Exploring Links between Melatonin, Inflammation and Depression

Abstract

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