Chronodisruption: Origin, Roots, and Developments of an 18-Year-Old Concept. Comment on Desmet et al. Time-Restricted Feeding in Mice Prevents the Disruption of the Peripheral Circadian Clocks and Its Metabolic Impact during Chronic Jetlag. Nutrients 2021, 13, 3846

We read with interest the article by Desmet and colleagues entitled “Time-Restricted Feeding in Mice Prevents the Disruption of the Peripheral Circadian Clocks and Its Metabolic Impact during Chronic Jetlag” [1]. A key focus is “chronodisruption”—used some 18 times as “a disruption of the circadian system”—and the authors refer to “chronodisruptors”, for which they include a reference [2]. Since chronodisruption (CD) itself is not explicitly referenced, may we complement their work with publications in which the concept was first proposed in 2003 [3] and systematically developed thereafter?

More generally, CD was conceptualized as a relevant disruption of an otherwise beneficial circadian organization of physiology, endocrinology, metabolism, and behavior by ordered sequences of biological rhythms during sleep and wake cycles. Since the term was coined [3], CD was—step-by-step—put into thematic and historical context with Pittendrigh’s insights as a nestor of modern chronobiology [2,4], included in cancer theory development [5], investigated in shift workers [5,6,7] and flight personnel [6], defined in further detail [2], operationalized as split nexus of internal and external times [8], included in metrics to compute CD doses (Computing chronodisruption—Computing circadian misalignment—Computing sleep deficiency) [7,9,10], contrasted with the concept of social jetlag [9,10], and conceptualized as a ubiquitous causal phenomenon at both work and play [11] (

Table 1. Origin, roots, and developments of the term and concept of chronodisruption.

References
1960 [4]	Pittendrigh, C.S. Circadian rhythms and the circadian organization of living systems. Cold Spring Harbor Symposia on Quantitative Biology
2003 [3]	Erren, T.C.; Reiter, R.J.; Piekarski, C. Light, timing of biological rhythms, and chronodisruption in man. Naturwissenschaften
2008 [5]	Erren, T.C.; Reiter, R.J. A generalized theory of carcinogenesis due to chronodisruption. Neuroendocrinology Letters
2008 [6]	Erren, T.C.; Pape, H.G.; Reiter, R.J.; Piekarski, C. Chronodisruption and cancer. Naturwissenschaften
2009 [2]	Erren, T.C.; Reiter, R.J. Defining chronodisruption. Journal of Pineal Research
2013 [8]	Erren, T.C.; Reiter, R.J. Revisiting chronodisruption: when the physiological nexus between internal and external times splits in humans. Naturwissenschaften
2014 [7]	Erren, T.C.; Morfeld, P. Computing chronodisruption: how to avoid potential chronobiological errors in epidemiological studies of shift work and cancer. Chronobiology International
2017 [9]	Erren, T.C.; Morfeld, P.; Lewis, P. Computing circadian misalignment: Why not combine sleep timing and duration to assess accumulated sleep deficiency? Chronobiology International
2018 [10]	Erren, T.C.; Gross, J.V.; Lewis, P. Computing sleep deficiency. Journal of Sleep Research
2019 [11]	Erren, T.C.; Lewis, P. Hypothesis: ubiquitous circadian disruption can cause cancer. European Journal of Epidemiology

). Beyond epidemiological contexts, the CD concept is increasingly used, and explored, in experimental research and in more and more journals [12,13].

Clearly, we appreciate the work by Desmet and colleagues. Equally clearly, that CD is a widely used and useful concept is also evinced by citation statistics: as of 3 December 2021, Web of Science indicates that publications that explicitly regard the topic chrondisruption accumulate an h-index of 40 [14].

Overall, that our internal 24 h (circadian) timing systems coordinate countless fundamental physiological processes and that their disruptions may lead to adverse health effects such as obesity [15], diabetes, cardiovascular disease, kidney disease [16], psychiatric disorders, detrimental pregnancy outcomes [17], and, plausibly, cancer [18] can make chronodisruption a prime target for research. An appropriate way to facilitate learning about, challenging, falsifying, or expanding the concept of CD may be to offer source references for its origin [3], roots, and developments (such as in Table 1, [16], and this comment).