Circadian misalignment and health

Abstract

Circadian rhythms are near 24-h patterns of physiology and behaviour that are present independent of external cues including hormones, body temperature, mood, and sleep propensity. The term 'circadian misalignment' describes a variety of circumstances, such as inappropriately timed sleep and wake, misalignment of sleep/wake with feeding rhythms, or misaligned central and peripheral rhythms. The predominance of early research focused on misalignment of sleep to the biological night. However, discovery of clock genes and the presence of peripheral circadian oscillators have expanded the definitions of misalignment. Experimental studies conducted in animal models and humans have provided evidence of potential mechanisms that link misalignment to negative outcomes. These include dysregulation of feeding behaviours, changes in appetite stimulating hormones, glucose metabolism and mood. This review has two foci: (1) to describe how circadian misalignment has been defined and evaluated in laboratory and field experiments, and (2) to describe evidence linking different types of circadian misalignment to increased risk for physical (cardiovascular disease, diabetes, obesity, cancer) and psychiatric (depression, bipolar, schizophrenia, attention deficit) disorders. This review will describe the role of circadian misalignment as a risk factor for disease in the general population and in clinical populations, including circadian rhythm sleep disorders and psychiatric disorders.

Figure 1. Representation of Central and Peripheral Circadian Rhythms

This figure depicts the relationship between central and peripheral circadian rhythms. Circadian genes are present in every cell in the body. The central circadian rhythm is generated by the suprachiasmatic nucleus. The light/dark cycle is one of the main entraining agents for the central rhythm. Peripheral rhythms are present in cells, organs and organ systems. The coordination between the central and peripheral rhythms is not fully understood but involves hormonal, neurologic and behavioral pathways. Misalignment can occur when the central rhythm is misaligned to the light/dark cycle or when central and peripheral rhythms are misaligned.

Figure 2. Circadian Phase and Phase Angle between Melatonin and Sleep

The curved lines depict examples of the nocturnal melatonin rhythm in individuals with normal phase (solid line) and phase delay (dotted line). The bars below indicate the sleep periods in normal phase (black bar) and phase delay (gray bar). Phase angles between dim light melatonin onset (DLMO) and midpoint of sleep are depicted with lines and arrows. Compared with the normal alignment, the phase delayed example demonstrates a later DLMO and a shorter duration or phase angle between DLMO with sleep onset and midpoint of the sleep period.