Background: Melanopsin-expressing intrinsically photosensitive Retinal Ganglion Cells (ipRGCs) signal non-imaging forming effects of environmental light for circadian phoentrainment, the pupil light reflex, and mood regulation. In seasonal affective disorder, ipRGC dysfunction is thought to cause abberant transmission of the external illumination for photoentrainment. It is not known if patients with non-seasonal depression have abnormal melanospin mediated signaling and/or irregular environmental light exposure.Methods: Twenty-one adults who live in a sub-tropical region, including eight patients with non-seasonal depression and thirteen age-matched healthy controls were recruited. The Mini International Neuropsychiatry Interview diagnosed the presence of a major depressive disorder. Light exposure was determined using actigraphy over a 2 week period. The melanopsin mediated post-illumination pupil response (PIPR) and outer retinal inputs to ipRGCs (transient pupil response and maximum pupil constriction amplitude) were measured in response to 1 s, short and long wavelength light with high and low melanopsin excitation.Results: The mean daylight exposure as a function of clock hours and total light exposure duration (mins) to illumination levels commonly recommended for depression therapy were not significantly different between groups. Out of 84 pupil measurements (42 each in the depression and control groups), the melanopsin-mediated PIPR amplitude, transient pupil response, and pupil constriction amplitude were not significantly different between groups.Conclusions: This report provides initial evidence of normal melanopsin function and environmental light exposures in patients with pre-dominately mid and moderate non-seasonal depression in a subtropical location in the southern hemisphere.

Aberrant light exposure causes depression in animals through a pathway involving the recently discovered intrinsically photosensitive Retinal Ganglion Cells (ipRGCs). The photopigment melanopsin expressed in ipRGCs encodes irradiance to signal to the nonimage-forming centres of the brain, including the suprachiasmatic nucleus (SCN) for circadian photoentrainment and the olivary pretectal nucleus (OPN) to control the pupil light reflex. Mouse models have further identified ipRGC projections to the brain nuclei that regulate mood and behaviour. In humans, the post-illumination pupil response (PIPR), a sustained pupillary constriction after light offset, is used as a direct and non-invasive biomarker of ipRGC function.The PIPR amplitude is reduced in humans with seasonal affective disorder (SAD) that shows a seasonal variation in depressive episodes with a peak manifestation in winter when the solar light exposure is low, but a recent study including patients with non-seasonal depressive disorder did not detect ipRGC dysfunction. Moreover, neither study measured the ambient light exposure levels in patients with depression for comparison to healthy individuals without depression. The knowledge of the role of light coding cells (ipRGCs) in major depressive disorder (MDD) is incomplete unless the relationship between ambient light exposure levels and melanopsin function is evaluated. This study aims to measure the environmental light exposure levels and their relationship with melanopsin-mediated PIPR in non-seasonal depression. It is hypothesised that the patients with non-seasonal depression are exposed to low light levels and this is associated with impaired melanopsin function.A sample of 22 adults was recruited, including people with non-seasonal depression (n = 8, median age: 35 years) and healthy age-matched controls (n = 14, median age: 29 years).The presence of a DSM-IV MDD was assessed using the Mini International Neuropsychiatry ii Interview (MINI 6). The severity of depression symptoms was assessed with the Beck Depression Inventory (BDI-II). Individuals with recurrent MDD assessed with the MINI and a positive screen on the Seasonal Pattern Assessment Questionnaire and the Hamilton Depression Rating Scale-SAD (HDRS-SAD) were excluded as SAD. Both groups had visual acuity ≥ 6/6, normal colour vision and intraocular pressure (IOP) ≤ 21 mmHg, no corneal and lenticular opacities and normal retinae and optic discs. The ipRGC-mediated PIPR was measured using a short duration (1 s) high irradiance (15.5 log quanta.cm -2 .s -1 ) short wavelength (blue appearing) light stimulus with a custom built Maxwellian view pupillometer. Light exposure levels, sleep-wake times and sleep efficiency were determined over 2 weeks with an ambulatory light sensor device (Geneactive).The mean daily light exposure levels were similar between the groups and there were no statistically significant differences between the groups for light exposure levels as a function of clock hours, nor in the total number of minutes of exposu...