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Reviews and Overviews   |    
SAD and the Not-So-Single Photoreceptors
Dan A. Oren, M.D.; Marek Koziorowski, D.V.M., Ph.D.; Paul H. Desan, M.D., Ph.D.
Am J Psychiatry 2013;170:1403-1412. doi:10.1176/appi.ajp.2013.13010111
View Author and Article Information

Dr. Oren consulted for 2 hours in 2012 to a light therapy device manufacturer (Litebook Company); he received no financial support contributing to the time or work preparing this article. Dr. Desan has received research support for clinical trials of phototherapy devices for SAD from the Litebook Company in the last 36 months. Dr. Koziorowski has no financial relationship with commercial interests.

From the Department of Psychiatry, School of Medicine, Yale University, New Haven, Conn.; and the Institute of Applied Biotechnology and Basic Sciences, University of Rzeszów, Rzeszów, Poland.

Address correspondence to Dr. Oren (doren@aya.yale.edu).

Copyright © 2013 by the American Psychiatric Association

Received January 25, 2013; Revised May 17, 2013; Accepted May 28, 2013.

Abstract

Research in the last century has demonstrated that light is a critical regulator of physiology in animals. More recent research has exposed the influence of light on human behavior, including the phenomenon of seasonal affective disorder (SAD). Repeated studies have shown that light treatment is effective in this disorder. The molecular mechanism by which the body absorbs the light that has energizing and antidepressant effects is still uncertain. This review presents evidence regarding the role of rod and cone photoreceptors, as well as the role of recently discovered nonvisual neuronal melanopsin-containing photoreceptors. The authors discuss an evolutionary-based theoretical model of humoral phototransduction. This model postulates that tetrapyrrole pigments, including hemoglobin and bilirubin, are blood-borne photoreceptors, regulating gasotransmitters such as carbon monoxide when exposed to light in the eye. Recent studies in an animal model for seasonality provide data consistent with this model. Understanding the molecular mechanisms by which light affects physiology may guide the development of therapies for SAD and other pathologies of circadian and circannual regulation.

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FIGURE 1. Anatomy of the Human Cavernous Sinus, Emphasizing Central Retinal Vein Drainage to the Venous Plexus Surrounding the Internal Carotid Arterya

a Illustration by Jeanette Kuvin Oren; adapted from reference 63.

FIGURE 2. Concentration of Carbon Monoxide (CO) in the Venous Blood Outflow From the Eye and Nasal Areas of the Wild Boar-Pig Hybrid During Long- and Short-Photoperiod Daysa

a Adapted from reference 65; reprinted by permission of Biolife S.A.S.

b Morning and afternoon ophthalmic venous CO concentrations both significantly higher than the nasal venous CO concentrations and higher than the nocturnal ophthalmic venous concentration (N=8, p<0.05).

c Daytime and nocturnal ophthalmic venous CO concentrations both significantly higher than the nasal venous concentrations (N=8, p<0.05).

FIGURE 3. Degradation Pathway of Heme in Mammals, Emphasizing Enzymatic and Structural Chemical Pathways Known To Be Sensitive to Bright Lighta

a Bilirubin’s activity as an antioxidant is demonstrated by its own oxidation back to biliverdin (75).

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Self-Assessment Quiz

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1.
Which photoreceptor molecules have been proven to regulate circadian rhythms in mammals?
2.
Which known conserved behavior of plants and animals provides a conceptual framework for the “humoral phototransduction” model?
3.
Which seasonal effects upon blood have been observed in an experimental animal?
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