Circadian rhythm sleep disorders in the blind and their treatment with melatonin

doi:10.1016/j.sleep.2006.11.013

Sleep Medicine

Volume 8, Issue 6, September 2007, Pages 651-655

https://doi.org/10.1016/j.sleep.2006.11.013 Get rights and content

Abstract

People who are blind, in addition to having to cope with partial or no sight, have an added handicap; the transmission of ocular light from the retina to their circadian clock is impaired. At its worse, for example in people with both eyes enucleated, this lesion results in desynchronisation of the biological clock (located in the hypothalamic suprachiasmatic nuclei) from the 24 h day/night environment. While in a desynchronised state, symptoms akin to jet lag are experienced (e.g., daytime sleepiness, poor night sleep, reduced alertness and performance during waking). This is a lifelong condition. Daily administration of exogenous melatonin is the current treatment of choice for this so-called “non-24 h sleep/wake disorder”. Melatonin has been shown to correct the underlying circadian rhythm abnormality as well as improve sleep and reduce daytime napping. The effectiveness of melatonin therapy depends upon its time of administration relative to the timing of the person’s circadian clock. If practicable, assessment of an individual’s circadian phase (by measurement of the endogenous melatonin rhythm in plasma, saliva or urine) is recommended prior to commencing treatment to optimise melatonin’s effectiveness.

Introduction

In addition to visual impairment, ocular disease also impairs the transmission of light from the retina to the circadian clock, located in the suprachiasmatic nuclei (SCN) of the hypothalamus. In sighted people, light interacting with the opsin photopigments of the photoreceptor cells (rods and cones) and melanopsin in the photosensitive ganglion cells [1] transmits photic information primarily by means of the retinohypothalamic tract (RHT) to the SCN [2]. One of the roles of light and this “non-visual” pathway is the daily adjustment (resetting) of the circadian timing system so that the circadian clock and its output circadian rhythms remain synchronised (entrained) to the 24 h day created by the earth’s rotation [3], [4], [5]. Synchronisation serves to optimise the timing of the body’s physiology and behaviour with the environment: correct internal and external phase relationships are essential for optimal function [6], [7].

Section snippets

Photic and nonphotic entrainment

Ocular light is the major time cue (zeitgeber) responsible for synchronising the human circadian timing system. Although early work suggested that “nonphotic” time cues such as meals, caffeine, exercise, and sleep–wake cycle were important synchronisers of the human circadian clock [8], today light is considered the primary time cue [3]. In addition to studies in sighted subjects, strong evidence to support this view has come from detailed studies of totally blind people. The demonstration

Circadian rhythms in the blind

Disturbances of circadian rhythms in the blind have been extensively reported in the literature. Following several case reports [9], [14], [15], [16], Lewy and Newsome [17] defined different melatonin rhythms in their study cohort, some of whom were normally entrained (NE), some who were abnormally entrained (AE), some who had no distinct rhythm and some who had free-running rhythms (FR). Later we showed that these types of circadian rhythm patterns (NE, AE or FR) were related to an

Sleep disorders in the blind

Early studies reported a high incidence of sleep disorders in blind people [19], [20]. Whether this was related to specific visual diseases or loss of light perception had not been addressed. An epidemiological study of 388 blind subjects conducted by ourselves [21] showed a higher prevalence and more severe sleep disturbances in those with no light perception (NPL) than in those with some degree of light perception. However, there was no relationship between sleep disturbance (as assessed by

Treatment

The studies described above show a clear relationship between light perception, the type of circadian rhythm abnormality and sleep/wake disturbances.

Appropriately timed, exogenous melatonin has been shown to advance or, more controversially, delay the timing of the circadian clock [25], [26]. Melatonin’s phase shifting effect presumably occurs by means of receptors in the SCN (not MT1 [27], possibly MT2 [28]), although this has yet to be definitively proven. In recent years, this phase shifting

Clinical practice and the future

Recognition of disturbed circadian rhythms in the visually impaired by the clinician is important for the appropriate treatment and management of the sleep disorder. The use of traditional sleep medication (e.g., benzodiazepines, sedative hypnotics) has reportedly brought little benefit to blind people suffering from a circadian rhythm sleep disorder (Lockley, Hack, Skene and Arendt, unpublished data).

The use of melatonin has demonstrable benefits not only in correcting the underlying circadian

Acknowledgements

The authors wish to acknowledge the contribution of their colleagues at the University of Surrey (Drs. Lisa Hack and Steven W. Lockley) and at the Moorfields Eye Hospital (Dr. Homayoun Tabandeh and Prof Alan Bird). The financial support of South Thames Regional Health Authority, Servier R and D, The Wellcome Trust (Grant 048197/Z/96/Z) and Stockgrand Ltd. is gratefully acknowledged.

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View full text

Circadian rhythm sleep disorders in the blind and their treatment with melatonin

Abstract

Introduction

Section snippets

Photic and nonphotic entrainment

Circadian rhythms in the blind

Sleep disorders in the blind

Treatment

Clinical practice and the future

Acknowledgements

Lancet

Lancet

Lancet

Lancet

Am J Ophthalmol

Lancet

Neuron

Neurosci Lett

Neurosci Lett

Brain Res

Brain Res

Phototransduction by retinal ganglion cells that set the circadian clock

Science

Suprachiasmatic nucleus. The minds clock

The effect of light on the human circadian pacemaker

Ciba Found Symp

Circadian rhythm abnormalities in totally blind people: incidence and clinical significance

J Clin Endocrinol Metab

Relationship between melatonin rhythms and visual loss in the blind

J Clin Endocrinol Metab

Chronobiology: Biological timekeeping

Human circadian rhythms in continuous darkness: entrainment by social cues

Science

Free-running circadian rhythms in the blind and their correction by melatonin treatment

Nonphotic entrainment in humans?

J Biol Rhythms

Relative coordination to unknown “weak zeitgebers” in free-running blind individuals

J Biol Rhythms

Nonphotic entrainment of the human circadian pacemaker

Am J Physiol

Blind man living in normal society has circadian rhythms of 24.9 h

Science

Free-running circadian plasma cortisol rhythm in a blind human subject

Clin Endocrinol (Oxf)

Different types of melatonin circadian secretory rhythms in some blind subjects

J Clin Endocrinol Metab