Biopsychology
Circadian Rhythm
The 24-hour internal clock that runs sleep, hormones, and cognition
The circadian rhythm is an endogenous, roughly 24-hour cycle generated by the suprachiasmatic nucleus (SCN) in the hypothalamus. It coordinates sleep-wake timing, hormone release (melatonin, cortisol), body temperature, and cognitive performance. Discovered behaviorally by de Mairan in 1729 and molecularly by Konopka and Benzer in 1971 — work that earned Hall, Rosbash, and Young the 2017 Nobel Prize — the rhythm is set by an autoregulatory transcription-translation feedback loop and synchronized to the external day primarily by light hitting intrinsically photosensitive retinal ganglion cells.
- Master clockSuprachiasmatic nucleus (SCN), hypothalamus
- Period~24.2 hours in humans (free-running)
- Primary zeitgeberLight, via melanopsin-containing retinal ganglion cells
- Molecular corePER, CRY, CLOCK, BMAL1 transcription-translation loop
- Nobel PrizeHall, Rosbash, Young (2017) for clock genes
- DiscoveredBehaviorally by de Mairan, 1729 (mimosa plant)
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Why circadian rhythm matters
- Sleep medicine. Insomnia and delayed sleep phase syndrome are circadian disorders.
- Shift work. Disruption raises risks of metabolic disease, cancer, and accidents.
- School timing. Adolescent biology favors later start times for learning and well-being.
- Pharmacology. Drug efficacy and toxicity vary across the day (chronotherapy).
- Athletic performance. Strength and reaction time peak in late afternoon.
- Mental health. Depression, bipolar disorder, and seasonal affective disorder involve clock disruption.
- Aging. Clock amplitude decreases with age, contributing to sleep fragmentation.
Common misconceptions
- It's exactly 24 hours. Average free-running period in humans is closer to 24.2.
- Melatonin makes you sleep. It signals night; it does not directly induce sleep.
- Owls are lazy. Chronotype has strong biological and genetic components.
- The rhythm is just sleep. Hormones, temperature, immunity, and cognition all cycle.
- Light at any wavelength resets the clock. Blue wavelengths near 480 nm dominate.
- You can fully adapt to any schedule. Permanent shift workers rarely re-entrain completely.
Frequently asked questions
Where is the master clock?
The suprachiasmatic nucleus, two clusters of about 20,000 neurons in the anterior hypothalamus directly above the optic chiasm. Lesion studies in rodents and humans show that destroying the SCN abolishes circadian rhythms in sleep, hormones, and behavior. The SCN drives peripheral clocks throughout the body — liver, muscle, fat, immune system — through neural and hormonal signals, with the SCN as conductor and tissues as orchestra.
What is the molecular clock?
Per Hall, Rosbash, and Young's work, four core proteins drive the cycle. CLOCK and BMAL1 form a heterodimer that activates transcription of PER and CRY genes. PER and CRY proteins accumulate, dimerize, enter the nucleus, and inhibit CLOCK/BMAL1 — shutting off their own production. Degradation of PER/CRY then releases the inhibition, restarting the cycle. The whole loop takes about 24 hours and explains why mutations in any of these genes shift sleep timing.
How does light entrain the clock?
Light hits intrinsically photosensitive retinal ganglion cells (ipRGCs) containing the photopigment melanopsin, discovered by Berson, Hattar, and others in 2002. These cells project to the SCN via the retinohypothalamic tract. Morning light advances the clock (earlier sleep onset); evening light delays it. Blue wavelengths near 480 nm are most effective, which is why screens at night can shift sleep timing by 30-90 minutes.
What is melatonin's role?
Melatonin is secreted by the pineal gland under SCN control, rising in the evening (dim-light melatonin onset, DLMO, around 9 pm in adults), peaking in the middle of the night, and falling before waking. It signals "biological night" to the rest of the body but is not the cause of sleep itself — sleep can occur without melatonin, and melatonin can be high without sleep. Exogenous melatonin (0.3-0.5 mg) shifts the clock; higher doses act more like a hypnotic.
Why does jet lag happen?
Travel across time zones desynchronizes the SCN from the new local light cycle, and peripheral clocks lag the SCN. Eastward travel is harder because it requires phase advance, while the human free-running period is slightly longer than 24 hours, making delays easier. Recovery typically takes about one day per time zone crossed. Strategic light exposure, melatonin timing, and meal timing can speed adaptation.
What is chronotype?
Individual differences in preferred sleep timing, ranging from morning types ("larks") to evening types ("owls"). Chronotype is partly genetic — variants in PER3, CLOCK, and other clock genes — and shifts across the lifespan, with adolescents biologically delayed (Carskadon, 2002) and older adults advancing. Forcing students to start school early conflicts with adolescent chronotype; later start times have been linked to improved attendance, sleep, and academic performance.
What happens when the rhythm is disrupted?
Chronic disruption — shift work, frequent travel, irregular sleep — is associated with elevated risk of metabolic syndrome, cardiovascular disease, certain cancers (the IARC classified shift work as probably carcinogenic in 2007), and mood disorders. Mechanisms include cortisol dysregulation, insulin resistance, and immune impairment. Even mild "social jet lag" — weekday/weekend sleep shifts of 1-2 hours — correlates with worse health outcomes in epidemiological studies.