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      Melatonin is a biomarker of circadian dysregulation and is correlated with major depression and fibromyalgia symptom severity

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          This study compared urinary 6-sulfatoxymelatonin (aMT6s) over 24 hours among fibromyalgia (FM), major depression disorder (MDD), and healthy control (HC) groups, and examined whether rhythm is correlated with depressive symptoms. To answer this question we compared the rhythm of urinary aMT6s secretion among each group in four time series: morning (06:00–12:00 hours), afternoon (12:00–18:00 hours), evening (18:00–24:00 hours), and night (24:00–06:00 hours). In the FM subjects, we assessed if the rhythm of urinary aMT6s secretion is associated with pain severity, sleep quality, number of trigger points (NTPs), and the pain pressure threshold (PPT).

          Patients and methods

          We included 54 women, aged 18–60 years with diagnosis of FM (n=18), MDD (n=19), and HC (n =17). The 24-hour urinary aMT6s was evaluated according to four standardized periods. The assessment instruments were the Hamilton Depression Rating Scale (HDRS), Pittsburgh Sleep Quality Index, and Fibromyalgia Impact Questionnaire.


          A generalized estimating equation revealed no difference in the daily load of aMT6s secretion among the three groups ( P=0.49). However, at the daily time (06:00–18:00 hours), the load secretion of aMT6s reached 41.54% and 60.71% in the FM and MDD, respectively, as compared to 20.73% in the HC ( P<0.05). A higher score in the HDRS was positively correlated with the amount of aMT6s secretion during daytime (06:00–18:00 hours). Also, multivariate linear regression revealed that in FM subjects, the aMT6s secretion during daytime (06:00–18:00 hours) was negatively correlated with the PPT log (partial η 2=0.531, P=0.001). However, it was positively correlated with depressive symptoms (partial η 2=0.317, P=0.01); PQSI (partial η 2=0.306, P=0.017), and NTPs (partial η 2=0.23, P=0.04).


          A more significant load of aMT6s secretion during daytime hours was observed in MDD and FM subjects compared to HC. These findings help to comprehend the biological basis of these disorders and show how disruption in melatonin secretion is positively correlated with clinical symptoms.

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          Most cited references 35

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          Extrapineal melatonin: sources, regulation, and potential functions.

          Endogenous melatonin is synthesized from tryptophan via 5-hydroxytryptamine. It is considered an indoleamine from a biochemical point of view because the melatonin molecule contains a substituted indolic ring with an amino group. The circadian production of melatonin by the pineal gland explains its chronobiotic influence on organismal activity, including the endocrine and non-endocrine rhythms. Other functions of melatonin, including its antioxidant and anti-inflammatory properties, its genomic effects, and its capacity to modulate mitochondrial homeostasis, are linked to the redox status of cells and tissues. With the aid of specific melatonin antibodies, the presence of melatonin has been detected in multiple extrapineal tissues including the brain, retina, lens, cochlea, Harderian gland, airway epithelium, skin, gastrointestinal tract, liver, kidney, thyroid, pancreas, thymus, spleen, immune system cells, carotid body, reproductive tract, and endothelial cells. In most of these tissues, the melatonin-synthesizing enzymes have been identified. Melatonin is present in essentially all biological fluids including cerebrospinal fluid, saliva, bile, synovial fluid, amniotic fluid, and breast milk. In several of these fluids, melatonin concentrations exceed those in the blood. The importance of the continual availability of melatonin at the cellular level is important for its physiological regulation of cell homeostasis, and may be relevant to its therapeutic applications. Because of this, it is essential to compile information related to its peripheral production and regulation of this ubiquitously acting indoleamine. Thus, this review emphasizes the presence of melatonin in extrapineal organs, tissues, and fluids of mammals including humans.
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            Comorbidity of chronic insomnia with medical problems.

            Determine the comorbidity of insomnia with medical problems. Cross-sectional and retrospective. Community-based population of 772 men and women, aged 20 to 98 years old. Self-report measures of sleep, health, depression, and anxiety. People with chronic insomnia reported more of the following than did people without insomnia: heart disease (21.9% vs 9.5%), high blood pressure (43.1% vs 18.7%), neurologic disease (7.3% vs 1.2%), breathing problems (24.8% vs 5.7%), urinary problems (19.7% vs 9.5%), chronic pain (50.4% vs 18.2%), and gastrointestinal problems (33.6% vs 9.2%). Conversely, people with the following medical problems reported more chronic insomnia than did those without those medical problems: heart disease (44.1% vs 22.8%), cancer (41.4% vs 24.6%), high blood pressure (44.0% vs 19.3%), neurologic disease (66.7% vs 24.3%), breathing problems (59.6% vs 21.4%), urinary problems (41.5% vs 23.3%), chronic pain (48.6% vs 17.2%), and gastrointestinal problems (55.4% vs 20.0%). When all medical problems were considered together, only patients with high blood pressure, breathing problems, urinary problems, chronic pain, and gastrointestinal problems continued to have statistically higher levels of insomnia than those without these medical disorders. This study demonstrates significant overlap between insomnia and multiple medical problems. Some research has shown it is possible to treat insomnia that is comorbid with select psychiatric (depression) and medical (eg, pain and cancer) disorders, which in turn increases the quality of life and functioning of these patients. The efficacy of treating insomnia in many of the above comorbid disorders has not been tested, indicating a need for future treatment research.
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              Neurobiology of depression: an integrated view of key findings

              Aims The objectives of the present review were to summarise the key findings from the clinical literature regarding the neurobiology of major depressive disorder (MDD) and their implications for maximising treatment outcomes. Several neuroanatomical structures in the prefrontal and limbic areas of the brain are involved in affective regulation. In patients with MDD, alterations in the dynamic patterns of activity among these structures have profound implications for the pathogenesis of this illness. Discussion The present work reviews the evidence for the progressive nature of MDD along with associated changes in neuroanatomical structure and function, especially for the hippocampus. The role of glucocorticoids, inflammatory cytokines and brain-derived growth factors are discussed as mediators of these pathological alterations. From this integrated model, the role of antidepressant therapy in restoring normative processes is examined along with additional treatment guidelines. Conclusion Major depressive disorder is an illness with significant neurobiological consequences involving structural, functional and molecular alterations in several areas of the brain. Antidepressant pharmacotherapy is associated with restoration of the underlying physiology. Clinicians are advised to intervene with MDD using an early, comprehensive treatment approach that has remission as the goal.

                Author and article information

                J Pain Res
                J Pain Res
                Journal of Pain Research
                Journal of Pain Research
                Dove Medical Press
                31 January 2019
                : 12
                : 545-556
                [1 ]School of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil, wcaumo@ 123456hcpa.edu.br
                [2 ]Pain and Palliative Care Service at Hospital de Clínicas de Porto Alegre (HCPA), Laboratory of Pain and Neuromodulation at UFRGS, Porto Alegre, Brazil, wcaumo@ 123456hcpa.edu.br
                [3 ]Pain and Anesthesia in Surgery Department, School of Medicine, UFRGS, Porto Alegre, Brazil, wcaumo@ 123456hcpa.edu.br
                [4 ]Psychiatry Department, School of Medicine, UFRGS, Porto Alegre, Brazil
                [5 ]Laboratorio de Cronobiologia e Sono do Hospital de Clinicas de Porto Alegre; Porto Alegre, Brazil
                [6 ]Postgraduate Program in Health and Human Development, La Salle Universitary Center, Canoas, Brazil
                [7 ]Pharmacology Department, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, Brazil
                [8 ]Centro de Ciências da Saúde – Departamento de Nutrição da Universidade Federal De Santa Catarina, Florianopolis, Brazil
                Author notes
                Correspondence: Wolnei Caumo, Laboratory of Pain and Neuromodulation, School of Medicine at UFRGS, Hospital de Clínicas de Porto Alegre, Street Ramiro Barcelos, Porto Alegre, RS, 90035-003, Brazil, Email wcaumo@ 123456hcpa.edu.br
                © 2019 Caumo et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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