Melatonin secretion

Figure 22.3 Possible links in the induction of circadian rhythm between daylight, the suprachiasmatic nucleus and melatonin release from the pineal gland. Some fibres in the optic nerve, projecting from the eye to the lateral geniculate nucleus (LGN) in the thalamus, innervate the suprachiasmatic nucleus (SCN) in the anterior hypothalamus, via the retinohypothalamic tract (RHT). Others project to the SCN from the LGN in the geniculohypothalamic tract (GHT). The release of melatonin into the circulation from the pineal gland (PG) is maximal at night and appears to be controlled partly by noradrenaline released from sympathetic nerves originating in the superior cervical ganglion (SCG). Melatonin receptors are found in the SCN, the removal of which dampens melatonin secretion...

Figure 22.9 Summary of the influence of varying factors on sleep and waking. The EEG is shown diagramatically in the typical arousal (awake) state and in both non-REM (slow wave) and REM sleep. Appropriate activity levels, high or low, are shown for the different factors such as light input, melatonin secretion or ACh, NA, and 5-HT function in the different phases...

Melatonin secretion is synchronized to the light/dark (LD) cycle, with a nocturnal maximum (in young humans, about 200 pg/ml plasma) and low diurnal baseline levels (about 10 pg/ml plasma). Studies have supported the value of the exogenous administration of melatonin in circadian rhythm sleep disorders, insomnia, cancer, neurodegenerative diseases, disorders of the immune function, and oxidative damage (Karasek et al. 2002 Pandi-Perumal et al. 2005, 2006 Srinivasan et al. 2005a,b, 2006 Hardeland et al. 2006). 

The circadian pattern of pineal NAT activity and consequently melatonin secretion is controlled by the suprachiasmatic nuclei (SCN) as it is abolished by lesions of the SCN, the major circadian oscillator (Klein and Moore 1979). Thus, the environmental L/D cycle acts as the pervasive and pre-eminent Zeitgeber that regulates melatonin synthesis (Scheer and Czeisler 2005). 

Brismar, K., Hylander, B., Eliasson, K., Rossner, S. Wetterberg, L. (1988). Melatonin secretion related to side-effects of beta-blockers from the central nervous system. Acta Med. Scand. 223, 525-30. 

Brismar, K Mogensen, L. Wetterberg, L. (1987). Depressed melatonin secretion in patients with nightmares due to beta-adrenoceptor blocking drugs. Acta Med. Scand. 221, 155-8. 

The melatonin hypothesis postulates that winter depression is triggered by alterations in nocturnal melatonin secretion, which acts as a chemical signal of darkness. Thus, by giving light therapy before dawn or after dusk, the light period can be prolonged and secretion of melatonin can be diminished. Evidence that atenolol, which suppresses melatonin secretion, was not an effective therapy for SAD weakens this particular hypothesis ( 148). 

There was suppression of endogenous melatonin secretion in two of five patients with bipolar disorder after 12 weeks of treatment with high-dose melatonin (10 mg/day)... 

There was suppression of endogenous melatonin secretion in two of five patients with bipolar disorder after 12 weeks of treatment with high-dose melatonin (10 mg/day) (19). One woman developed an unentrained sleep-wake cycle after melatonin was withdrawn (not previously a feature of her illness), which persisted for several months. 

Involuntary movements of the lip and tongue, restlessness, and insomnia developed twice when chronic melatonin therapy was abruptly withdrawn in a young woman with cerebral palsy these symptoms resolved when melatonin was restarted, but did not recur with gradual withdrawal over 2 months (13). This again suggests that endogenous melatonin secretion is suppressed after chronic use. 

Potentized homeopathic medicines have preferential action on sides of the body some are more effective on one side than on the other. This differential effect of the medicines with respect to laterality can be traced to functional asymmetry of the human brain. The brain can asymmetrically modulate nurochemical, neuroendocrine and immune reactivity. Potentized drugs are very often selected on the basis of time modalities of symptoms of a disease. The time modalities of the drug action can be correlated with the internal clock or biological rhythms of organisms which are disturbed in diseased conditions. Melatonin, secreted in the brain, has marked influence on the circadian rhythms. 

While everyone follows this general pattern of diurnal melatonin secretion, each individual has his or her own unique pattern. Melatonin peaks and valleys can occur at different times in different people and may explain why some individuals are morning people, while others are night owls. ... 

PLMS, PLMW and leg sensory discomfort have a similar circadian profile, as do subjective complaints of RLS patients. The changes in melatonin secretion preceding the increase in sensory and motor symptoms in RLS patients seem to suggest that melatonin may be implicated in a worsening of RLS in the evening and at night, through a possible inhibitory effect on central dopamine secretion [15],... 

Mishima K, Tozawa T, Satoh K, MatsumotoY, HishikawaY, Okawa M (1999) Melatonin secretion rhythm disorders in patients with senile dementia of Alzheimer s type with disturbed sleep-waking. Biol Psychiatry 45 417-421... 

SSRIs can cause insomnia and daytime somnolence however, the symptoms seem to reflect a sleep-wake cycle disorder. It is conceivable that disruptions in the normal pattern of melatonin secretion, particularly a delay in the normal early morning fall in plasma concentrations could be involved in the pathophysiology of these symptoms. The fact that fluvoxamine is the SSRI that is most likely... 

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