Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/128548
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Type: Journal article
Title: A PERIOD3 variable-number-tandem-repeat polymorphism modulates melatonin treatment response in Delayed Sleep-Wake Phase Disorder
Author: Magee, M.
Sletten, T.L.
Murray, J.M.
Gordon, C.J.
Lovato, N.
Bartlett, D.J.
Kennaway, D.J.
Lockley, S.W.
Lack, L.C.
Grunstein, R.R.
Archer, S.N.
Rajaratnam, S.M.
Delayed Sleep on Melatonin (DelSoM) Study Group
Citation: Journal of Pineal Research, 2020; 69(4):e12684-1-e12684-13
Publisher: Wiley
Issue Date: 2020
ISSN: 0742-3098
1600-079X
Statement of
Responsibility: 
Michelle Magee, Tracey L. Sletten, Jade M. Murray, Christopher J. Gordon, Nicole Lovato, Delwyn J. Bartlett, David J. Kennaway, Steven W. Lockley, Leon C. Lack, Ronald R. Grunstein, Simon N. Archer, Shantha M.W. Rajaratnam, Delayed Sleep on Melatonin, DelSoM, Study Group
Abstract: We examined whether a polymorphism of the PERIOD3 gene (PER3; rs57875989) modulated the sleep promoting effects of melatonin in Delayed Sleep-Wake Phase Disorder (DSWPD). One hundred and four individuals (53 males; 29.4±10.0 years) with DSWPD and a delayed dim light melatonin onset (DLMO) collected buccal swabs for genotyping (PER3(4/4) n=43; PER3 5 allele [heterozygous and homozygous] n=60). Participants were randomised to placebo or 0.5mg melatonin taken 1 hour before desired bedtime (or ~ 1.45 h before DLMO), with sleep attempted at desired bedtime (4 weeks; 5-7 nights/week). We assessed sleep (diary and actigraphy), Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Patient-Reported Outcomes Measurement Information System (PROMIS: Sleep Disturbance, Sleep-Related Impairment), Sheehan Disability Scale (SDS), and Patient- and Clinician-Global Improvement (PGI-C, CGI-C). Melatonin treatment response on actigraphic sleep onset time did not differ between genotypes. For PER3(4/4) carriers, self-reported sleep onset time was advanced by a larger amount and sleep onset latency (SOL) was shorter in melatonin-treated patients compared to those receiving placebo (P=0.008), while actigraphic sleep efficiency in the first third of the sleep episode (SE T1) did not differ. For PER3 5 carriers, actigraphic SOL and SE T1 showed a larger improvement with melatonin (P<0.001). Melatonin improved ISI (P=0.005), PROMIS Sleep Disturbance (P<0.001) and Sleep-Related Impairment (P=0.017), SDS (P=0.019), PGI-C (P=0.028), and CGI-C (P=0.016) in PER3(4/4) individuals only. Melatonin did not advance circadian phase. Overall, PER3(4/4) DSWPD patients have a greater response to melatonin treatment. PER3 genotyping may therefore improve DSWPD patient outcomes.
Keywords: Circadian rhythm sleep disorders; Delayed Sleep-Wake Phase Disorder; melatonin; PERIOD3; polymorphism; variable number tandem repeat
Rights: © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
DOI: 10.1111/jpi.12684
Grant ID: http://purl.org/au-research/grants/nhmrc/1031513
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