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

Abstract

Objective: 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.

Results: 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 PPTlog (partial η2=0.531, P=0.001). However, it was positively correlated with depressive symptoms (partial η2=0.317, P=0.01); PQSI (partial η2=0.306, P=0.017), and NTPs (partial η2=0.23, P=0.04).

Conclusion: 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.

Keywords: 6 sulfatoxymelatonin (aMT6s); depression; fibromyalgia; melatonin; pain.

Figure 1

(A) The measurement of 6-sulfatoxymelatonin (aMT6s) urinary 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). (B) The flow of the study with the inclusion and exclusion criteria of the three groups: depressive patients, fibromyalgia, and healthy subjects. (C) Assessments of fibromyalgia symptoms (pain symptoms, sleep quality, number of trigger points and pain threshold) to correlate with aMT6s urinary secretion across daytime.

Figure 2

6-Sulfatoxymelatonin time points (aMT6s): 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) among FM, MDD, and healthy controls. Notes: Data are presented as mean and the error bars indicate SEM. The asterisk (^*) indicates differences between both groups FM, MDD compared to controls. ^**Indicates difference of MDD compared to controls. All comparisons were performed by a GEE, followed by the Bonferroni test for post hoc multiple comparisons. Abbreviations: FM, fibromyalgia; GEE, generalized estimating equation; HC, healthy control; MDD, major depression disorder SEM, standard error of the mean.