Melanopsin-dependent phototransduction is impaired in delayed sleep–wake phase disorder and sighted non–24-hour sleep–wake rhythm disorder

Abstract

Abstract Study Objectives The circadian system must perform daily adjustments to align sleep–wake and other physiologic rhythms with the environmental light–dark cycle: This is mediated primarily through melanopsin containing intrinsically photosensitive retinal ganglion cells. Individuals with delayed sleep–wake phase disorder (DSWPD) exhibit a delay in sleep–wake timing relative to the average population, while those with sighted non–24-hour sleep–wake rhythm disorder (N24SWD) exhibit progressive delays. An inability to maintain appropriate entrainment is a characteristic of both disorders. In this study, we test the hypothesis that individuals with DSWPD exhibit alteration in melanopsin-dependent retinal photo-transduction as measured with the postillumination pupil response (PIPR). Methods Twenty-one control and 29 participants with DSWPD were recruited from the community and clinic. Of the 29 DSWPD participants, 17 reported a history of N24SWD. A pupillometer was used to measure the PIPR in response to a bright 30-second blue or red-light stimulus. The PIPR was calculated as the difference in average pupil diameter at baseline and 10–40 seconds after light stimulus offset. Results The PIPR was significantly reduced in the DSWPD group when compared with the control group (1.26 ± 1.11 mm vs 2.05 ± 1.04 mm, p < 0.05, t-test). The PIPR was significantly reduced in the sighted N24SWD subgroup when compared with individuals with the history of only DSWPD (0.88 ± 0.58 mm vs 1.82 ± 1.44 mm, p < 0.05, analysis of variance [ANOVA]) or controls (0.88 ± 0.58 mm vs 2.05 ± 1.04 mm, p < 0.01, ANOVA). Conclusions These results indicate that reduced melanopsin-dependent retinal photo-transduction may be a novel mechanism involved in the development of DSWPD and sighted N24SWD.