Bilirubin, REM sleep, and phototransduction of environmental time cues. A hypothesis.

The prevailing hypothesis for phototransduction is that visual (rod or cone) pigments mediate light's primary effects on biological clock systems. Common light-responsive chronobiological behavioral properties of plants and animals and some common molecular structures of plants and animals suggest the possibility that heme moieties and bile pigments in animals mediate some nonvisual influences of light on neuroactive gases and biological rhythms. As plant phytochrome resets the plant biological clock, the similar chromophore in bile pigments is proposed to transduce environmental light zeitgeber signals to endogenous biological clocks. The temporal association of plasma bilirubin and rapid-eye-movement (REM) sleep in populations, the correlation of secretion of biliary bilirubin with REM sleep among 10 different species (Spearman r = 0.89, p < 0.002), and the known responses of bilirubin to light lead to the hypothesis that bilirubin, in particular, plays an evolutionary role in the regulation of REM sleep and in mediating some of light's antidepressant effects.