Clinical Chronobiology: A Timely Consideration in Critical Care Medicine

Helen McKenna; Gijsbertus T. J. van der Horst; Irwin Reiss; Daniel Martin


Crit Care. 2018;22(124) 

In This Article


Circadian rhythm disruption can be genetic or acquired, and its impact extends far beyond the fleeting symptoms of jet lag (Table 1), reflecting the range of functions which follow a circadian rhythm. Chronic circadian rhythm disruption has been linked with diverse pathologies, from metabolic disorders, obesity, diabetes, cardiovascular disease and cancer.[18,19,20,21] Genetic disruption results from mutations of the clock genes responsible for generating the cellular circadian rhythm. Such mutations result in a spectrum of sleep pattern disorders.[22] Given that clock genes regulate cell proliferation, metabolism, DNA repair and apoptosis, it is of no surprise that polymorphisms in these genes (including PER1 and PER2) have been associated with cancer in both mouse models and humans.[23]CLOCK gene mutations have been implicated in the development of obesity in humans and may play a key role in metabolic syndrome, type 2 diabetes and cardiovascular disease.[24,25] Alterations within clock genes are also related to alcohol consumption[26] and recreational drug rewarding in animal models,[27] indicating the far-reaching consequences of disruption to this fundamental regulatory system.

Environmental Clock Disruption

Living out of phase with one's body clock will also induce circadian dysrhythmia, and has also been shown to result in pathology.[28] Night shifts create a complete inversion of the sleep–wake cycle, analogous to travelling across 12 time zones. Night shift workers have been found to have higher rates of a number of behavioural and health-related morbidities[29] including sleep disorders, obesity,[30] metabolic syndrome[31] and cancer.[32,33] Sleep restriction also disrupts the circadian rhythm and has a profound effect on metabolic control in healthy volunteer subjects.[34] We are currently facing an epidemic of environmental circadian rhythm disturbance, as modern work and social schedules forces people to live contrary to their chronotype (social jet lag).[35]