Combined cortisol and melatonin measurements with detailed parameter analysis can assess the circadian rhythms in bipolar disorder patients

Objectives Bipolar disorder (BD) is a common chronic mental illness. The circadian clock disorder shows a significant correlation with the pathogenesis, phenotype and recurrence of BD. We aim to evaluate non-invasive methods that can comprehensively assess the circadian rhythmicity in BD patients. Methods We non-invasively collected salivary samples and oral epithelial cells from recruited subjects. Then the levels of cortisol and melatonin in saliva were measured and the circadian clock gene expressions (PER2 and BMAL1) of epithelial cells were analyzed. Due to the disease characteristics of the manic patients who were difficult to cooperate with the protocol, only one patient at manic episode was recruited. Besides, 11 patients at the depressive episode, 15 healthy controls and four patients at recovery stage were recruited. Results Our results exhibited that the peak phase of cortisol level mainly manifested around 8:00 a.m., and the maximal melatonin level reached around 5:00 a.m. The phase of cortisol in patients with depression did not change significantly, but the level of cortisol decreased significantly, while the phase of melatonin level moved forward about 2.5 hr. Furthermore, the levels and phases of cortisol and melatonin in recovery patients tended to be similar to those of healthy controls. Conclusions With detailed parameter analysis, the combined detection of melatonin and cortisol can better judge the biological clock disorder of bipolar patients. The circadian rhythms of patients at the recovery stage tend to be normal. The clock gene expression examination needs strict quality control and more investigations before being applied to assess human circadian rhythms.