By David N. Leff

Swedes, Norwegians and Finns have a double rep: a statistical tendency to suicide and a proclivity to vodka. These unhappy hallmarks correlate with the long winter nights of their sub-Arctic homelands.

In those high latitudes, the sun rises above the horizon during only a scant few hours. This absence of daylight brings on an affliction known to psychiatrists as SAD ¿ seasonal affective disorder. Its more precise moniker is seasonal bipolar depression ¿ SPD.

By either name, the light-deprived affliction kicks in at the same winter point in the calendar, year after year, and spontaneously eases off with the advent of springtime. Its typical symptoms are hypersomnia ¿ oversleeping ¿ low energy, increased appetite with concomitant weight gain, and craving for carbohydrates.

The current therapy for SAD/SPD is not pharmacological but electrical ¿ the common light bulb. Sufferers typically expose their heads to panels lined with illuminating bulbs, and scarf up the light photons lacking from their winter environment.

Where in the body do these bundles of visual energy go, and what do they do there?

A partially blazed pathway starts with the pineal body, a pea-size, pine-cone-shaped gland that lies deep within the fissure dividing the mammalian brain. It produces the hormone melatonin, which is linked to both the sleep-wakefulness and light-dark cycles of circadian (round-the-clock) rhythms.

When the eyes notice that ambient light is growing dim, the pineal gland increases its secretion of melatonin. Serum levels go up 10-fold just before sleep and peak around midnight. Circadian melatonin secretion is higher in winter than in summer. Anecdotal evidence suggests that short courses of the hormone can hasten recovery from transmeridian dysfunction ¿ i.e., jet lag.

That¿s where the story ends so far ¿ at eyesight perception of light. But a research article in the current Journal of Neuroscience, dated Aug. 15, 2001, adds a new dimension to the pathway. It is titled, ¿Action spectrum for melatonin regulation in humans: Evidence for a novel circadian photoreceptor.¿ Its senior author is research neurologist George Brainard, at Thomas Jefferson University in Philadelphia.

Serendipity Finds Fifth Retinal Photoreceptor

¿We have clarified how the human eye uses light to regulate melatonin production,¿ Brainard observed, ¿and, in turn, the body¿s biological clock.¿

He and his co-authors have found clear signs of a novel fifth photoreceptor in the retina ¿ unlike the eye¿s four other light-perceiving receptors. Three of these cone cells control the range of color vision; the fourth regulates night vision. ¿We didn¿t anticipate this fifth photoreceptor cell at all,¿ Brainard remarked.

In their study, the co-authors recruited 72 young volunteers to spend the hours from midnight to 3:30 a.m. exposed to nine different wavelengths of light, from indigo to orange. The cohorts included 37 females and 35 males, whose ages averaged 24.5 years. The participants included 55 Caucasians, 9 Asians, 4 African-Americans, 3 Hispanics and one person of unknown ethnicity.

¿We brought the subjects into the dimly lit laboratory at midnight,¿ Brainard recounted, ¿when melatonin secretion is highest. We dilated their pupils, and blindfolded them for two hours. Then we drew venous blood samples from their arms, and exposed each person to a specific dose of photons of one particular light wavelength for 90 minutes, from 2:00 to 3:30 a.m. Then we drew a second blood sample, both of which were quantified for melatonin secretion.¿

¿For each wavelength studied,¿ the journal paper reported, ¿a set of eight volunteers was exposed to a minimum of eight different light irradiances on separate nights with at least six days between exposures.¿ Their data ¿identified 446-477 nanometers as the most potent wavelength region providing circadian input for regulating melatonin secretion. At the completion of that work, it was determined that a probe below 440 nm was needed. Consequently, a different group of eight subjects was exposed to a single night of no light exposure and a single night of exposure to one irradiance of 420 nm light.¿

The co-authors¿ findings ¿suggest that this new photopigment is retinaldehyde based.¿

(Retinaldehyde is a carotene released in the bleaching of rhodopsin by light and the disassociation of opsin in the vision cycle. Opsin is the protein portion of the rhodopsin molecule, with at least three separate opsins located in the retina¿s cone cells.)

¿In general,¿ the journal article recalled, ¿relatively high light illuminances ranging from 2,500 to 12,000 lux [a measure of candlepower] are used for treating winter depression, selected sleep disorders and circadian disruption. Although these light levels are therapeutically effective,¿ it continued, ¿some patients complain that they produce side effects of visual glare, visual fatigue, photophobia, ocular discomfort and headache. Determining the action spectrum for circadian regulation may lead to improvements in light therapy.¿ (An action spectrum defines the most effective wavelength of light for a given purpose.)

Blue Light Wavelength Clinically Best

In a prior study, earlier this year, Brainard and his co-authors showed that the combined three-cone system didn¿t control the biological effects of light ¿ at least for melatonin regulation. But their subsequent work led to the surprising discovery that a novel photopigment receptor was responsible.

¿We showed,¿ Brainard said, ¿that monochromatic light at 505 nanometers is some four times stronger than 555 nm in suppressing melatonin in healthy humans. In theory, if a clinician wants to use light therapeutically, the blue wavelengths ¿ typically around 450 nm ¿ may be more effective. But if you wanted built-in illumination that would enhance circadian regulation, you might want this wavelength region emphasized. In contrast, if you wanted something that doesn¿t produce biological stimulation, you might steer the light more toward the red wavelengths ¿ in the 650 nm range. But,¿ he pointed out, ¿controlled clinical trials will be needed.

¿This discovery,¿ Brainard suggested, ¿will have an immediate impact on the therapeutic use of light for treating winter depression and circadian disorders. Some makers of light therapy equipment are developing prototypes with enhanced blue light stimuli. In the long range,¿ he concluded, ¿we think this will shape all artificial lighting, whether it¿s used for therapeutic purposes, or for normal illumination of workplaces, hospitals or homes ¿ this is where the impact will be. Broad changes in general architectural lighting may take years, but the groundwork has been laid.¿