Endocrine biomarkers related to sleep-wake cycle and sleep disturbances in patients with bipolar disorder: A systematic review

Abstract

Background and objectives

Sleep and circadian disturbances have been widely studied in patients with bipolar disorder. However, there is no clear evidence about the role of peripheral biomarkers of the circadian cycle in this population. This systematic review aims to identify potential endocrine blood biomarkers of circadian rhythms and study their relationship with sleep problems in these patients.

Methods

An electronic search was performed of PubMed and PsycINFO databases. It included articles about the topic from 1991 through 2021. The search strategy was: ("peripheral biomarkers" OR "biological markers" OR biomarker OR cortisol OR melatonin OR orexin OR hypocretin) AND (blood OR serum OR plasma) AND (“sleep-wake” OR "circadian rhythm" OR sleep OR insomnia) AND "bipolar."

Results

After excluding duplicates, 92 records were obtained. Only 5 studies met the inclusion criteria (n=499; bipolar disorder=125; unipolar depression=148; schizophrenia=80; controls=146). The endocrine parameters analyzed were: cortisol (3 studies), melatonin (1 study), and orexin-A (1 study). Overall, no significant associations were detected between these biomarkers and sleep disturbances, assessed with subjective (psychometric evaluation) and/or objective (polysomnography) measures.

Conclusion

This review highlights the lack of studies exploring the role of endocrine biomarkers related to circadian function in the pathophysiology of sleep disturbances in bipolar disorder.