title: Delayed onset of the diurnal melatonin rise in patients with Huntington's disease.
abstract: Sleep disturbances are very prevalent in Huntington's disease (HD) patients and can substantially impair their quality of life. Accumulating evidence suggests considerable dysfunction of the hypothalamic suprachiasmatic nucleus (SCN), the biological clock, in both HD patients and transgenic mouse models of the disease. As melatonin has a major role in the regulation of sleep and other cyclical bodily activities and its synthesis is directly regulated by the SCN, we postulated that disturbed SCN function is likely to give rise to abnormal melatonin secretion in HD. Therefore, we compared 24 h melatonin secretion profiles between early stage HD patients and age-, sex- and body mass index-matched controls. Although mean diurnal melatonin levels were not different between the two groups (p = 0.691), the timing of the evening rise in melatonin levels was significantly delayed by more than 01:30 h in HD patients (p = 0.048). Moreover, diurnal melatonin levels strongly correlated with both motor (r = -0.70, p = 0.036) and functional impairment (r = +0.78, p = 0.013). These findings suggest a delayed sleep phase syndrome-like circadian rhythm disorder in early stage HD patients and suggest that melatonin levels may progressively decline with advancing disease.
authors: Department of Neurology, K-05-Q 110, Leiden University Medical Center, P.O. Box 9600, Albinusdreef 2, 2300 RC Leiden, The Netherlands. n.a.aziz@lumc.nl
authors: N Ahmad
authors: NA
authors: Aziz
authors: Hanno
authors: H
authors: Pijl
authors: Marijke
authors: M
authors: Frölich
authors: Janny P
authors: JP
authors: Schröder-van der Elst
authors: Chris
authors: C
authors: van der Bent
authors: Ferdinand
authors: F
authors: Roelfsema
authors: Raymund A C
authors: RA
authors: Roos
mesh_terms: D021081:Chronobiology Disorders / Q000097:blood / Q000209:etiology / Q000378:metabolism*; D002940:Circadian Rhythm / Q000502:physiology*; D018450:Disease Progression; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000150:complications / Q000378:metabolism*; D008297:Male; D008550:Melatonin / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*; D008875:Middle Aged; D012893:Sleep Wake Disorders / Q000097:blood / Q000209:etiology / Q000378:metabolism*; D013997:Time Factors
chemical_list: D008550:Melatonin