Pupillary response abnormalities in depressive disorders

Abstract

Depressive disorders lack objective physiological measurements to characterize the affected population and facilitate study of relevant mechanisms. The melanopsin-mediated light signaling pathway may contribute to seasonal variation and can be measured non-invasively by pupillometry. We prospectively studied changes in melanopsin-mediated pupillary constriction in 19 participants with major depressive disorder (MDD) and 10 control across the summer and winter solstices. The melanopsin-mediated response, as measured by the pupil's sustained constriction six s after a high intensity blue light stimulus, was marginally attenuated in those with MDD relative to controls (p=0.071). The participants with MDD unexpectedly showed a significantly reduced transient pupillary response to low intensity red (p=0.011) and blue light (p=0.013), but not high intensity red and blue light. Sustained pupillary constriction in response to high intensity blue light was more pronounced with increasing daylight hours (p=0.037) and was more strongly related to objectively measured versus estimated light exposure. Melanopsin-mediated impairments in pupil response may serve as a biological marker for vulnerability to depression in low light conditions. Assessment of these and other responses to light stimuli, such as response to low intensity light, may be useful for the study of the neurobiology of MDD and related mood disorders.

An Evaluation of Melanopsin Function and Light Exposure in Depressive Disorders

“…A recent study, however, observed no difference in the PIPR in patients with MDD including SAD compared to healthy individuals (Laurenzo et al, 2016). The discrepancy in the PIPR results among the patients with depression between the two studies may have occurred due to the PIPR measurements in the (Laurenzo et al, 2016) study being conducted during both the winter and summer months when depression and remission occur respectively, possibly altering the melanopsin function with season (Münch, Kourti, Brouzas, & Kawasaki, 2016).…”

“…Several studies have linked the role of the recently discovered inner retinal melanopsinexpressing intrinsically photosensitive Retinal Ganglion Cells (ipRGCs) to the regulation of effect of light on mood and cognitive functions in humans (Laurenzo, Kardon, Ledolter, Poolman, Schumacher, Potash, Full, Rice, Ketcham, Starkey, & Fiedorowicz, 2016;Roecklein, Wong, Ernecoff, Miller, Donofry, Kamarck, Wood-Vasey, & Franzen, 2013) and animals (Legates, Altimus, Wang, Lee, Yang, Zhao, Kirkwood, Weber, & Hattar, 2012).…”

“…The measurement of the PIPR allows for the direct and in vivo assessment of ipRGC function in humans (Adhikari et al, 2015b;Feigl & Zele, 2014;Gamlin et al, 2007;Kankipati et al, 2010;Markwell et al, 2010;McDougal et al, 2010;Young et al, 2008). Collectively, the PIPR has been assessed as a direct and non-invasive biomarker of ipRGC function in human eyes with and without retinal disease (Adhikari, Zele, Thomas, & Feigl, 2016b;Feigl, Mattes, Thomas, & Zele, 2011;Feigl et al, 2014;Feigl, Zele, Fader, Howes, Hughes, Jones, & Jones, 2012;Kankipati et al, 2010;Kankipati, Girkin, & Gamlin, 2011;Kelbsch, Maeda, Strasser, Blumenstock, Wilhelm, Wilhelm, & Peters, 2016;Markwell et al, 2010;Maynard, Zele, & Feigl, 2015) and therefore can also be used to measure the input of ipRGC projections to the brain mood centres to evaluate the melanopsin function in depressive disorders (Laurenzo et al, 2016;Roecklein et al, 2013).…”

“…In particular, Laurenzo et al (2016) demonstrated that the PLR to low intensity short and long wavelength light stimuli, which preferentially reflects the outer retinal photoreception when measured using the transient pupil response (Adhikari et al, 2015b;Feigl et al, 2012;Kardon, Anderson, Damarjian, Grace, Stone, & Kawasaki, 2009), is reduced in patients with MDD. Although, the PIPR and transient PLR in response to a high-intensity and short wavelength light stimulus have a significant positive relationship with light exposure in MDD (Laurenzo et al, 2016), no study has compared the ambient light exposure through 24 hours in a day in individuals with and without non-seasonal MDD.…”

“…Although, the PIPR and transient PLR in response to a high-intensity and short wavelength light stimulus have a significant positive relationship with light exposure in MDD (Laurenzo et al, 2016), no study has compared the ambient light exposure through 24 hours in a day in individuals with and without non-seasonal MDD. Treatment of depression with ocular light exposure is commonly provided through light levels ranging from 2500 to 10,000 lux (Even, Schröder, Friedman, & Rouillon, 2008;Gallin, Terman, Reme, Rafferty, Terman, & Burde, 1995;Glickman et al, 2006;Haffmans, Schouten, & den Hoed, 2008;Kräuchi, Wirz-Justice, & Graw, 1990;Meesters et al, 2011;Naus, Burger, Malkoc, Molendijk, & Haffmans, 2013;Szabó et al, 2004;Winkler, Pjrek, Praschak-Rieder, Willeit, Pezawas, Konstantinidis, Stastny, & Kasper, 2005;Wirz-Justice, Graw, Roosli, Glauser, & Fleischhauer, 1999), but no study has evaluated the habitual exposure durations to these ranges of illuminance of ambient light in patients with non seasonal depressive disorders.…”