The post illumination pupil response is reduced in seasonal affective disorder

Abstract

Individuals with seasonal affective disorder (SAD) may have a decreased retinal sensitivity in the non-image forming light-input pathway. We examined the post illumination pupil response (PIPR) among individuals with SAD and healthy controls to identify possible differences in the melanopsin signaling pathway. We also investigated whether melanopsin gene (OPN4) variations would predict variability in the PIPR. Fifteen SAD and 15 control participants (80% women, mean age 36.7 years, SD = 14.5) were assessed in the fall/winter. Participants were diagnosed based on DSM-IV-TR criteria. Infrared pupillometry was used to measure pupil diameter prior to, during, and after red and blue stimuli. In response to blue light, the SAD group had a reduced PIPR and a lower PIPR percent change relative to controls. The PIPR after the blue stimulus also varied on the basis of OPN4 I394T genotype, but not OPN4 P10L genotype. These findings may indicate that individuals with SAD have a less sensitive light input pathway as measured by the PIPR, leading to differences in neurobiological and behavioral responses such as alertness, circadian photoentrainment, and melatonin release. In addition, this sensitivity may vary based on sequence variations in OPN4, although a larger sample and replication is needed.

Image and Non-Image Forming Melanopsin Function in Age-Related Macular Degeneration

“…SAD may be caused by an abnormal response to seasonal light changes (Bunney & Bunney 2000) with melanopsin gene variants increasing the risk for SAD in 5% of individuals (Roecklein et al 2009). As the SAD patients had no ocular pathology, the lower PIPR amplitude may be due to irregular light exposure, although this was not measured in that study (Roecklein et al 2013). Our AMD cohort did not report any symptoms of SAD; therefore the reduced PIPR amplitude in our study may be due to pathological ipRGC dysfunction that leads to aberrant inputs to the brain, rather than due to irregular light exposure.…”

“…However, in mice that lack ipRGCs, the aberrant light cycle did not impair mood and learning, demonstrating the ability of light to influence cognitive and mood functions directly through ipRGCs (LeGates et al 2012). In a human study, the PIPR to blue light stimuli in persons with seasonal affective disorder (SAD) was significantly reduced compared to a control group, indicating reduced ipRGC sensitivity (Roecklein et al 2013). Further, persons with gene variants (rs2675703, P10L, TT allele) in the melanopsin (opn4) photopigment had a 5.6 times higher risk of developing SAD (Roecklein et al 2009).…”

“…Studies in melanopsin knock-out mice show sleep disturbances where they sleep for approximately one hour less than wild-type mice (Tsai et al 2009) while human studies show that ipRGC deficits are associated with sleep disorders in glaucoma (Gracitelli et al 2015) and their function is reduced in seasonal affective disorder (Roecklein et al 2013). With the high prevalence of depression in AMD (Brody et al 2001;Casten & Rovner 2013) and altered sleep duration that is dependent on AMD type (wet or dry) (Khurana et al 2016;Pérez-Canales, Rico-Sergado & Pérez-Santonja 2016), ipRGC dysfunction in AMD may contribute to these disorders.…”

“…IpRGCs project to brain areas implicated in mood regulation (LeGates et al 2012) and patients with seasonal affective disorder (SAD) have a dysfunctional melanopsin mediated PIPR (Roecklein et al 2013), indicative of a role of aberrant ipRGC signalling in the presence of SAD. In mouse models, depression related behaviour in wild type mice is observed in response to an altered light and dark cycle but not in ipRGC deficient mice (LeGates et al 2012), demonstrating the ability of light signalling via ipRGCs to influence mood.…”

“…However no correlation between ipRGC function and depression in advanced AMD was found; hence our hypothesis for a causal relationship between these cells' dysfunction and altered signalling to mood centres could not be evaluated in this sample. Irregular light exposure can influence cognitive and mood functions directly through ipRGCs (LeGates et al 2012) as demonstrated in patients with SAD who have a reduced PIPR amplitude (Roecklein et al 2013). SAD may be caused by an abnormal response to seasonal light changes (Bunney & Bunney 2000) with melanopsin gene variants increasing the risk for SAD in 5% of individuals (Roecklein et al 2009).…”