Melatonin as a Biomarker of Circadian Dysregulation

Mirick, Dana K.; Davis, Scott

doi:10.1158/1055-9965.epi-08-0605

Cited by 142 publications

(118 citation statements)

References 120 publications

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“…40 Our findings might suggest the potential use of exogenous melatonin treatment of patients with AD to improve sleep efficiency and skin inflammation.…”

Section: Figurementioning

confidence: 74%

Atopic Dermatitis, Melatonin, and Sleep Disturbance

et al. 2014

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WHAT'S KNOWN ON THIS SUBJECT: Sleep disturbance affects 47% to 60% of children with atopic dermatitis and is a leading cause of impaired quality of life for the patients and their family. WHAT THIS STUDY ADDS:Sleep disturbance in children with atopic dermatitis can be predicted by a Scoring Atopic Dermatitis index of $48.7, and lower nocturnal melatonin secretion might play a role in the pathophysiology. abstract BACKGROUND AND OBJECTIVES: Sleep disturbance is common in patients with atopic dermatitis (AD). However, studies have largely been questionnaire-based, and the pathophysiology remains unclear. The aims of this study were to determine objective characteristics of sleep disturbance in children with AD and explore contributing factors and clinical predictors.METHODS: Sleep parameters were measured by actigraphy and polysomnography in 72 patients with AD and 32 controls ages 1 to 18 years. Urinary 6-sulfatoxymelatonin levels, serum cytokines, and total and allergen-specific immunoglobulin E (IgE) levels were also measured. RESULTS:The patients with AD had significantly reduced sleep efficiency, longer sleep onset latency, more sleep fragmentation, and less nonrapid eye movement sleep. Results from actigraphy correlated well with those from polysomnography. The AD disease severity was associated with sleep disturbance (r = 0.5520.7), and a Scoring Atopic Dermatitis index of $48.7 predicted poor sleep efficiency with a sensitivity of 83.3% and a specificity of 75% (area under the curve = 0.81, P = .001). Lower nocturnal melatonin secretion was significantly associated with sleep disturbance in the patients with AD. Other correlates of sleep disturbance included pruritus, scratching movements, higher total serum IgE levels, and allergic sensitization to dust mite and staphylococcal enterotoxins. CONCLUSIONS:Poor sleep efficiency is common in children with AD and can be predicted by the Scoring Atopic Dermatitis index. Melatonin and IgE might play a role in the sleep disturbance. Further studies are required to explore the mechanisms and clinical implications, and actigraphy could serve as a useful evaluating tool. Atopic dermatitis (AD) is a common chronically relapsing pruritic inflammatory skin disease. 1 Disturbed sleep is frequently reported by the patients and their family and is a major factor leading to an impaired quality of life. [2][3][4] Sleep disturbance can have many negative consequences, including impaired neurocognitive function, higher rates of behavioral problems, and changes in mood. 5,6 Therefore, the recognition and proper management of sleep disturbance should be an important issue in AD.The sleep disturbance in AD might be due to the pruritus and scratching movements during sleep, 7-10 but it is likely that other factors are involved. 11 Melatonin is a hormone secreted by the pineal gland that is essential for regulating the circadian rhythm. 12 Dysfunction in the diurnal secretion of melatonin in patients with AD has been reported, 13 but its association with their sleep disturbance has...

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“…40 Our findings might suggest the potential use of exogenous melatonin treatment of patients with AD to improve sleep efficiency and skin inflammation.…”

Section: Figurementioning

confidence: 74%

Atopic Dermatitis, Melatonin, and Sleep Disturbance

et al. 2014

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“…In contrast to our results, Borisenkov et al [6] reported circadian variations in salivary TAC concentrations with maximum at 6.00 a.m. and minimum at 3 p.m. and suggested that the influence of melatonin in the morning increases TAC. Melatonin, an important circadian marker which synchronizes the internal hormonal environment according to the light-dark cycle, has been proved to be an effective antioxidant [31,44]. Melatonin is measurable in saliva and significant correlation was reported between melatonin concentrations in blood and saliva [35].…”

Section: Effect Of Circadian Rhythmmentioning

confidence: 99%

Salivary Markers of Oxidative Stress and Antioxidant Status: Influence of External Factors

2013

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Abstract.BACKGROUND: Salivary markers of oxidative stress and antioxidant status represent promising tool for the research of oral diseases. One of the criteria is the validation of these biomarkers from the perspective of the confounding and modifying factors. AIM: To examine the effect of circadian rhythm, tooth-brushing and ascorbic acid treatment on selected salivary markers of oxidative and carbonyl stress, and antioxidant status. SUBJECTS AND METHODS: Whole unstimulated saliva samples were collected from 19 healthy participants three times during a day, before and after tooth-brushing, and before and after the administration of vitamin C (250 mg). Advanced oxidation protein products (AOPP), thiobarbituric acid reactive substances (TBARS), advanced glycation end products (AGEs), ferric reducing antioxidant power (FRAP) and total antioxidant capacity (TAC) were measured. RESULTS: Salivary AGEs levels varied significantly during the day (p < 0.05) with the highest concentrations in the morning. FRAP levels varied during the day (p < 0.01) with the highest concentrations in the afternoon. Tooth-brushing decreased AGEs (p < 0.05) and TBARS levels (p < 0.01) and increased FRAP levels (p < 0.05). Single intake of vitamin C significantly decreased AGEs (p < 0.001) and increased both FRAP (p < 0.01) and TAC (p < 0.01) concentrations. CONCLUSION: Significant daily variations were observed in salivary AGEs and FRAP levels. Tooth-brushing and treatment with vitamin C decreased carbonyl stress and increased the antioxidant status. These results are important from the perspective of using saliva for the research of oral diseases.

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“…MLT is a leading candidate for mediating the putative ALANinduced circadian disruption at the molecular, hormonal, and epigenetic levels. Therefore, MLT serves as an operational biomarker for circadian disruption and a promising chronobiotic drug target for circadian disruption-related diseases [245]. Enhancement of the circadian amplitude by pharmalogical agents, such as Nobiletin, has been found to ameliorate circadian disruption-related syndromes, such as obesity and metabolic disorders [246].…”

Section: Discussionmentioning

confidence: 99%

Artificial light-at-night – a novel lifestyle risk factor for metabolic disorder and cancer morbidity

Zubidat

Haim

2017

Journal of Basic and Clinical Physiology and Pharmacology

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Both obesity and breast cancer are already recognized worldwide as the most common syndromes in our modern society. Currently, there is accumulating evidence from epidemiological and experimental studies suggesting that these syndromes are closely associated with circadian disruption. It has been suggested that melatonin (MLT) and the circadian clock genes both play an important role in the development of these syndromes. However, we still poorly understand the molecular mechanism underlying the association between circadian disruption and the modern health syndromes. One promising candidate is epigenetic modifications of various genes, including clock genes, circadian-related genes, oncogenes, and metabolic genes. DNA methylation is the most prominent epigenetic signaling tool for gene expression regulation induced by environmental exposures, such as artificial light-at-night (ALAN). In this review, we first provide an overview on the molecular feedback loops that generate the circadian regulation and how circadian disruption by ALAN can impose adverse impacts on public health, particularly metabolic disorders and breast cancer development. We then focus on the relation between ALAN-induced circadian disruption and both global DNA methylation and specific loci methylation in relation to obesity and breast cancer morbidities. DNA hypo-methylation and DNA hyper-methylation, are suggested as the most studied epigenetic tools for the activation and silencing of genes that regulate metabolic and monostatic responses. Finally, we discuss the potential clinical and therapeutic roles of MLT suppression and DNA methylation patterns as novel biomarkers for the early detection of metabolic disorders and breast cancer development.

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Melatonin as a Biomarker of Circadian Dysregulation

Cited by 142 publications

References 120 publications

Atopic Dermatitis, Melatonin, and Sleep Disturbance

Atopic Dermatitis, Melatonin, and Sleep Disturbance

Salivary Markers of Oxidative Stress and Antioxidant Status: Influence of External Factors

Artificial light-at-night – a novel lifestyle risk factor for metabolic disorder and cancer morbidity

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