Hypothalamic volume loss is associated with reduced melatonin output in Parkinson's disease
Breen, David P
Burn, David J
Brooks, David J
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Breen, D. P., Nombela, C., Vuono, R., Jones, S., Fisher, K., Burn, D. J., Brooks, D. J., et al. (2016). Hypothalamic volume loss is associated with reduced melatonin output in Parkinson's disease. Movement Disorders, 31 1062-1066. https://doi.org/10.1002/mds.26592
Background Recent studies have suggested that melatonin—a hormone produced by the pineal gland under circadian control—contributes to PD-related sleep dysfunction. We hypothesized that degenerative changes to the neural structures controlling pineal function (especially the suprachiasmatic nuclei of the anterior hypothalamus) may be responsible for reduced melatonin output in these patients. We compared hypothalamic volumes in PD patients with matched controls and determined whether volume loss correlated with reduced melatonin output in the PD group. Methods A total of 12 PD patients and 12 matched controls underwent magnetic resonance imaging to determine hypothalamic volume. In addition, PD patients underwent 24-hour blood sampling in a controlled environment to determine serum melatonin concentrations using enzyme-linked immunosorbent assays. Results PD patients had significantly reduced hypothalamic gray matter volume when compared with matched controls. Melatonin levels were significantly associated with hypothalamic gray matter volume and disease severity in PD patients. Conclusion Melatonin levels are associated with hypothalamic gray matter volume loss and disease severity in PD patients. This provides anatomical and physiological support for an intrinsic sleep and circadian phenotype in PD.
The authors would like to acknowledge the study funders: the Big Lottery Fund (C498A738) and Parkinson’s UK (J-0802). The research was supported by a National Institute of Health Research Biomedical Research Award (to Addenbrooke’s Hospital/University of Cambridge), the Wellcome Trust (103838, 100333/Z/12/Z) and a Raymond and Beverly Sackler Studentship (to DPB). We would like to thank staff at the Wellcome Trust Clinical Research Facility in Addenbrooke’s Hospital, Cambridge for performing the melatonin blood sampling.
WELLCOME TRUST (103838/Z/14/Z)
Wellcome Trust (100333/Z/12/Z)
Medical Research Council (MC_U105597119)
Wellcome Trust (093875/Z/10/Z)
External DOI: https://doi.org/10.1002/mds.26592
This record's URL: https://www.repository.cam.ac.uk/handle/1810/253668