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Dim Light Melatonin Onset (DLMO)

Dim Light Melatonin Onset (DLMO) is of vital importance for both diagnosis and treatment of circadian rhythm disorders.

DLMO is usually defined as the time at which salivary melatonin reaches 4 pg / ml (or when blood melatonin reaches 10 pg / ml). DLMO is considered as the best clinically useful characteristic of the 24 hour melatonin rhythm 1

Diagnosis
Endogenous melatonin, a hormone produced by the pineal gland during the dark phase of the day-night cycle, synchronizes circadian rhythms,  especially the sleep-wake rhythm. Its secretion is controlled by an endogenous oscillator that is entrained by light. When  endogenous melatonin starts to rise late, sleep wake rhythm is delayed. When endogenous melatonin starts to rise early, sleep wake rhythm is advanced. When melatonin onset fluctuates, usually sleep-wake rhythm fluctuates too 2.
The phase of the melatonin rhythm is a little more than 24 h. Light entrains the melatonin rhythm to a 24-h rhythm. Consequently totally blind people may have a free running melatonin and sleep-wake rhythm. 
Melatonin rhythm correlates strongly with circadian rhythms. Therefore  DLMO is the most useful parameter to establish circadian rhythm disorders.

Treatment
Both melatonin and bright light may shift endogenous melatonin rhythm and consequently sleep-wake rhythm.  The time of the direction of the shift depends of the time at which these interventions are applied.

Exogenous melatonin, administered 5 hours before DLMO advances endogenous melatonin rhythm (and consequently sleep-wake rhythm) most powerfully.   Melatonin administered 10 hours after DLMO delays endogenous melatonin rhythm (and consequently sleep wake rhythm) most powerfully.

Bright light, administered during the upward melatonin curve delays melatonin rhythm (and consequently sleep-wake rhythm). Bright light administered during the downward melatonin curve advances melatonin rhythm and consequently sleep-wake rhythm.

Consequently DLMO is of vital importance for optimal treatment of circadian rhythm disorders with bright light and melatonin.

Circadian sleep-wake rhythm disorders.

Several sleep-wake rhythm disorders have been described:

  • Delayed sleep phase syndrome (DSPS)
    DSPS is characterized by extreme difficulty to initiate sleep at a conventional hour of the night and great difficulty to wake up on time in the morning for school or work.
  • Advanced sleep-wake syndrome (ASPS)
    ASPS is the opposite of DSPS. ASPS is characterized by an extreme difficulty to stay awake in the evening and waking up wide-awake early in the morning  
  • Irregular sleep-wake rhythm.
    The irregular sleep-wake rhythm is characterized by stark fluctuating sleep onset and sleep offset
  • Free running sleep-wake rhythm
    The free running sleep-wake rhythm is characterized by sleep onset and sleep offset occurring each next day later
  • Shift maladaptation syndrome
    The shift maladaptation syndrome occurs in shift workers. It is characterized by chronic sleep disturbance and waking fatigue, gastrointestinal symptoms. Usually after a night shift it takes many days to get back a normal sleep-wake rhythm.
  • Jet-lag
    Jet-lag is characterized by a disturbed sleep-wake rhythm following a flight which passed several time zones.

Other diseases associated with  circadian sleep-wake rhythm disorders.

Several disorders are associated with a disturbed circadian sleep-wake rhythm:

  • Chronic idiopathic sleep onset insomnia in children 3;4
  • Chronic sleep onset insomnia in children with Attention Deficit Hyperkinesia Disorder  (ADHD) 5
  • Chronic Fatigue Syndrome 6
  • Sleep disturbances in mentally handicapped people 7
  • Smith-Magenis Syndrome 8

References
1.    Lewy AJ, Cutler NL, Sack RL. The endogenous melatonin profile as a marker for circadian phase position. J.Biol.Rhythms 1999;14:227-36.
2.    Arendt J. Biochemistry of the pineal gland. In: Arendt J, ed. Melatonin and the mammalian pineal gland. Cambridge: University Press 1995: 27-63.
3.    Smits MG, Nagtegaal JE, van der Heijden J, Coenen AM, Kerkhof GA. Melatonin for chronic sleep onset insomnia in children: a randomized placebo-controlled trial. J.Child Neurol. 2001;16:86-92.
4.    Smits MG, van Stel HF, van der HK, Meijer AM, Coenen AM, Kerkhof GA. Melatonin improves health status and sleep in children with idiopathic chronic sleep-onset insomnia: a randomized placebo-controlled trial. J.Am.Acad.Child Adolesc.Psychiatry 2003;42:1286-93.
5.    Van der Heijden KB, Smits MG, Someren EJ, Boudewijn GW. Idiopathic chronic sleep onset insomnia in attention-deficit/hyperactivity disorder: a circadian rhythm sleep disorder. Chronobiol.Int.  2005;22:559-70.
6.    Heukelom RO, Prins JB, Smits MG, Bleijenberg G. Influence of melatonin on fatigue severity in patients with chronic fatigue syndrome and late melatonin secretion. Eur.J.Neurol. 2006;13:55-60.
7.    Didden R, Braam W, Smits MG, Curfs LM. Treatment of sleep problems in individuals with Angelman Syndrome: a study of six cases. Sleep-wake research in The Netherlands 2004;15:35-8.
8.    De Leersnyder H, De Blois MC, Claustrat B, Romana S, Albrecht U, Kleist-Retzow JC, Delobel B, Viot G, Lyonnet S, Vekemans M, Munnich A. Inversion of the circadian rhythm of melatonin in the Smith-Magenis syndrome. J.Pediatr. 2001;139:111-6.

This site is edited by M.G.Smits, MD PhD, Director of the centre for Sleep-Wake Disturbances and Chronobiology, Gelderse Vallei Hospital, the Netherlands

Deze website is gemaakt in opdracht van Ziekenhuis Gelderse Vallei. Heeft u vragen, neem dan contact op met dr. M.G. Smits, neuroloog. Polikliniek voor Slaap-Waak Stoornissen en Chronobiologie. E-mail: melatoninecheck@zgv.nl
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