Contemporary chronobiology: studies and scientific references

The 2017 prize in Physiology or Medicine was awarded jointly to three researchers: Jeffrey C. Hall, Michael Rosbash and Michael W. Young.

The official citation reads, word for word: for their discoveries of molecular mechanisms controlling the circadian rhythm. Medicine's highest recognition went to the study of biological clocks.

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A review pulling together what sequencing techniques have revealed inside the mammalian circadian clock, from single genes to the whole genome.

The clock is a feedback loop: certain genes produce proteins which, as they build up, switch off the very genes that produced them, and the cycle starts again. The targets of this mechanism are spread across the genome and tied to the regulation of metabolism, cell growth and physiology.

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A review of how the circadian system is organised in mammals: how the central clock in the brain relates to the ones scattered through the rest of the body.

The system is a hierarchy. In the suprachiasmatic nucleus of the hypothalamus a coupled population of neurons acts as the body's master pacemaker, driving activity and rest, feeding, body temperature and hormones. In most other cells of the body there are self-sustaining clocks, woven into metabolic pathways.

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The authors applied an algorithm able to reconstruct the temporal order of samples even when the time of collection is unknown, across thirteen tissues from 632 human donors.

Nearly half of protein-coding genes turn out to cycle in at least one of the thirteen tissues. A thousand of those genes encode drug targets, or proteins that transport or metabolise drugs, which makes the timing of a dose a variable that can matter clinically.

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The authors measured gene expression in white blood cells and adipose tissue, comparing samples collected in different seasons and different countries, from the United Kingdom to The Gambia, from Europe to Oceania.

More than 4,000 protein-coding genes show a seasonal expression profile, and the profiles invert between Europe and Oceania. The cellular make-up of blood also shifts with the season. Through the European winter the immune system shows an inflammatory profile, with higher levels of soluble interleukin-6 receptor and C-reactive protein.

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One person underwent functional MRI and blood draws every day for thirty consecutive days, tracking hormones and brain network organisation together. The study was repeated a year later.

Oestrogen and progesterone are associated with widespread changes in brain connectivity. Time-lagged analysis suggests hormonal shifts precede changes in cortical networks, particularly the Default Mode and Dorsal Attention networks, whose hubs are dense with oestrogen receptors. The same pattern reappeared in the follow-up round.

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The authors built a questionnaire, the Munich ChronoType Questionnaire, asking when people sleep on work days and on free days. They ran it with more than 55,000 people and validated it against sleep logs, actigraphy and physiological measures.

Sleep and wake times do not split into two groups: they spread along a continuous, near-Gaussian curve. At the extremes, the earliest types wake up as the latest types are falling asleep. Timing and duration of sleep are generally independent, but analysed separately for work and free days, duration depends strongly on chronotype.

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A large-scale epidemiological study relating body mass index to the mismatch between the body clock and social schedules, what the authors call social jetlag.

Beyond sleep duration, social jetlag is associated with a higher body mass index. The authors conclude that living against your own clock may contribute to the spread of obesity, and draw implications for daylight saving time and for school and work schedules.

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A systematic review with meta-analysis: 477 references screened, 43 studies meeting the inclusion criteria, for a total of 231,648 people.

The association between social jetlag and adiposity measures is positive and consistent in direction, but small in size: the coefficient for body mass index is 0.12. Heterogeneity between studies is very high, and the authors call for further work to establish causality.

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A pre-registered systematic review across three databases, covering studies that measured maximum endurance or strength at a minimum of three different times of day. Of 10,460 articles screened, 63 were included and 29 entered the meta-analysis.

Performance varies across the day, in favour of the evening. Effect sizes range from 0.23 for endurance tests to 0.79 for jump height, with 0.73 for maximum power output and 0.39 for handgrip strength.

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The authors combined an athlete-specific chronometric test, extended circadian analysis and repeated physical testing, to work out what actually drives the moment of peak performance.

The best predictor of peak timing is not the hour on the clock: it is time since waking. The best moments differ between early and late types, and the same athlete's performance varies by as much as 26% across a single day.

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A review of studies on how sleep pressure, circadian variation and chronotype affect cognitive performance in healthy people.

Time of day modulates a wide range of tasks: attention, executive function and memory. The effect depends on chronotype, and specifically on the synchrony between a person's peak arousal period and the hour at which they are tested. The authors conclude that test timing should be accounted for in both clinic and research.

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56 healthy volunteers, classified as early (25) or late (31) chronotypes through questionnaire, circadian phase markers and actigraphy, were measured at 2pm, at 8pm and at 8am the following morning.

The two groups show different profiles across the day for daytime sleepiness, psychomotor vigilance, executive function and isometric grip strength. Late chronotypes come out impaired in the morning compared with early ones.

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The authors analysed the emotional content of millions of public messages written on a social platform by people across cultures worldwide.

Mood follows a daily arc: people wake up in a good mood and it deteriorates as the day goes on, consistent with the effects of sleep and circadian rhythm. Baseline positive affect changes with daylength over the year. At weekends people are happier, and the morning peak arrives two hours later.

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A methodological review of ecological momentary assessment: repeatedly sampling behaviour and experience in the moment they happen, in the person's own environment, using diaries, phones or sensors.

Classical clinical assessment relies on retrospective self-reports collected at visits, limited by recall bias and poorly suited to capturing how behaviour changes over time and across contexts. Sampling in the moment reduces that bias and increases ecological validity.

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A review of the history, motivation and design of n-of-1 trials, those in which a single individual is the sole unit of observation.

These trials can use the same instruments as population studies: randomisation, washout periods, crossovers and placebo controls. They remain little used in clinical practice, but the authors argue that wearable monitoring devices now make running them far more practical.

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