Original ArticleAntidepressant action of melatonin in the treatment of Delayed Sleep Phase Syndrome
Introduction
Depression is often associated with circadian rhythm abnormalities, and many diverse rhythms such as hormone secretion, neurotransmitter secretion and synthesis and behavioral rhythms can be disrupted in depressed patients, suggesting that such disturbances are not unique to a specific rhythm, but instead involve the central circadian pacemaker which regulates the various rhythms [1]. One rhythm that is often disrupted in depression is the sleep-wake cycle, a disruption that, in turn, might lead to other rhythm disturbances [2], [3].
Delayed Sleep Phase Syndrome (DSPS) falls under the group of intrinsic Circadian Rhythm Sleep Disorders (CRSD), amongst which DSPS is most common both in general and clinical populations [4], [5]. DSPS is characterized by the inability to fall asleep and to awake at conventional times. Sleep onset is usually well past midnight, and sleep offset time is typically past noon [5], [6], [7]. When individuals with DSPS are made to conform to earlier retiring times this leads to marked sleep onset insomnia [6], [8], [9], [10]. DSPS often exhibits psychiatric comorbidities including psychological and functional difficulties such as personality disorders and depression [7], [11], [12]. DSPS patients may show marked nervousness and lack of control of emotional expression [13]. These characteristics may worsen social withdrawal, causing a loss of social cues in synchronizing their circadian rhythm and a further exacerbation of the circadian problem.
The neurohormone melatonin regulates the timing of the central circadian pacemaker located in the Suprachiasmatic Nuclei (SCN) [14], [15], [16]. Significant alterations in melatonin secretion in depressed patients during the acute phase of illness have been documented [17], [18], [19], [20], [21]. Stemming from this observation, several strategies have been utilized to manipulate circadian rhythm to alleviate depression [17], [22], [23], [24], [25], [26]. Exogenous melatonin can modulate the timing of the major sleep-wake episode and have beneficial effects on mood [17], [27]. The aim of this study was to investigate the role of exogenous melatonin treatment as a chronobiotic in ameliorating depressive symptomatology in DSPS patients. In addition, we evaluated urinary sulphatoxymelatonin (aMT6s) as a marker of circadian phase and the effects of melatonin on sleep in DSPS patients.
Section snippets
Study population
Thirteen males aged 35.6 ± 14.0 years and seven females aged 30.8 ± 12.4 years with an established diagnosis of DSPS participated in the study. The following exclusion criteria were applied: shift work, presence of other sleep disorders, age under 16 years, alcohol or drug abuse, current use of psychotropic medications or any other form of medication affecting melatonin secretion, active behavioral treatment, and severe psychiatric and neurological disorders. Prior to inclusion in the study
Melatonin treatment on depression in DSPS
Group I (DSPS patients with comorbid depressive symptoms; n = 8) included three women and five men (mean age: 31.5 ± 7.2 years). Group II (DSPS patients without comorbid depressive symptoms n = 12) included four women and eight men (mean age: 36.2 ± 15.7 years). The mean scores on the CES-D and HDRS-17 were significantly higher in Group I (33.5 ± 9.4 and 13.2 ± 3.6) than in Group II (13.3 ± 3.6 and 5.6 ± 2.4). While at baseline both scales indicated depression in Group I, after melatonin treatment there was a
Discussion
Numerous studies have linked disruptions in the sleep-wake cycle and fundamental circadian dysfunctions to affective illnesses [1], [13], [27], [33], [34], [35], [36]; however, to the best of our knowledge, this study is the first to demonstrate that exogenous melatonin treatment in individuals with endogenous circadian rhythm disruption significantly ameliorates depressive symptomatology. In our sample of 20 DSPS patients 8 individuals had comorbid depressive symptomatology, and even though
Disclosure statement
The authors have nothing to disclose.
Acknowledgement
This study was supported by a research grant from Physicians’ Services Foundation Inc., Canada, No 25/97.
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