An Evaluation of Melanopsin Function and Light Exposure in Depressive Disorders

Abstract

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...