The role of retinal irradiance estimates in melanopsin-driven retinal responsivity: A reanalysis of the post-illumination pupil response (PIPR) in seasonal affective disorder.

To isolate melanopsin contributions to retinal sensitivity measured by the post-illumination pupil response (PIPR), controlling for individual differences in non-melanopsin contributions including retinal irradiance is required. When methodologies to negate such differences present barriers, statistical controls have included age, baseline diameter, iris pigmentation, and circadian time of testing. Alternatively, the pupil light reflex (PLR) and calculations estimating retinal irradiance both reflect retinal irradiance, while the PLR also reflects downstream pathways. We reanalyzed data from an observational, correlational study comparing the PIPR across seasons in seasonal affective disorder (SAD) and controls. The PIPR was measured in 47 adults in Pittsburgh, Pennsylvania (25 SAD) over 50 s after 1 s red and blue stimuli of 15.3 log photons/cm2/s. The PLR was within 1 s while PIPR was averaged over 10-40 seconds post-stimulus. Two raters ranked iris pigmentation using a published scale. We evaluated model fit using Akaike's Information Criterion (AIC) across different covariate sets. The best fitting models included either estimated retinal irradiance or PLR, and circadian time of testing. The PLR is collected contemporaneously in PIPR studies and is an individually specific measure of nonspecific effects, while being minimally burdensome. This work extends the prior publication by introducing theoretically grounded covariates that improved analytic model fits based on AIC specific to the present methods and sample. Such quantitative methods could be helpful in studies which must balance participant and researcher burden against tighter methodological controls of individual differences in retinal irradiance.

Do sleep and circadian characteristics predict alcohol use in adult drinkers?

BACKGROUND: While sleep and circadian rhythms are recognized contributors to the risk for alcohol use and related problems, few studies have examined whether objective sleep and circadian measures can predict future alcohol use in humans, and no such studies have been conducted in adults. This study examined whether any baseline sleep and/or circadian characteristics of otherwise healthy adults predicted their alcohol use over the subsequent 12 months. METHODS: Participants (21-42 years) included 28 light and 50 heavy drinkers. At baseline, a comprehensive range of self-reported and objective sleep/circadian measures was assessed via questionnaires, wrist actigraphy, and measurement of dim light melatonin onset and circadian photoreceptor responsivity. Following this, the number of alcoholic drinks per week and binge drinking episodes per month were assessed quarterly over the subsequent 12 months. Anticipated effects of alcohol (stimulation, sedation, and rewarding aspects) were also assessed quarterly over the 12 months. Analyses included generalized linear mixed-effects models and causal mediation analysis. RESULTS: Across the range of measures, only self-reported insomnia symptoms and a longer total sleep time at baseline predicted more drinks per week and binges per month (ps <0.02). There was a trend for the anticipated alcohol effect of wanting more alcohol at the 6-month timepoint to mediate the relationship between insomnia symptoms at baseline and drinks per week at 12 months (p = 0.069). CONCLUSIONS: These results suggest that in otherwise healthy adults, insomnia symptoms, even if subclinical, are a significant predictor of future drinking, and appear to outweigh the influence of circadian factors on future drinking, at least in otherwise healthy adults. Insomnia symptoms may be a modifiable target for reducing the risk of alcohol misuse.

Circadian photoentrainment varies by season and depressed state: associations between light sensitivity and sleep and circadian timing.

STUDY OBJECTIVES: Altered light sensitivity may be an underlying vulnerability for disrupted circadian photoentrainment. The photic information necessary for circadian photoentrainment is sent to the circadian clock from melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs). The current study tested whether the responsivity of ipRGCs measured using the post-illumination pupil response (PIPR) was associated with circadian phase, sleep timing, and circadian alignment, and if these relationships varied by season or depression severity. METHODS: Adult participants (N = 323, agem = 40.5, agesd = 13.5) with varying depression severity were recruited during the summer (n = 154) and winter (n = 169) months. Light sensitivity was measured using the PIPR. Circadian phase was assessed using Dim Light Melatonin Onset (DLMO) on Friday evenings. Midsleep was measured using actigraphy. Circadian alignment was calculated as the DLMO-midsleep phase angle. Multilevel regression models covaried for age, gender, and time since wake of PIPR assessment. RESULTS: Greater light sensitivity was associated with later circadian phase in summer but not in winter (ß = 0.23; p = 0.03). Greater light sensitivity was associated with shorter DLMO-midsleep phase angles (ß = 0.20; p = 0.03) in minimal depression but not in moderate depression (SIGHSAD < 6.6; Johnson-Neyman region of significance). CONCLUSIONS: Light sensitivity measured by the PIPR was associated with circadian phase during the summer but not in winter, suggesting ipRGC functioning in humans may affect circadian entrainment when external zeitgebers are robust. Light sensitivity was associated with circadian alignment only in participants with minimal depression, suggesting circadian photoentrainment, a possible driver of mood, may be decreased in depression year-round, similar to decreased photoentrainment in winter.