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Salivary Melatonin in Relation to Depressive Symptom Severity in Young Adults.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.ORCID iD: 0000-0003-3271-0456
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
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2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 4, article id e0152814Article in journal (Refereed) Published
Abstract [en]

Reduced levels of melatonin have been associated with severe depression. The aim was to investigate the correlation between salivary melatonin and dimensional measures of depressive symptom severity in young adult psychiatric patients. Levels of melatonin were analyzed in six saliva samples during waking hours from 119 young adult patients under outpatient psychiatric care. Melatonin levels were tested for association with the severity of depressive symptoms using the self-rating version of the Montgomery Åsberg Depression Rating Scale (MADRS-S). Where possible, depressive symptoms were assessed again after 6±2 months of treatment. Response was defined as decrease in MADRS-S by ≥50% between baseline and follow-up. Patients with levels of melatonin in the lowest quartile at bedtime had an increased probability of a high MADRS-S score compared to those with the highest levels of melatonin (odds ratio 1.39, 95% CI 1.15-1.69, p<0.01). A post hoc regression analysis found that bedtime melatonin levels predicted response (odds ratio 4.4, 95% CI 1.06-18.43, p<0.05). A negative relationship between salivary melatonin and dimensional measures of depressive symptom severity was found in young patients under outpatient psychiatric care. Bedtime salivary melatonin levels may have prognostic implications.

Place, publisher, year, edition, pages
2016. Vol. 11, no 4, article id e0152814
Keywords [en]
Melatonin, Depression, Depressive Symptoms, Saliva, Severity, Prognosis, MADRS-S, Sheehan Disability Scale, HbA1C, Oxi-LDL, Research Domain Criteria (RDoC)
National Category
Psychiatry Neurosciences
Research subject
Psychiatry
Identifiers
URN: urn:nbn:se:uu:diva-291425DOI: 10.1371/journal.pone.0152814ISI: 000373592100035PubMedID: 27042858OAI: oai:DiVA.org:uu-291425DiVA, id: diva2:925531
Projects
Uppsala Psykiatriska Provsamling
Funder
Swedish Society of MedicineAvailable from: 2016-05-02 Created: 2016-05-02 Last updated: 2018-12-12Bibliographically approved
In thesis
1. Exploring Links between Melatonin, Inflammation and Depression
Open this publication in new window or tab >>Exploring Links between Melatonin, Inflammation and Depression
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Major depressive disorder (MDD) is one of the leading global causes of disease burden. Worse yet, about one third of the patients with MDD do not experience a remission with current treatments. The symptoms of MDD likely represent a variety of underlying pathologic processes and more knowledge about these processes is needed to optimize treatment for MDD. The focus of this thesis was to study the relationship between inflammation, melatonin and symptoms of depression. 

In papers I-III a population of young adults seeking psychiatric care was examined for depressive symptoms, melatonin levels in saliva, gastrointestinal (GI) symptoms and inflammatory markers in blood. In paper IV a cohort of patients with hepatitis C receiving treatment with new direct-acting agents (DAAs) were prospectively followed during treatment for depressive symptoms and sleep.

All patients were diagnosed by means of structured or semi-structured interviews and depressive symptoms were assessed with the self-rating version of the Montgomery Åsberg Depression Rating Scale. Sleep quality was measured by the Pittsburgh Sleep Quality Index, and GI symptoms were assessed with the Gastrointestinal Symptom Rating Scale-IBS. Melatonin in saliva was measured using enzyme-linked immunosorbent assay, and inflammatory markers in blood were analysed by proximity extension assay.

In young adults seeking psychiatric care melatonin levels at bedtime were inversely correlated with depressive symptoms. In those patients with a current depressive episode low melatonin values at bedtime were a negative prognostic factor for response after 6 months (paper I). Postprandial melatonin levels were positively associated with GI symptoms of bloating and pain (paper II). Postprandial melatonin levels were also associated with the inflammatory markers vascular endothelial growth factor A (VEGF-A), monocyte chemoattractant protein-1 (MCP-1) and monocyte inflammatory protein-1α (MIP-1α). Evening levels of melatonin did not correlate with the inflammatory markers. VEGF-A and MCP-1 as well as postprandial levels of melatonin correlated with a diagnosis of anxiety disorder, whereas MIP-1α correlated with MDD (paper III). Patients with hepatitis C underwent treatment with DAAs without experiencing pronounced psychiatric side effects in terms of depressive symptoms or sleep disturbances (paper IV).

In summary, the findings confirm a relationship between bedtime melatonin levels and depressive symptoms. The findings also show a connection between daytime melatonin and GI-symptoms. In addition, the findings indicate an association between inflammation and daytime melatonin. Together these results demonstrate links between melatonin, inflammation and depression. Lastly, interferon-free treatment against hepatitis C did not induce depressive symptoms.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2019. p. 70
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1526
Keywords
melatonin, inflammation, depression, biomarkers, cytokines, anxiety, hepatitis C
National Category
Psychiatry
Research subject
Psychiatry
Identifiers
urn:nbn:se:uu:diva-369411 (URN)978-91-513-0535-6 (ISBN)
Public defence
2019-02-15, Sal IV, Universitetshuset, Biskopsgatan 3, Uppsala, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2019-01-25 Created: 2018-12-12 Last updated: 2019-02-18

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Sundberg, IsakRamklint, MiaStridsberg, MatsPapadopoulos, Fotios CEkselius, LisaCunningham, Janet L

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