Circadian rhythm disruption

Sleepiness is a primary symptom of narcolepsy, often preceding the onset of the other well-known symptoms of the disease, namely cataplexy, sleep paralysis, and hypnagogic hallucinations (44). Evaluation of the MSLT of narcoleptic patients has demonstrated a short sleep latency (<5 min) and multiple sleep-onset REM periods (SOREMPs). The more specific finding in the MSLT of narcoleptic patients is more than 2 SOREMPs, shown to reach a specificity of 99% by Amira et al. (45), which further increased to 99.2% if 3 SOREMPs were recorded (46). On the other hand, more than one SOREMP can occur in nonnarcoleptic patients, such as those with sleep apnea, sleep deprivation, depression, periodic limb movements, circadian rhythm disruption, or withdrawal from REM-suppressing medications (5,47). Thus, the findings of the MSLT, which is always performed for suspected narcoleptic patients, must be interpreted in view of the clinical history and nocturnal PSG. 

There are two concerns about the effects of shift rotation and night work disruption of "circadian rhythms" and sociological costs, that is, effects on the worker s family life. 

Studies by Smith et al. (1982), Folkard et al. (1979), and Colquhoim et al. (1969), have investigated the disruption of circadian rhythms caused by having to be awake and work at imusual hours and by having to sleep during daytime. With respect to the sociological effects, studies by Kasl (1974) and Kahn (1974) concluded that fixed afternoon and night shifts lead to lower levels of social satisfaction because it becomes difficult to participate in family activities. 

Poor Timing of Neurotransmission. The activity of some brain circuits, like the secretion of certain hormones, varies at certain times of the day. Called circadian rhythms, the timing of these rhythms may be disrupted in some illnesses. Examples include sleep disorders such as insomnia and narcolepsy, as well as other conditions such as nighttime binge-eating disorder. 

Both clinical and experimental studies have shown that a number of transmitter receptors and amine transport processes show circadian changes. It is well established that depression is associated with a disruption of the circadian rhythm as shown by changes in a number of behavioural, autonomic and neuroendocrine aspects. One of the main consequences of effective treatment is a return of the circadian rhythm to normality. For example, it has been shown that the 5-HT uptake into the platelets of depressed patients is largely unchanged between 0600 and 1200 hours, whereas the 5-HT transport in control subjects shows a significant decrease over this period. The normal rhythm in 5-HT transport is only reestablished when the depressed patient responds to treatment. Thus it may be hypothesized that the mode of action of antidepressants is to normalize disrupted circadian rhythms. Only when the circadian rhythm has returned to normal can full clinical recovery be established. 

Muscarinic Ml receptor CHRMl Agonism May increase blood pressure, heart rate and sympathetic outflow — May be involved in the regulation of circadian rhythm. Antagonism Disruption of cognitive functions such as learning and memory. 

Somers DE, Devlin PF, Kay SA 1998 Phytochromes and cryptochromes in the entrainment of th Arabidopsis circadian clock. Science 282 1488-1490 Stanewsky R, Kaneko M, Emery P et al 1998 The cryb mutation identifies cryptochrome as a circadian photoreceptor in Drosophila. Cell 95 681-692 Wang ZY, Tobin EM 1998 Constitutive expression of the CIRCADIAN CLOCK ASSOCIATED 1 CCAl gene disrupts circadian rhythms and suppresses its own expression. Cell 93 1207-1217... 

Allada R, White NE, So WV, Hall JC, Rosbash M 1998 A mutant Drosophila homolog of mammalian Clock disrupts circadian rhythms and transcription of period and timeless. Cell 93 791-804... 

FIG. 3. Disruption of the circadian rhythm of sleep—wake behaviour by infusion of TGFa into the 3rd ventricle. The effects were highly reproducible (controls, = 3 TGFa, = 5). Data are displayed in 1 h bins. 

People and animals follow a natural circadian rhythm. Humans and many animals tend to be diurnal. They get up in the morning, are active during the day, and sleep at night. Disruptions in this natural cycle can be difficult. With the advent of air travel, people could... 

Education creates the critical foundation for all other AMP activities. The educational component should include accurate, scientifically valid information on, at a minimum, the basics of sleep and circadian rhythms, and the risks associated with their disruption. A model Alertness Management educational module is... 

There is emerging evidence that OSA may be a pro-inflammatory disorder with elevated circulating cytokines [60]. Abdominal visceral fat is a major reservoir of cytokines, and obesity is a leading risk factor for the presence of OSA [60], The mechanism(s) whereby pro-inflammatory cytokines are elevated in OSA is not fully elucidated, but may be related to the excessive sympathetic nervous system activation notable in OSA. Tumor necrosis factor (TNF)-a and interleukin (IL)-6 levels are elevated in OSA [61,62] and the circadian rhythm of TNF-a is disrupted in OSA [63]. IL-6 levels are higher again in OSA patients with systemic hypertension compared to normotensive apneics [60], IL-6 levels return to normal in OSA patients treated effectively with CPAP [64]. Other mediators of inflammation elevated in OSA include intercellular adhesion molecule-1 and C-reactive protein, the latter being synthesized primarily in hepatocytes in response to IL-6 [60], The presence of these and other pro-inflammatory cytokines may link to the increased prevalence of cardiovascular morbidity in OSA. 

Perez-Lloret S, Aguirre AG, Cardinali DP, Toblli JE (2004) Disruption of ultradian and circadian rhythms of blood pressure in nondipper hypertensive patients. Hypertension 44 311-315... 

Multiple links exist between circadian rhythms and cancer. First, the rate of tumor growth in rodents increases as a result of (a) mutations affecting the circadian clock [1] and (b) disruption of the neural pacemaker governing circadian rhythms [2], Second, the cell cycle is directly controlled by the circadian clock [3-5]. This explains why progression through the cell cycle often displays a strong circadian dependence [6-9]. Third, the link between the circadian clock and cancer is further illustrated by the effect of circadian rhythms on a variety of anticancer medica-... 

The time of falling asleep is determined by three factors, which in normal sleepers occur at bedtime. These are (a) circadian rhythm, i.e. the body s natural clock in the hypothalamus triggers the rest/ sleep part of the sleep-wake cycle, (b) tiredness, i.e. time since last sleep, usually about 16 hours and (c) lowered mental and physical arousal. If one of these processes is disrupted then sleep initiation is difficult, and it is these three factors that are addressed by a standard sleep hygiene program (see below). Early in the course of insomnia rigorous adherence to sleep hygiene principles alone may restore the premorbid sleep pattern but in some patients the circadian process is less stable and they are less susceptible to these measures. 

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