Depression circadian changes

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. 

Perturbation of the 5-HT system can elicit changes in a wide variety of behaviors. Furthermore, drugs that act on serotonergic neurons and their receptors are used to treat diseases such as depression, anxiety disorders and schizophrenia. Thus, 5-HT has been implicated in the regulation of many behaviors and physiological processes. The involvement of 5-HT in three areas - neuroendocrine function, circadian rhythms and feeding behavior - will be highlighted for illustrative purposes. 

Several studies have show n increased plasma levels of IL-6 in patients with MDD. In a more extensive study, Alesci and colleagues found that IL-6 levels were increased in MDD patients throughout the circadian cycle (Alesci et al., 2005). There was a 12-hour shift in the circadian rhythm of IL-6 plasma levels and its complexity was reduced. Even though IL-6 is a known activator of the HPA axis, cortisol levels were not consistendy changed in MDD padents compared to controls. Addidonally, it v as found that IL-6 levels, with their altered rhythm, correlated significandy with mood radngs. IL-6 also induces a sickness behavior very similar to depression. These data suggest a direct reladonship betw een IL-6 and depression. 

Depressive states can alter significantly the basal rates of pituitary hormone secretion and their circadian rhythms. In fact, depression may be related to periods when hormonal rhythms are out of phase with other rhythms in the body. Circulating levels of sleep-inducible hormones (GH, PRL, LH) are lower in depressive states, whereas that of ACTH is elevated. The basal level of ACTH in a depressed individual is elevated to the extent that it flattens the circadian oscillations of the hormone. These changes resemble those seen during disruptive phase shifts (e.g., east-bound trip, altered work schedule, etc.) and emphasize the importance of CNS influence on the release of anterior pituitary hormones. 

The permissive serotonin hypothesis proposes that serotonin (5-hydroxytryptamine or 5-HT) plays a critical role in modulating brain activity (e.g., stabilization of the catecholamine system and inhibition of dopamine [DA] release), and is low in both mania and depression. L-tryptophan or 5-HT deficiency and changes in the light-dark cycle may result in reduced melatonin secretion from the pineal gland that disrupts the sleep-wake cycle, alters circadian rhythms, and causes seasonal affective changes. ... 

The body s internal molecular timekeeper, known as the circadian clock, regulates cycles of sleep and wakefulness. When it is out of sync, it can cause disorders such as jet lag and depression. Conventional time-of-day measurements are based on the changing position of the Sun in the sky, but shifts in the positions of stars can also be used to define a kind of time known as sidereal time. One sidereal day lasts a few minutes less than one solar day. 

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