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Daytime Salivary Melatonin Related to Gastrointestinal Symptoms in Young Adults Seeking Psychiatric Care
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 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 Univ, Uppsala, Sweden..
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2018 (English)In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 83, no 9, p. S185-S186Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
2018. Vol. 83, no 9, p. S185-S186
Keywords [en]
Melatonin, Irritable Bowel Syndrome, Depression
National Category
Psychiatry Gastroenterology and Hepatology
Identifiers
URN: urn:nbn:se:uu:diva-361431ISI: 000432466300462OAI: oai:DiVA.org:uu-361431DiVA, id: diva2:1269421
Conference
73rd Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry (SOBP), 2018, New York, NY
Available from: 2018-12-10 Created: 2018-12-10 Last updated: 2019-11-18Bibliographically 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
2. Melatonin in the gastrointestinal tract
Open this publication in new window or tab >>Melatonin in the gastrointestinal tract
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Melatonin is recognised as the pineal hormone regulating sleep and circadian rhythm. It has also been identified in peripheral tissues (mainly in animals) and thought to display a variety of actions, including anti-inflammatory properties, regulation of gastrointestinal (GI) functions, glucose homeostasis and beneficial effects in different tumour types. Patients with irritable bowel disorder commonly exhibit psychiatric co-morbidity and disturbances of the gut-brain axis have been proposed to play a role in these disorders. The focus of this thesis was to study melatonin and melatonin receptors in the normal human GI tract, the pancreas and small intestinal neuroendocrine tumours. The thesis also explores the complex relationship between GI symptoms and underlying psychiatric traits in the context of elevated levels of peripheral melatonin during waking hours.

In paper I-II, tissue samples from the normal human GI tract and pancreas and tumour tissue from small intestinal neuroendocrine tumours were analysed for expression of melatonin and melatonin receptors using immunohistochemistry. For tumour patients, melatonin was also analysed in plasma and set in relation to symptoms and outcome. In paper III-IV, a cohort of young adults (18-25 years) seeking psychiatric care was examined for GI symptoms, melatonin levels in saliva, depressive symptoms and anxiety traits. Psychiatric assessments were performed using structured or semi structured interviews. Depressive symptoms were measured using the self-rating version of the Montgomery-Åsberg Depression Rating Scale; GI symptoms were measured using the Gastrointestinal Symptoms Rating Scale for Irritable Bowel Syndrome; and personality traits were evaluated using the Swedish Universities Scales of Personality.

Melatonin and melatonin receptors were widely expressed in the normal human gut and pancreas (paper I) but even in small intestinal neuroendocrine tumours known to produce serotonin (paper II). The intensity of the melatonin immunoreactivity in tumour tissue was found to correlate with lower proliferation index. After treatment, plasma levels of melatonin were reduced in tumour patients. Young adult patients seeking psychiatric care reported more GI symptoms than healthy controls, regardless of the currently active psychotropic medication. The level of GI symptoms was associated with severity of depressive symptoms and trait anxiety (paper III). Higher postprandial levels of melatonin were associated with the GI symptoms of bloating and pain (paper IV).

In summary, these findings demonstrate the widespread presence of melatonin in the human gut and confirm a link between melatonin, psychiatric health and GI symptoms.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2019. p. 63
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1616
Keywords
melatonin, MT1, MT2, gastointestinal tract, small intestinal neuroendocrine tumours, IBS, depression, anxiety, personality and affective disorder
National Category
Psychiatry Endocrinology and Diabetes Gastroenterology and Hepatology Cancer and Oncology
Research subject
Medical Science; Psychiatry
Identifiers
urn:nbn:se:uu:diva-396347 (URN)978-91-513-0814-2 (ISBN)
Public defence
2020-01-17, Humanistiska teatern, Thunbergsvägen 3, Uppsala, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2019-12-18 Created: 2019-11-18 Last updated: 2020-01-13

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Söderquist, FannySundberg, IsakRamklint, MiaHellström, Per M.Cunningham, Janet

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