Figure 3. Circadian disruption at different levels.

First, at a systemic level, circadian disruption occurs when environmental cycles (black square wave, e.g., light/dark cycle; which we refer to as “environmental misalignment”) and/or behavioral cycles (green square wave, e.g., sleep/wake, fasting/feeding, rest/activity cycle; “behavioral misalignment”) are misaligned relative to the central clock in the SCN (red cosine). Alternatively, exposure to light at night can shift the central clock, which can cause misalignment of the central clock with the behavioral cycle if the behavioral cycle doesn't shift, which may occur in an intensive care unit. Second, at an organismal level, circadian disruption can be caused by internal misalignment (also called “internal desynchrony”) between the central clock and peripheral clocks (blue cosine), which can be induced by, e.g., misaligned eating (although direct evidence in humans is missing). It also refers to misalignment among peripheral clocks in different organs, where peripheral clocks are in abnormal phase relationships with each other. At a tissue level, circadian disruption can be caused by desynchronization among cells within a tissue (clocks in each individual organs and/or cells are represented as black cosine) Finally, at cellular level, expression of clock genes should also follow particular phase relationships that can be disturbed. Note that the illustrated phases of the cosine/square wave curves in the Figure does not necessarily convey the time of the highest levels, but conveys a conceptual illustration of alignment (when the acrophases, or timing of peaks, occur at an optimal phase relationship) versus misalignment (when the relationships between acrophases are abnormal).