Abstract

Abstract Introduction The post-illumination pupil response (PIPR) is a measure of the responsivity of intrinsically photosensitive retinal ganglion cells (ipRGCs), and reflects the cell biology of the photoentrainment pathway projecting from the retina to the circadian clock. Adequate signaling from the ipRGCs in the retina to the circadian clock is necessary to result in robust circadian output which we hypothesize would increase inter-daily stability (IS), a non-parametric modeling technique that examines stability of rest activity rhythms across successive days. Methods Participants were aged 18–66 years and recruited from the greater Pittsburgh area during the Winter with Seasonal Affective Disorder who completed both actigraphy and pupillometry (n = 16). PIPR measures were collected after a 1 second red or blue light pulse, and are calculated as the Net difference between red and blue at multiple time frames: at 6 seconds post stimulus (PIPR 6), from 10–30 seconds post-stimulus (PIPR 20), or from 10–40 seconds post-stimulus (PIPR 30). Using actigraphy, inter-daily stability (IS) was calculated as the amount of overall variability in the recording that is accounted for by the typical 24-hour profile, and reflects stability of the mean 24-h profile day-to-day. Results Inter-daily stability (IS) was associated with Net PIPR 20 (Β = 0.561; p = .031) and Net PIPR 30 (Β = 0.551; p = .034; all Β’s are standardized), but not Net PIPR 6 (Β = 0.298; p = .304). Retinal irradiance was calculated for each participant based on age and pupil diameter, to account for age-related differences in transmission of the stimulus to the retina. All raw Net PIPR values were adjusted for calculated retinal irradiance, and gender and time since wake were included as covariates. Conclusion Inter-daily stability (IS) values indicate greater stability of 24-hour activity profiles across days. If reduced responsivity to entraining pulses of light is associated with day-to-day instability in activity rhythms, as shown here, we might expect that amplifying entraining light through environmental changes or bright light therapy would normalize inter-daily stability in SAD, or the reverse, stabilizing activity profiles across days could improve depression and/or normalize retinal ipRGC responsivity. Support NIMH K.A.R. MH103303

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