GC165 I Can’t Fall Asleep Sleep Physiology And Sleep Disorders
Sleep physiology encompasses the neurobiological mechanisms regulating the sleep-wake cycle, including circadian and homeostatic processes, while sleep disorders such as insomnia, narcolepsy, and obstructive sleep apnea represent disruptions in these processes leading to impaired sleep initiation, maintenance, or quality.
Sleep Physiology and Sleep Disorders (GC 165)
This lecture by Dr. KF Chung (HKU Psychiatry) covers the fundamental physiology of sleep and the major sleep disorders you will encounter clinically. It is a "bread-and-butter" psychiatry lecture that integrates neuroscience (circadian rhythm, neurotransmitters, sleep architecture), clinical psychiatry (insomnia, narcolepsy, parasomnias), respiratory medicine (obstructive sleep apnoea), and pharmacology (Z-drugs, CBT-I). For exams, this lecture commonly yields questions on: the two-process model, sleep architecture, DSM-5 insomnia criteria, the 3P model, narcolepsy tetrad, OSA diagnosis/severity grading, NREM vs REM parasomnia differentiation, and pharmacology of Z-drugs.
Learning Objectives (from lecture slide): [1]
- Learn the basics of sleep physiology
- Learn the diagnosis and treatment of some common sleep disorders
How this fits into clinical practice: A patient saying "I can't fall asleep" is one of the commonest complaints in primary care, psychiatry, and general medicine. The clinician must distinguish primary insomnia from comorbid insomnia (depression, anxiety, pain, OSA), identify red flags for narcolepsy or REM sleep behaviour disorder (neurodegeneration risk), and institute appropriate stepped-care management.
1. Sleep Physiology
"Sleep is a normal physiological drive. All animals even single-cell organisms have a rest-activity cycle but the timing, amount and type of sleep vary dramatically across species." [1]
Why this matters: Sleep is not a luxury or a learned behaviour — it is biologically conserved. Understanding this prevents you from dismissing sleep complaints as trivial.
"Sleep is a reversible behavioral state of perceptual disengagement from and unresponsiveness to the environment. Sleep is associated with a typical pattern of physiological and behavioral processes." [1]
Key words for exam: reversible, perceptual disengagement, unresponsiveness. This distinguishes sleep from coma (not easily reversible) and from anaesthesia (pharmacologically induced).
High Yield — Two-Process Model
"Two-process model. Circadian rhythm (Process C) is governed by the suprachiasmatic nucleus and under control by a set of clock genes. Key neurotransmitter is melatonin. Sleep-wake homeostasis (Process S) is a product of a complex network of brain regions and neurotransmitter pathways, which control sleep onset and maintenance. Key neurotransmitter is adenosine." [1]
| Feature | Process C (Circadian) | Process S (Homeostatic) |
|---|---|---|
| Structure | Suprachiasmatic nucleus (SCN) of hypothalamus | Complex network of brain regions |
| Key neurotransmitter | Melatonin | Adenosine |
| Mechanism | Internal biological clock ~24h, entrained by zeitgebers (light, temperature, social cues) | Accumulation of sleep-promoting substances with prolonged wakefulness |
| Peak sleepiness | ~3 am (major) and ~3 pm (minor) | Increases linearly with wakefulness; dissipates with sleep |
| Clinical relevance | Circadian rhythm disorders (DSWPD, jet lag, shift work) | Caffeine blocks adenosine receptors → promotes wakefulness |
Why adenosine? During wakefulness, neurons consume ATP. Adenosine is a metabolic by-product. It accumulates extracellularly and acts on A1/A2A receptors → inhibits wake-promoting neurons → promotes sleep drive. This is why caffeine (adenosine receptor antagonist) keeps you awake. [1][2]
Why melatonin? The SCN receives light input via the retinohypothalamic tract. In darkness, SCN signals the pineal gland to secrete melatonin, which feeds back to SCN receptors (MT1/MT2) and promotes sleep onset. Light suppresses melatonin → this is why bright light therapy works for circadian disorders and why evening blue light exposure from screens can delay sleep. [1]
"Process C: 2 peaks of sleepiness at 3pm and 3am. Process S: accumulation of sleepiness." [1]
Neuro-pathway regulating circadian rhythm: Retina → retinohypothalamic tract → SCN → superior cervical ganglion → pineal gland → melatonin secretion. Lesioning the SCN in animal studies results in sleep occurring throughout 24 hours (loss of consolidated sleep-wake pattern). [1]
"An animal study showing the result of lesioning suprachiasmatic nuclei. Sleep occurs throughout 24 hours." [1]
Free-running experiments: When subjects are removed from time cues, their sleep-wake cycle persists but drifts to slightly longer than 24 hours (typically ~24.2h). This proves the endogenous clock exists but requires entrainment by zeitgebers. [1]
High Yield — Sleep Stages and Architecture
"NREM & REM Sleep. NREM: Stage 1 to 4. Cycles every 90 mins. Stage 1 (2-5%); Stage 2 (45-55%); Stage 3 & 4 (13-28%); REM (20-25%); Wake ( < 5%). REM latency: 90 min. Shortened REM latency in depression (sleep phase delay hypothesis)." [1]
For sleep staging, EEG, EOG, and EMG are required [1] — this is the basis of polysomnography.
| Stage | % of Sleep | EEG Features | Key Points |
|---|---|---|---|
| NREM Stage 1 | 2-5% | Low-voltage mixed-frequency, theta waves | Lightest sleep; transition from wakefulness; easy to arouse |
| NREM Stage 2 | 45-55% | Sleep spindles (12-14 Hz bursts), K-complexes | Largest proportion of sleep; body temp drops, HR slows |
| NREM Stage 3/4 | 13-28% | High-amplitude slow waves (delta, < 2 Hz) | Deep sleep / slow-wave sleep (SWS); hardest to arouse; growth hormone release; predominates in first half of night |
| REM | 20-25% | Low-voltage, fast, desynchronized (resembles wake) | Dreaming sleep; muscle atonia; rapid eye movements; predominates in second half of night |
"Sleep goes from NREM Stage 1, to 2, 3, 4 then REM (regarded as 1 NREM-REM cycle), then goes back to NREM Stage 1 and repeat itself. More NREM Stage 3 & 4 (deep sleep) in first half and more REM (dreaming sleep) in second half." [1]
Why does this distribution matter clinically?
- Parasomnias arising from NREM (sleepwalking, night terrors) tend to occur in the first half of the night when deep sleep predominates.
- Parasomnias arising from REM (RBD, nightmares, sleep paralysis) tend to occur in the second half when REM predominates.
- Depression classically shows shortened REM latency (REM appears earlier than 90 min), increased REM density, and decreased SWS. [1]
Age-related changes: [1]
- "More deep sleep" in young adults → "More broken sleep" in elderly
- With ageing: decreased total sleep time, decreased SWS, increased awakenings, increased Stage 1/2, more fragmented sleep. This is a normal physiological change but predisposes elderly to insomnia complaints.
"Sleep deprivation has serious effects on experimental animals… became weak and uncoordinated and lost the ability to regulate body temperature… metabolic rates became so high that they continued to lose weight." [1]
"Partial sleep deprivation and short sleep duration ( < 7 hrs vs. 7-8 hrs) is associated with mental and physical health risks, e.g., cardiometabolic diseases. Long sleep duration ( > 9 hrs) also has health risks." [1]
This is a U-shaped relationship: both short and long sleep durations are associated with increased mortality, cardiovascular disease, diabetes, and cognitive decline. The "sweet spot" is roughly 7-8 hours for most adults.
"Your sleep need is determined by sleeping and waking in a free-running manner for at least 1 week… If you feel tired or sleepy in the daytime, you haven't slept enough." [1]
"History taking, Physical and mental state examination, Blood test and imaging studies, Sleep investigation." [1]
2.1 Sleep Investigations
| Investigation | What It Measures | When to Use |
|---|---|---|
| Subjective scales — Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS) | Self-reported severity of insomnia/sleepiness | Screening and monitoring |
| Sleep diary | Bed/wake times, sleep latency, awakenings, naps over 1-2 weeks | Insomnia, circadian disorders |
| Actigraphy (wearable device) | Rest-activity/sleep-wake patterns over days to weeks | Circadian rhythm disorders, insomnia assessment |
| Full-night Polysomnography (PSG) | EEG, EOG, EMG, airflow, respiratory effort, SpO2, ECG, leg EMG | Gold standard for OSA, narcolepsy, RBD, PLMD |
| Multiple Sleep Latency Test (MSLT) | Mean sleep latency across 4-5 naps at 2h intervals | Objective measure of sleepiness; narcolepsy diagnosis |
| Salivary dim light melatonin onset (DLMO) | Timing of melatonin rise | Circadian rhythm disorders |
"Pathological sleepiness: mean sleep latency < 5 min." [1]
Epworth Sleepiness Scale (ESS): Rates chance of dozing in 8 situations (0-3 each, total 0-24). Score ≥10 suggests excessive daytime sleepiness. [1][3]
Insomnia Severity Index (ISI): Total score: 0-7 normal; 8-14 mild; 15-21 moderate; 22-28 severe. [1]
4. Insomnia Disorder
High Yield — DSM-5 Insomnia Disorder Criteria
"A predominant complaint of dissatisfaction with sleep quantity or quality in addition to DIS (difficulty initiating sleep), DMS (difficulty maintaining sleep), and EMA (early morning awakening). 3 nights per week. At least 3 months. Distress and impairment in functioning. Exclusion criteria." [1]
Breaking this down:
- Subjective complaint — the patient is dissatisfied (this is key; PSG is not required for diagnosis)
- At least one of: Difficulty initiating sleep (DIS), difficulty maintaining sleep (DMS), or early morning awakening (EMA) with inability to return to sleep
- Frequency: ≥3 nights per week
- Duration: ≥3 months (this distinguishes chronic insomnia from acute insomnia)
- Functional impairment or significant distress
- Not better explained by another sleep disorder, substance, or inadequate sleep opportunity
"DSM-IV prevalence HK 22.1%, US 22.1%. DSM-5 prevalence 10.8%." [1]
The stricter DSM-5 criteria (requiring 3 months + 3 nights/week) reduce prevalence from ~22% to ~11%.
"By diagnosis – primary, comorbid, or due to other diagnoses. By duration — acute ( < 1 mth), subacute (1-3 mth) or chronic ( > 3 mth). 3P model — predisposing, precipitating, and perpetuating factors." [1]
High Yield — 3P (Spielman) Model of Insomnia
"According to the 3P model, insomnia becomes chronic due to perpetuating factors." [1]
- Predisposing factors: Genetic vulnerability, anxious temperament, female sex, older age, hyperarousal tendency
- Precipitating factors: Life stress, medical illness, bereavement, job loss — triggers acute insomnia
- Perpetuating factors: Maladaptive sleep behaviours (spending too long in bed, napping, clock-watching, irregular schedule), catastrophic cognitions about sleep, conditioned arousal in bed
The model explains why acute insomnia (triggered by a stressor) becomes chronic insomnia — even after the precipitant resolves, the perpetuating factors maintain the problem. This is the rationale for CBT-I targeting perpetuating factors.
"It is difficult to determine whether insomnia is directly caused by the comorbid condition, so the term 'secondary insomnia' should be avoided. For most situations, symptomatic treatment of insomnia is necessary." [1]
This is a key exam point: modern practice uses "comorbid insomnia" rather than "secondary insomnia" because of the bidirectional relationship between insomnia and other conditions (e.g., insomnia worsens depression, depression worsens insomnia). Both should be treated simultaneously.
"Medical disorders, e.g. pain, night sweating, hot flushes, cancer, COAD, parkinsonism. Psychiatric disorders, e.g. major depression, anxiety disorders, substance use, schizophrenia. Sleep disorders, e.g. circadian sleep-wake disorder, obstructive sleep apnea, periodic limb movement disorder." [1]
Exam Trap
Don't automatically assume insomnia in a depressed patient is "just depression." Both insomnia and depression need active treatment. Similarly, a patient with insomnia may have undiagnosed OSA or RLS causing the sleep disturbance — always screen for these.
"The primary treatment goals are: (1) to improve sleep quality and quantity; (2) to improve insomnia related daytime impairments." [1]
High Yield — Treatment of Insomnia: Drug Classes
Prescribed and Approved drugs:
- BZ receptor agonists, e.g. Zopiclone, Zolpidem
- Melatonin receptor agonist, e.g. Ramelteon
- Low dose Doxepin
Off-label drugs:
- Sedative antidepressants, e.g. Remeron (mirtazapine), Trazodone, Paroxetine
- Sedative antipsychotics, e.g. Quetiapine
Drugs with health risks:
- Benzodiazepines, e.g. Lorazepam, Clonazepam
Over-the-counter drugs:
- Promethazine, Melatonin, Valerian [1]
Z-drugs: Zolpidem and Zopiclone
Mechanism: Both are non-benzodiazepine hypnotics ("Z-drugs") that bind to the BZ1 receptor subtype (α1/α5 subunits) of the GABA-A receptor complex. This selective binding explains why they have hypnotic effects without significant myorelaxant and anticonvulsant effects (these are mediated by other BZ receptor subtypes). [1]
By contrast, benzodiazepines non-selectively bind to and activate ALL BZ receptor subtypes — hence their broader profile of sedation + anxiolysis + myorelaxation + anticonvulsant effect + greater abuse potential. [1]
Side effects: Hangover, Daytime sleepiness, Falls, Motor incoordination, Amnesia, Poor memory, Automatism, Sleepwalking. Tolerance, abuse and dependence. [1]
"FDA recent guideline suggested Zolpidem 5mg or Zopiclone 3.75mg for women to avoid daytime sedation and impairment in activities that require alertness." [1]
Why lower dose for women? Women metabolize zolpidem more slowly (lower CYP activity, lower body weight, higher body fat → larger volume of distribution) → higher morning blood levels → impaired driving.
"FDA warning on sleep related complex behavior (sleepwalking, sleep driving)." [1]
| Property | Zolpidem | Zopiclone |
|---|---|---|
| Metabolism | CYP3A4 (60%), CYP2C9 (20%), CYP1A2 (15%) | CYP3A4 (major), CYP2C8 |
| Metabolites | Inactive | One active metabolite (11%) |
| Excretion | 48-67% urine, rest in bile; < 1% active drug in urine | Active metabolite in urine |
| Tmax | 1.6 hrs | Longer than zolpidem |
| T½ | 2.5 hrs | Longer than zolpidem (~5-6h) |
| Drug interactions | CYP3A4 inhibitors (erythromycin → ↑levels) and inducers (phenytoin, St. John's wort → ↓levels) | Same CYP3A4 interactions |
Exam Point
Zolpidem has a shorter half-life (2.5h) → better for sleep-onset insomnia. Zopiclone has a longer half-life → better for sleep maintenance insomnia but more hangover effect. Both carry risks of dependence, complex sleep behaviours, and falls (especially in elderly).
| Component | What It Involves | Why It Works |
|---|---|---|
| Sleep education | Explain sleep physiology, two-process model, sleep hygiene | Corrects misconceptions; empowers patient |
| Stimulus control | Bed only for sleep/sex; leave bed if awake > 15-20 min; fixed wake time | Breaks conditioned arousal association with bed |
| Sleep restriction | Limit time in bed to actual sleep time (e.g., if sleeping 5h, allow only 5h in bed) → gradually increase | Creates mild sleep deprivation → increases homeostatic drive → consolidates sleep |
| Relaxation training | Progressive muscle relaxation, diaphragmatic breathing, guided imagery | Reduces somatic and cognitive hyperarousal |
| Cognitive therapy | Challenge catastrophic thoughts about sleep ("I'll never function if I don't sleep 8 hours") | Reduces cognitive arousal and performance anxiety |
CBT-I is the first-line treatment for chronic insomnia in all major guidelines. It has durable effects (unlike medications, which work only while being taken) and no side effects.
"Stepped care model (provides least restrictive and costly treatment first) for some common medical conditions, e.g. insomnia." [1]
- Mild: Sleep hygiene education, self-help CBT-I
- Moderate: Therapist-delivered CBT-I, short-term pharmacotherapy
- Severe: Specialist referral, combination therapy, address comorbidities
5. Hypersomnolence Disorder
"Sleepiness is a normal physiological drive… Differs from feelings of tiredness, fatigue and lack of energy." [1]
This is a critical clinical distinction. Sleepiness = tendency to fall asleep (patient dozes off during activities). Fatigue = lack of energy, weariness (patient feels exhausted but may not actually fall asleep). Sleepiness points to sleep disorders; fatigue has a broader differential (depression, anaemia, hypothyroidism, chronic fatigue syndrome, etc.). [1][3]
"Insufficient sleep, Obstructive sleep apnea syndrome, Narcolepsy, Idiopathic hypersomnolence, Periodic limb movement disorder, Sleep-wake circadian disorder, Medical, psychiatric and substance-use disorders." [1]
The commonest cause is simply insufficient sleep (voluntary sleep restriction in modern society). Always rule this out first.
"An objective measure of sleepiness by asking the patient to try to sleep for 20 min at 2-hour interval starting 2-4 hours after awakening for 4-5 times. Pathological sleepiness: mean sleep latency < 5 min. REM latency – for diagnosis of narcolepsy (presence of at least one sleep onset REM on four naps)." [1]
More precisely, narcolepsy diagnosis on MSLT requires: mean sleep latency ≤ 8 min AND ≥ 2 sleep-onset REM periods (SOREMPs) on 4-5 naps (or 1 SOREMP on MSLT + 1 SOREMP on preceding nocturnal PSG). [1]
High Yield — Narcolepsy: Classic Tetrad
Four characteristic symptoms:
- Excessive sleepiness or sleep attacks
- Cataplexy — sudden loss of bilateral muscle tone provoked by strong emotion. Consciousness remains clear, varies in severity, head drop, facial sagging, jaw drop, slurred speech, buckling of knees, few seconds to minutes
- Sleep paralysis — transient, generalized inability to move or to speak during transition between REM sleep and wakefulness, lasts 1 to several minutes
- Hypnagogic hallucination — vivid perceptual experiences occurring at sleep onset, visual, tactile, kinetic, affect is often fear or dread [1]
Why does narcolepsy produce these symptoms? Narcolepsy Type 1 is caused by loss of orexin (hypocretin)-producing neurons in the lateral hypothalamus (autoimmune destruction, associated with HLA DQB1*0602). Orexin normally stabilises the switch between wake and sleep states. Without it, the brain intrudes into REM inappropriately:
- Sleep attacks = sudden intrusion of sleep into wakefulness
- Cataplexy = REM atonia intruding into wakefulness (triggered by emotion because the amygdala activates the REM-atonia pathway)
- Sleep paralysis = persistence of REM atonia into wakefulness on awakening
- Hypnagogic hallucinations = REM dreaming intruding into the wake-sleep transition
"Type 1 (orexin/hypocretin-1 deficiency and cataplexy). Type 2 (normal orexin/hypocretin level and no cataplexy)." [1]
| Feature | Narcolepsy Type 1 | Narcolepsy Type 2 |
|---|---|---|
| Cataplexy | Present | Absent |
| CSF hypocretin-1 | Low ( ≤ 110 pg/mL) | Normal |
| HLA DQB1*0602 | Often positive | Variable |
| Pathophysiology | Orexin neuron loss | Unknown |
Diagnosis:
"Diagnosed by overnight polysomnography and MSLT (Short sleep latency < 5 minutes and Sleep onset REM < 20 minutes). HLA DQB10602 allele. CSF hypocretin-1 level."* [1]
Treatment:
"Stimulant drugs (Modafinil, armodafinil, methylphenidate) to suppress daytime sleepiness; Antidepressants for cataplexy; Gamma hydroxybutyrate for both symptoms." [1]
Why antidepressants for cataplexy? SSRIs/SNRIs/TCAs suppress REM sleep → reduce cataplexy, sleep paralysis, and hypnagogic hallucinations (all REM-related phenomena).
"Motor vehicle accidents, Work-related accidents, Impaired neuropsychological function, Impaired motor performance, Reduced quality of life." [1]
This has medicolegal implications — patients with untreated severe sleepiness may need to be advised about driving restrictions.
6.1 Obstructive Sleep Apnoea Syndrome (OSAS)
High Yield — OSAS Symptoms, Diagnosis, Treatment
Symptoms: Loud and habitual snoring, Intermittent pattern of snoring, Choking/waking up with SOB, Insomnia, Excessive sleep movement, Daytime sleepiness, Dry mouth, Nocturia, Morning headache, Poor concentration and memory. [1]
Diagnosed by overnight polysomnography. AHI: 5-15 = mild, 15-30 = moderate, > 30 = severe. [1]
Treatment: CPAP, dental appliance, surgery and positional device (for supine isolated OSA). [1]
Definitions (from supporting notes [3]):
- Apnoea: Complete cessation of oronasal airflow ≥ 10 seconds
- Hypopnoea: ≥ 30% reduction in oronasal flow for ≥ 10 seconds + ≥ 3% oxygen desaturation or EEG arousal
- AHI (Apnoea-Hypopnoea Index): Number of apnoeas + hypopnoeas per hour of sleep
Risk factors: Male sex (or postmenopausal women), obesity, craniofacial abnormalities (micrognathia, macroglossia, adenotonsillar hypertrophy), endocrine diseases (acromegaly, hypothyroidism), alcohol, smoking, Down's syndrome. [3]
Pathophysiology: During sleep, pharyngeal muscle tone decreases. In OSA, the upper airway collapses (anatomical narrowing + reduced tone) → airflow obstruction → hypoxia + hypercapnia → arousal → airway reopens → patient falls back asleep → cycle repeats → fragmented sleep + intermittent hypoxia.
Why nocturia in OSA? Intrathoracic pressure swings → increased atrial natriuretic peptide (ANP) release → natriuresis.
Why morning headache? CO2 retention during apnoeas → cerebral vasodilation → headache.
Complications: Hypertension (OSA is a recognised secondary cause of HTN), cardiovascular disease, arrhythmias, stroke, metabolic syndrome, accidents. [3]
7. Parasomnias
"Any abnormal behavior occurring during sleep. Classify according to the sleep phase parasomnia occurs." [1]
High Yield — NREM vs REM Parasomnia Differentiation
| Feature | NREM Parasomnia | REM Parasomnia |
|---|---|---|
| Timing | First half of the night | Later half of the night |
| Recall | Unable to recall behavior | Partial recall of behavior or dream content |
| Dream relation | Unrelated to dreams | Acting out of dream content |
| Examples | Sleepwalking, sleep terrors, sleep-related eating disorder | RBD, sleep paralysis, nightmares |
7.1 NREM Parasomnias
"Incomplete transition from deep sleep to wake. Talking, hand movement, standing and walking, urinating, eating. Neurodevelopmental disorder: peak age of onset 7 yrs old. Precipitating factors: physical exertion, heavy exercise, fever, drugs, OSAS, PLMD." [1]
"Treatment: Accident prevention, Treat the precipitating factors (e.g., OSAS), Drug treatment: clonazepam." [1]
Why does sleepwalking peak in childhood? Children have the most SWS (NREM 3/4) → more opportunities for incomplete arousal from deep sleep. It usually resolves with maturation.
"Eating food with resultant increased weight. Treatment: SSRIs, topiramate, clonazepam." [1]
The lecture provides a useful comparison table of sleepwalking vs. SRED [1]:
| Feature | Sleepwalking | SRED |
|---|---|---|
| Age at onset | Childhood | Middle age |
| Trigger factor | Uncommon (19%) | Common (62%) |
| Nightly episodes | Uncommon (10%) | Common (73%) |
| Total loss of awareness | Common (39%) | Rare (7%) |
| Dream-like mentation | Common (67%) | Rare (0%) |
| Injuries | Common (52%) | Rare (7%) |
| History of eating disorder | Uncommon (14%) | Common (60%) |
| Current insomnia | Rare (5%) | Common (73%) |
| Psychiatric disorders | Uncommon (21%) | Common (62%) |
7.2 REM Parasomnias
High Yield — RBD and Neurodegeneration Risk
"Clinical features: Frequent vivid, action-packed, violent dream; loss of muscle atonia that results in enactment of dream content. 50% of cases are associated with neurological conditions: organic lesions at brain stem area, other neurodegenerative disorders which affect REM sleep control. High future risk of neurodegenerative disorders. OSA can precipitate RBD. Treatment: Clonazepam." [1]
Why is RBD so important? In normal REM sleep, the brainstem actively inhibits motor neurons (muscle atonia) so you don't act out your dreams. In RBD, this atonia mechanism fails. The patient punches, kicks, or leaps out of bed during vivid dreams — often injuring themselves or bed partners.
The neurodegenerative link is critical: Idiopathic RBD is a strong prodromal marker of α-synucleinopathies (Parkinson's disease, dementia with Lewy bodies, multiple system atrophy). Up to 80-90% of patients with idiopathic RBD will develop a neurodegenerative disease within 10-15 years. This makes RBD a window for early intervention research. [1]
"Awakening from REM with muscle atonia → 'ghost oppression'. Clear sensorium, difficulty in breathing, acute anxiety, hypnagogic imagery. Mostly isolated. Precipitating factor: sleep deprivation, irregular sleep habits, overtiredness, stress. More frequent sleep paralysis is either familial or associated with narcolepsy. Tx: TCAs and SSRIs which suppress REM sleep." [1]
Why "ghost oppression"? In Chinese culture (鬼壓床), the experience of paralysis with fear and visual hallucinations during the transition from sleep to wake is culturally interpreted as a supernatural attack. Understanding the REM-based mechanism allows reassurance.
"Mental activity during sleep. Most dreams occur in REM sleep. Function – organization of memory." [1]
"Drugs that increase dreaming include: beta-blockers (atenolol, propranolol), antidepressants (SSRIs, SNRIs), antipsychotics (Risperidone), GABA agonists (gabapentin, zopiclone, BZs), anticholinesterase inhibitors (donepezil, rivastigmine), and dopamine agonists (L-dopa)." [1]
Treatment of nightmares:
"Recommended treatment of PTSD-associated nightmares and nightmare disorder — image rehearsal therapy. Treatment of PTSD-associated nightmare (second line): atypical antipsychotics, clonidine, gabapentin, prazosin. Treatment of nightmare disorder (second line): prazosin, nitrazepam, triazolam." [1]
Prazosin (alpha-1 adrenergic blocker) is a classic exam answer for PTSD-related nightmares. It reduces noradrenergic activation during sleep, decreasing nightmare frequency and intensity.
8.1 Restless Leg Syndrome (RLS) / Periodic Limb Movement Disorder (PLMD)
High Yield — RLS/PLMD
"An urge to move one's legs which is often accompanied by an unpleasant sensation. 80-90% will have PLMD which is a common cause of insomnia and excessive daytime sleepiness first diagnosed during sleep study — characterized by periodic episodes of repetitive and highly stereotyped limb movements during sleep, causes repeated arousal. Sequence of 4 or more LMs separated by at least 5 sec and not more than 90 sec." [1]
"2 phenotypes of RLS — 1. early-onset, familial or idiopathic RLS (more common); 2. late-onset, sporadic or secondary RLS — iron deficiency anemia, renal failure, neuropathy." [1]
"RLS worsens during rest and at night." [1]
"Ferritin level — iron supplement indicated when ferritin < 75 µg/L (Fe sulphate 325mg bd on an empty stomach)." [1]
"RLS diagnosis based on history. PLMD diagnosed by overnight polysomnography." [1]
"Treatment — alpha-2-delta ligands (gabapentin, pregabalin), dopamine agonists (L-dopa, pramipexole, ropinirole), opioids (oxycodone), clonazepam." [1]
RLS diagnostic criteria (IRLSSG): The urge to move the legs must:
- Begin or worsen during periods of rest/inactivity
- Be partially or totally relieved by movement
- Occur exclusively or predominantly in the evening/night
- Not be solely accounted for by another medical/behavioural condition
Why check ferritin < 75 µg/L (not the usual anaemia threshold of < 15)? Brain iron stores correlate with ferritin levels but the brain needs a higher threshold for dopamine synthesis. Low brain iron → reduced tyrosine hydroxylase activity → reduced dopamine → RLS. Iron supplementation is the simplest first intervention.
Alpha-2-delta ligands (gabapentin, pregabalin) are now preferred first-line over dopamine agonists because of the risk of augmentation (paradoxical worsening of RLS with long-term dopamine agonist use — symptoms become more severe, occur earlier in the day, and spread to the arms). [1]
High Yield — CRSWD: Delayed Sleep-Wake Phase Disorder
"The most common type of CRSWD is delayed SWPD (DSWPD) — 80% of all CRSWD cases, followed by advanced SWPD, non-24 hr SWPD, and irregular SWPD. DSWPD is more common in adolescents and young adults." [1]
"Sleep diary, actigraphy, chronotype questionnaire, salivary dim light melatonin onset (DLMO)." [1]
"Low dose melatonin (0.5 mg) 5 hr before habitual sleep onset or 2-4 hr before DLMO. Evening light restriction and 2 hr of bright light therapy (10000 lux) on awakening." [1]
| Type | Who Gets It | Sleep Pattern | Treatment |
|---|---|---|---|
| Delayed SWPD | Adolescents, young adults | Sleep onset very late (e.g. 3-4 am), wake late (e.g. 11 am-noon); normal quality when allowed to sleep at preferred time | Low-dose melatonin before DLMO; morning bright light; evening light restriction |
| Advanced SWPD | Elderly | Sleep onset very early (e.g. 7-8 pm), wake very early (e.g. 3-4 am) | Evening bright light; morning light restriction |
| Non-24h SWPD | Blind individuals | Free-running clock (sleep onset drifts later each day) | Melatonin, tasimelteon |
| Irregular SWPD | Dementia, brain injury | No consolidated sleep period; sleep scattered across 24h | Structured zeitgebers, melatonin, bright light |
9.1 General Approaches for Reversing Sleepiness
"Regular and adequate sleep. Caffeine (200 mg or 2-3 cups) not later than 4 pm. Short naps (15 min). Bright light therapy (10000 lux for 30 min) for shift work, jet lag, seasonal affective disorder. Nature of shift work (forward shift is better — easier to delay sleep, regular night shift, 12-hour 2-shift). Nasal CPAP, surgery, and dental appliance (OSAS). Modafinil and CNS stimulants (narcolepsy)." [1]
Why forward shift rotation? It is easier to delay your circadian clock (stay up later) than to advance it (go to bed earlier). Rotating shifts in a clockwise direction (morning → evening → night) is less disruptive than anti-clockwise.
10. Exam Intelligence
| Trap | Why It's Wrong | Correct Answer |
|---|---|---|
| Calling all insomnia "secondary" when a comorbid condition exists | Bidirectional relationship; "secondary" implies causality that is usually unproven | Use "comorbid insomnia"; treat both conditions |
| Diagnosing narcolepsy without cataplexy as Type 1 | Type 1 requires cataplexy OR low CSF hypocretin-1 | Without cataplexy and with normal hypocretin → Type 2 |
| Using PSG to diagnose insomnia | Insomnia is a clinical/subjective diagnosis | PSG is for OSA, narcolepsy, PLMD, RBD — not routine insomnia |
| Recommending benzodiazepines first-line for chronic insomnia | BZs have health risks (tolerance, dependence, falls, rebound) | CBT-I is first-line; Z-drugs if pharmacotherapy needed |
| Sleepwalking occurring in second half of night | NREM parasomnias (sleepwalking) = first half (deep sleep predominates) | Second half = REM parasomnias (RBD, nightmares) |
| Using ferritin < 15 µg/L as threshold for iron supplementation in RLS | Brain iron threshold is higher | Ferritin < 75 µg/L triggers iron supplementation for RLS |
| Confusing sleepiness with fatigue | Sleepiness = tendency to doze; fatigue = lack of energy | Different differential diagnoses and management |
| Missing RBD as prodromal marker of neurodegeneration | Thinking it's benign | Up to 80-90% develop α-synucleinopathy |
Depression classically shows: shortened REM latency (< 90 min), increased REM density, decreased SWS. This is contrasted with the 2023 MCQ Q75, which asked the most suggestive symptom of depression over GAD — the answer was weight gain (D), since difficulty falling asleep, loss of concentration, and muscle tension overlap significantly with GAD. [5]
11. Past Paper Questions
Stem: "Mr. Chan is a 40-year-old gentleman who complained of loud snoring and daytime sleepiness for six months. His wife observed that he would stop breathing for more than ten seconds when he was fast asleep."
- (a) What is the most likely diagnosis? (2 marks) → Obstructive sleep apnoea syndrome (OSAS)
- (b) How do you confirm the diagnosis? (2 marks) → Overnight polysomnography (PSG) / sleep study
- (c) What is the measurement for the severity of the disease? (2 marks) → Apnoea-Hypopnoea Index (AHI) — Mild 5-15, Moderate 15-30, Severe > 30
- (d) What is the investigation to locate the cause of the disease? (2 marks) → Head and neck examination / nasendoscopy / lateral cephalometry / CT or MRI of upper airway — to identify site of obstruction (e.g., tonsillar hypertrophy, retrognathia)
- (e) Name two treatments. (2 marks) → CPAP (continuous positive airway pressure) and dental/mandibular advancement appliance (also accept weight loss, surgery, positional device)
Stem: "Difficulty staying asleep, and in particular, waking too early and unable to get back to sleep." Answer: E. Major depressive disorder Rationale: Early morning awakening (EMA) is a hallmark biological symptom of depression. While insomnia disorder also includes EMA, the EMQ is asking for the psychiatric diagnosis most associated with this specific pattern. In depression, EMA reflects circadian rhythm disturbance (shortened REM latency, phase-advanced cortisol secretion).
Stem: "A 45-year-old woman presents with low mood and fatigue for 6 months. Difficulty falling asleep because worried about her health. Muscle tension, weight gain 5 kg, loss of concentration. Denies suicidal ideation. Which symptom MOST SUGGESTIVE of depression over generalised anxiety disorder?" Answer: D. Weight gain Rationale: DIS due to worry, muscle tension, and loss of concentration are all common in GAD. Weight change (gain or loss) is more characteristic of depression (change in appetite is a core DSM-5 criterion for major depressive episode). This is a discriminator question — you must identify which symptom has higher specificity for depression vs. GAD.
Stem: "Mr. Lee, a 45-year-old patient, complains of 'tiredness'."
- (a) Name four differential diagnoses for fatigue. → Depression, hypothyroidism, anaemia, diabetes mellitus (also accept OSA, malignancy, chronic kidney disease, heart failure)
- (b) Name four symptoms to help confirm/exclude your differentials. → Low mood/anhedonia (depression), cold intolerance/weight gain (hypothyroid), pallor/dyspnoea on exertion (anaemia), polyuria/polydipsia (DM)
- (c) Suggest two questions to screen for depression. → PHQ-2: "Over the past 2 weeks, have you been feeling down, depressed or hopeless?" and "Over the past 2 weeks, have you had little interest or pleasure in doing things?"
Note on Fatigue vs Sleepiness
This SAQ tests the distinction emphasised in the lecture: "tiredness" needs to be differentiated from sleepiness. The lecture explicitly states that sleepiness differs from feelings of tiredness, fatigue and lack of energy. [1] If the patient is actually falling asleep during the day, the differential shifts to OSA, narcolepsy, PLMD, and circadian disorders.
- CFB PSY02 classifies sleep-wake disorders within DSM-5 under: Insomnia disorder, Hypersomnolence/Narcolepsy, Breathing-related, Circadian rhythm, Parasomnias, RLS/PLMD, Substance/medication-induced. [4]
- GC 024 (A Fatigued and Sleepy Patient) overlaps with this lecture in differential diagnosis of sleepiness and approach to the sleepy patient. Ensure you can differentiate sleepiness from fatigue.
- GC 081 (Seizure and LOC) is relevant because EEG is used in both epilepsy and sleep medicine (sleep staging requires EEG), and nocturnal seizures must be differentiated from parasomnias.
- OSA as a secondary cause of hypertension is a common exam point across multiple lectures. [9]
- AOS Psychiatry notes that sleeping pills and BZDs will not be used in long-term management — examiners may test this. [10]
High Yield Summary
Sleep physiology: Two-process model (Process C = circadian/melatonin/SCN; Process S = homeostatic/adenosine). Sleep architecture cycles every 90 min (NREM 1→2→3/4→REM). More SWS in first half, more REM in second half. REM latency ~90 min; shortened in depression.
Insomnia Disorder (DSM-5): DIS/DMS/EMA + ≥3 nights/week + ≥3 months + distress/impairment. 3P model explains chronification. Treatment: CBT-I first-line; Z-drugs (zolpidem/zopiclone bind BZ1 selectively); avoid long-term BZs.
Narcolepsy: Tetrad = sleepiness + cataplexy + sleep paralysis + hypnagogic hallucinations. Type 1 = low hypocretin + cataplexy. Dx by PSG + MSLT (mean latency ≤8 min, ≥2 SOREMPs). Tx: stimulants (modafinil) for sleepiness; antidepressants for cataplexy.
OSAS: AHI grading (5-15 mild, 15-30 moderate, >30 severe). Dx by PSG. Tx: CPAP, dental appliance, surgery, positional device.
Parasomnias: NREM (first half, no recall) vs REM (second half, dream enactment). RBD → high risk of α-synucleinopathy. Tx: clonazepam.
RLS/PLMD: Urge to move legs, worse at rest/night. Check ferritin (supplement if <75). Tx: alpha-2-delta ligands > dopamine agonists.
CRSWD: DSWPD most common (adolescents). Tx: low-dose melatonin + morning bright light + evening light restriction.
Active Recall - Lecture Notes
[1] Lecture slides: GC 165. I can't fall asleep Sleep physiology and Sleep disorders.pdf [2] Senior notes: Ryan Ho Psychiatry.pdf (Section 9.2 Sleep Disorders) [3] Senior notes: Maksim Medicine Notes.pdf (Section 12.9 Sleep-related breathing disorders); Ryan Ho Respiratory.pdf (Section 3.8) [4] Lecture slides: CFB (PSY02) Classification and Diagnosis of Psychiatric Illness.pdf (Sleep-wake disorders slide) [5] Past papers: 2023 Fourth Summative MCQ.pdf (Q75) [6] Past papers: 2017 Fourth Summative SAQ.pdf (Q2) [7] Past papers: 2020 Fourth Summative Assessment MCQ paper.pdf (EMQ Section VI Q24) [8] Past papers: 2018 Fourth Summative SAQ.pdf (Q10) [9] Senior notes: Block A - High blood pressure_ hypertension.pdf [10] AOS material: AOS - Psych.md
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