Circadian Rhythms and Psychiatry

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Core Concepts - Body's Master Clock

  • Endogenous, self-sustaining ~24-hour cycles regulating sleep-wake, hormones, metabolism.
  • Suprachiasmatic Nucleus (SCN): Master pacemaker in anterior hypothalamus.
    • Receives direct light input from intrinsically photosensitive retinal ganglion cells (ipRGCs) via retinohypothalamic tract (RHT).
    • Synchronizes peripheral "slave" oscillators in other tissues.
  • Key Hormones:
    • Melatonin: Secreted by pineal gland in darkness; promotes sleep. Light suppresses its release.
    • Cortisol: Adrenal hormone; peaks in early morning, promoting alertness.
  • Clock Genes: PER, CRY, CLOCK, BMAL1 form core transcriptional-translational feedback loops (TTFLs) driving cellular rhythms. Suprachiasmatic Nucleus Light Input Pathway

⭐ The SCN primarily uses GABA as its neurotransmitter for both internal communication and output signaling to other brain regions.

Regulation & Measurement - Keeping in Sync

  • Regulation (Entrainment):
    • SCN (hypothalamus): Master biological clock.
    • Entrained by Zeitgebers (external cues).
    • Light: Most potent zeitgeber.
      • Pathway: Light → ipRGCs (retina, melanopsin) → Retinohypothalamic Tract (RHT) → SCN.
    • Other zeitgebers: Social cues, meal timing, physical activity, temperature.
  • Measurement:
    • Actigraphy: Wrist-worn device; measures motor activity to estimate sleep-wake cycles.
    • Dim Light Melatonin Onset (DLMO): Gold standard for assessing circadian phase.
      • Serial saliva/plasma melatonin sampling under dim light (<10 lux).

      ⭐ DLMO typically occurs 2-3 hours prior to habitual sleep onset, marking the opening of the "sleep gate".

    • Core Body Temperature (CBT): Rhythm with nadir during late sleep/early morning.
    • Sleep Diaries: Subjective patient logs. Retinohypothalamic pathway and SCN light entrainment
  • Depression: Often phase-delayed (later sleep/wake). Altered melatonin & cortisol rhythms.
    • Sleep disturbances: Insomnia, hypersomnia.
  • Bipolar Disorder: Extreme sensitivity to rhythm changes.
    • Mania: ↓ sleep needs, often phase-advanced.
    • Depression: Hypersomnia, phase-delayed.

    ⭐ Sleep deprivation can trigger manic episodes in bipolar disorder.

  • Schizophrenia: Significant disruption of sleep-wake cycles & activity.
    • Clock gene associations (e.g., PER3, CLOCK).
  • Anxiety Disorders: High rates of sleep disturbances.
    • Potential HPA axis & circadian interaction.
  • ADHD: Common delayed sleep-wake phase disorder (DSWPD).
    • Melatonin often used for sleep onset.
  • Therapeutic Target: Chronotherapies (light therapy, melatonin) show promise. Circadian Rhythm Disruption and Psychiatric Disordersoka

Chronotherapeutics - Timing for Wellness

  • Light Therapy (Bright Light Therapy - BLT):
    • Exposure: 10,000 lux light, typically 30 min/day (morning).
    • Indications: SAD (Seasonal Affective Disorder), non-seasonal depression, sleep phase disorders.
    • Mechanism: Resets Suprachiasmatic Nucleus (SCN), ↓ melatonin.
  • Melatonin:
    • Regulates sleep-wake; Dose: 0.5-5 mg at bedtime (hs).
    • Indications: Insomnia, jet lag, Delayed Sleep-Wake Phase Disorder (DSWPD).
    • Ramelteon: Selective MT1/MT2 receptor agonist.
  • Agomelatine:
    • MT1/MT2 agonist & 5-HT2C antagonist.
    • Antidepressant; resynchronizes circadian rhythms.
    • Dose: 25-50 mg daily; ⚠️ Monitor Liver Function Tests (LFTs).
  • Behavioral Strategies:
    • Sleep hygiene education, scheduled sleep-wake times.
    • Timed exercise, meal intake.
    • Social Rhythm Therapy (SRT) for bipolar disorder.

⭐ Light therapy (10,000 lux) is a first-line treatment for Seasonal Affective Disorder (SAD).

High-Yield Points - ⚡ Biggest Takeaways

  • SCN (Suprachiasmatic Nucleus) in hypothalamus: the master circadian clock.
  • Melatonin (pineal gland) regulates sleep; light exposure suppresses its release.
  • Circadian disruptions are prominent in mood disorders (e.g., depression, bipolar disorder).
  • DSWPD: Delayed sleep onset/offset ("night owls").
  • ASWPD: Advanced sleep onset/offset ("morning larks").
  • Light therapy: key treatment for SAD and certain circadian rhythm sleep disorders.
  • Clock genes (e.g., PER, CRY, BMAL1) underpin circadian rhythmicity.

Practice Questions: Circadian Rhythms and Psychiatry

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Which condition is associated with periodic discharges on EEG at 4-second intervals?

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Flashcards: Circadian Rhythms and Psychiatry

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Which hormone levels are increased in mania?_____

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Which hormone levels are increased in mania?_____

Dopamine and NE

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