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.

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.

Sleep and circadian rhythm profiles in seasonal depression.

Sleep and circadian rhythm disruptions are symptoms of, and hypothesized underlying mechanisms in, seasonal depression. Discrepant observational findings and mixed responses to sleep/circadian-based treatments suggest heterogenous sleep and circadian disruptions in seasonal depression, despite these disruptions historically conceptualized as delayed circadian phase and hypersomnia. This study used a data-driven cluster analysis to characterize sleep/circadian profiles in seasonal depression to identify treatment targets for future interventions. Biobehavioral measures of sleep and circadian rhythms were assessed during the winter in individuals with Seasonal Affective Disorder (SAD), subsyndromal-SAD (S-SAD), or nonseasonal, never depressed controls (total sample N = 103). The following variables were used in the cluster analysis: circadian phase (from dim light melatonin onset), midsleep timing, total sleep time, sleep efficiency, regularity of midsleep timing, and nap duration (all from wrist actigraphy). Sleep and circadian variables were compared across clusters and controls. Despite limited sleep/circadian differences between diagnostic groups, there were two reliable (Jaccard Coefficients >0.75) sleep/circadian profiles in SAD/S-SAD individuals: a 'Disrupted sleep' cluster, characterized by irregular and fragmented sleep and an 'Advanced' cluster, characterized by early sleep and circadian timing and longer total sleep times (>7.5 h). Clusters did not differ by depression severity. Midsleep correlated with DLMO (r = 0.56), irregularity (r = 0.3), and total sleep time (r = -0.27). Sleep and circadian disruptions in seasonal depression are not uniformly characterized by hypersomnia and circadian phase delay. Presence of distinct sleep and circadian subgroups in seasonal depression may predict successful treatment response. Prospective assessment and tailoring of individual sleep and circadian disruptions may reduce treatment failures.