wake** - Loss allows **REM atonia to intrude into wakefulness** - Often triggered by **emotions** (laughter, surprise) Result: - **Sudden muscle weakness** without loss of consciousness.
37
**Why is narcolepsy sometimes misdiagnosed as a psychiatric disorder?**
Because patients may present with: - **Fatigue** - **Poor concentration** - **Emotional lability** - **Hypnagogic hallucinations** Exam trap: - These are **REM-related phenomena**, not psychosis or depression.
38
**What role does orexin play in arousal?**
Orexin: - Activates **monoaminergic arousal systems** - Maintains **sustained alertness** Loss leads to: - **Sleepiness** - **Fatigue** - **Poor attention**.
39
**How is orexin relevant to psychotropic sedation?**
Psychotropic relevance: - Many drugs **reduce arousal** - Orexin is part of the **final common arousal pathway** Therefore: - **Reduced orexin signalling** → greater **sedation vulnerability**.
40
**How does orexin relate to motivation?**
Orexin: - Activates **dopamine neurons** in the **VTA** - Increases: - **Drive** - **Goal-directed behaviour** - **Effortful motivation** Loss causes: - **Apathy** - **Low drive** - **Reduced initiative**.
41
**What psychiatric symptom cluster resembles low orexin activity?**
Low orexin activity resembles: - **Fatigue** - **Low motivation** - **Reduced alertness** - **Reduced reward sensitivity** Overlap: - **Depressive phenomenology** (arousal-based mechanism).
42
**How does orexin relate to addiction biology?**
Orexin: - Facilitates **reward-seeking behaviour** - Activates **mesolimbic dopamine pathways** Psychiatry relevance: - Links **arousal**, **motivation**, and **reward seeking**.
43
**What is orexin’s role in stress states?**
Orexin: - Increases **sympathetic tone** - Promotes **hyperarousal** Associated with: - **Alertness** - **Vigilance** - **Stress-related arousal** Seen in **anxiety states**.
44
**Is orexin mainly an appetite hormone?**
No: - Orexin’s **primary role is arousal** - **Appetite effects are secondary**.
45
**How does orexin loss affect weight in narcolepsy?**
Effects: - **Weight gain is common** - Occurs **without increased appetite** Mechanisms: - **↓ Energy expenditure** - **↓ Physical activity** - **↓ Sympathetic tone** Exam trap: - Weight gain ≠ **hyperphagia**.
46
**How is orexin different from leptin (psychiatry focus)?**
Key differences: - **Orexin**: arousal, wake stabilisation, **narcolepsy** - **Leptin**: energy sufficiency, appetite regulation, **obesity/anorexia** Loss of orexin → **sleepiness** Loss of leptin signalling → **starvation signals**.
47
**What is the classic MRCPsych exam trap involving orexin?**
Incorrect: - “**Orexin is mainly a feeding hormone**” Correct: - Orexin primarily regulates **wakefulness and arousal**.
48
**What is the one-sentence psychiatry summary of orexin?**
Orexin is a **hypothalamic neuropeptide** that stabilises **wakefulness**, supports **motivation and reward**, and whose loss causes **narcolepsy** with psychiatric-like symptoms such as fatigue, hallucinations, and emotional lability.
49
**What are the five key Part A takeaways for orexin?**
Key points: - Orexin links **sleep, arousal, motivation, reward** - Loss causes **narcolepsy**, not depression or psychosis - Many symptoms are **REM intrusion phenomena** - Weight gain due to **low energy expenditure** - Orexin ≠ appetite hormone (primary role = **wakefulness**).
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