Circadian disruption: What do we actually mean?

Abstract

The circadian system regulates physiology and behavior. Acute challenges to the system, such as those experienced when traveling across time zones, will eventually result in re-synchronization to local environmental time cues, but this re-synchronization is oftentimes accompanied by adverse short-term consequences. When such challenges are experienced chronically, adaptation may not be achieved, as for example in the case of rotating night shift workers. The transient and chronic disturbance of the circadian system is most frequently referred to as "circadian disruption", but many other terms have been proposed and used to refer to similar situations. It is now beyond doubt that the circadian system contributes to health and disease, emphasizing the need for clear terminology when describing challenges to the circadian system and their consequences. The goal of this review is to provide an overview of the terms used to describe disruption of the circadian system, discuss proposed quantifications of disruption in experimental and observational settings with a focus on human research, and highlight limitations and challenges of currently available tools. For circadian research to advance as a translational science, clear, operationalizable, and scalable quantifications of circadian disruption are key, as they will enable improved assessment and reproducibility of results, ideally ranging from mechanistic settings, including animal research, to large-scale randomized clinical trials.

Keywords: chronic disease; chronotype; circadian desynchronization; circadian desynchrony; circadian misalignment; social jetlag.

Figure 1.. Forty years of circadian disruption terminology on Pubmed (https://www.ncbi.nlm.nih.gov/pubmed/; 1964–2018).

The search was conducted on July 5^th 2018 and used the respective terms in quotation marks (i.e., “circadian disruption”). The absolute frequency is plotted across years.

Figure 2.. Circadian Disruption in laboratory and field settings.

The left panel displays potential causes of disruption and how they might differ between laboratory and field settings. On the upper part of the right panel, sample variability of the study population is illustrated. While laboratory studies usually target specific populations in a smaller number of individuals, field studies include larger and more heterogeneous samples. Both approaches are valid. Laboratory studies minimize noise in the signal by selecting homogenous samples, and thereby can detect even small effects. However, generalizability is limited. The resulting levels of disruption (lower right panel) should this differ between laboratory and field settings, with high contrast conditions and little inter-individual variability in laboratory settings, and higher variability in field ones. In view of our improved understanding of circadian organization, including the relevance of peripheral clocks, future work is needed to harmonize conceptual approaches and operationalization of circadian disruption in the context of mechanistic, observational and intervention studies. Figure credit: Olivia Walch, PhD, twitter: @oliviawalch).