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

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.