Circadian Rhythms

The SCN is a paired nucleus of ~20,000 neurons located in the anterior hypothalamus, directly above the optic chiasm. It is the master pacemaker because: (1) SCN lesions in animals abolish circadian rhythmicity in sleep, locomotor activity, and hormone secretion; (2) SCN transplants from donors with different circadian periods confer the donor's period on the recipient; (3) SCN neurons maintain autonomous circadian firing rhythms in culture, independent of other brain areas. The SCN receives direct light input from the retina via the retinohypothalamic tract and transmits timing signals to peripheral clocks throughout the body via neural (autonomic), humoral (including vasopressin and prokineticin 2), and temperature signals.

Melatonin is an indoleamine hormone synthesised from serotonin in the pineal gland under circadian control from the SCN. Its secretion is strongly suppressed by light (especially blue ~480 nm light, via ipRGCs) and peaks in darkness — typically from about 9 pm to 4 am. It acts as a hormonal signal of biological night, coordinating the timing of circadian-driven physiology: it promotes sleep onset by reducing core body temperature and alertness, synchronises peripheral clocks, and facilitates circadian resetting after jet lag. It is not a strong sleep-inducer in already-entrained individuals but can shift the phase of the clock — low doses (0.5 mg) taken in the morning advance the clock; taken in the evening, they delay it. It does not directly produce deep or sustained sleep the way adenosine does.

Social jetlag refers to the discrepancy between an individual's biological sleep timing (dictated by their chronotype) and the socially imposed schedule of work, school, or social obligations. People with late chronotypes who must wake early for school or work chronically experience this mismatch — analogous to repeated transatlantic jet lag. Wittmann et al. (2006) showed that social jetlag is associated with smoking, higher alcohol and caffeine consumption, and overweight status, independent of sleep duration. Adolescents with late chronotypes attending early-start schools show impaired cognitive performance in morning classes. Interventions delaying school start times have demonstrated improvements in academic performance and mental wellbeing.

Light is the dominant zeitgeber. Short-wavelength blue light (~480 nm) detected by melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) — distinct from rod and cone photoreceptors — projects via the retinohypothalamic tract directly to the SCN. Light in the early evening suppresses melatonin and delays the circadian phase (pushes sleep later); light in the early morning advances the phase (pushes sleep earlier). The response to light is most pronounced during the "sensitive window" in the biological night (~8 hours of biological night after melatonin onset). This is why evening screen use (which emits blue light) delays sleep timing, and why morning bright-light therapy is used to advance circadian phase in delayed sleep phase disorder and seasonal affective disorder.