Dysregulation of melatonin rhythm in Parkinson's and Huntington's disease: a systematic review and meta-analysis.

Background: Parkinson's disease (PD) and Huntington's disease (HD) are progressive neurodegenerative diseases with early non-motor symptoms, such as sleep disturbances, which often precede motor symptoms but are frequently overlooked. Although HD can be diagnosed genetically, PD lacks reliable biomarkers for its early detection. Melatonin, a circadian regulator, may be a promising early biomarker to address this issue. Methods: A database search was performed to identify relevant studies. Meta-analyses were conducted using the ratio of means (RoM) as an effect size and I2 as a heterogeneity test. Results: Melatonin rhythmicity was significantly disrupted in both PD and HD groups. PD patients showed reduced amplitude [RoM = 0.76, 95% CI (0.26 to 1.26); p = 0.00] and increased 24-h area under the curve (AUC) [RoM = 1.06, 95% CI (0.26 to 1.85); p = 0.01]. In manifest HD, both amplitude [RoM = 0.92, 95% CI (0.81 to 1.02); p = 0.00] and acrophase [RoM = 0.92, 95% CI (0.07 to 1.78); p = 0.03] significantly decreased. PD patients with sleep disorders had significantly higher melatonin concentrations than the non-sleep disorder group, with a significant test group difference of p = 0.00. HD patients showed a stage-wise decline. Conclusion: This study suggests that melatonin could serve as a biomarker for the early diagnosis of PD and to track the progression of HD, thus complementing existing diagnostic tools. Systematic review registration: CRD42024544116, https://www.crd.york.ac.uk/PROSPERO/view/CRD42024544116.