Light is a powerful antidepressant and is also the most powerful known zeitgeber (time-setter) for the internal biological clocks of the body.
Surprisingly, we still do not know exactly how light works for the treatment of seasonal (SAD) and non-seasonal depression. From a practical point of view, this should not discourage its use. After all, acetaminophen (paracetamol) is one of the most frequently taken medications for treatment of mild pain, and yet scientists still are not exactly sure how it works, either!
Fortunately, with numerous high-quality studies completed worldwide on light’s use for treatment of both seasonal and non-seasonal depression, its place in the therapeutic armamentarium should be considered as strong as for any conventional antidepressant pill, spray or device.
But for those who wish to have a better idea of what might explain light’s antidepressant actions, this article will offer guidance.
Light shifting the clock
For most of the nearly 40 years since SAD (winter depression) was rediscovered and light was shown to be an effective antidepressant, the most popular explanation offered by researchers for light’s therapeutic effects has been the “phase-shift” theory, which argues that light delivered to the eyes has its antidepressant effects by shifting the timing of the biological clock. This is quite plausible, as light — especially in the last hours of nighttime and the first hours of the day — is a powerful zeitgeber. For example, early morning light exposure to the eyes is generally effective for treatment of winter depression. It also causes a “phase advance” of the biological clock, whereby a person exposed to repeated early morning bright light will tend to wake up earlier on subsequent days.
But there are limits to this explanation, as some people respond to bright light treatment in the evening, which has opposite effects on the clock. Furthermore, people with bipolar depression also respond to bright light at mid-day, which has minimal effects on the biological clock. Still, we must remember that SAD patients who got better after bright light treatment typically also advanced their biological clock. So, this correlation became associated with causation. We must conclude that phase advances that shift the clock earlier cannot provide an exclusive explanation of the antidepressant responses.
A pathway that skirts the master clock
Recent work led by researchers at the US National Institutes of Health in a rat model for depression suggests that light’s antidepressant effects work independently of the biological clock. They were able to demonstrate that a precise neural circuit carries a signal of light from the retina to a section of the brain thalamus, bypassing the master circadian clock in the brain hypothalamus. The studies used night-active rodents (as opposed to day-active people), so more work is needed to demonstrate that this pathway is, in fact, directly involved in antidepressant effects in people.
Light to the blood
This writer has been especially interested in another model of how light therapy may have antidepressant effects by acting upon blood passing through the eye. This model was developed after considering that the abundant presence of light-absorbing molecules that regulate the biological clock and activity in plants, and the parallel evolution of similar light-absorbing molecules in animals, raised the question of whether humans might also possess similarly acting molecules — even if animals did not photosynthesize, as is critical to plant life.
The model is based on the century-old knowledge that the light-absorbing center of the chlorophyll molecule has a chemical structure highly similar to the light-absorbing center of the “heme” part of hemoglobin (and some other) molecules.
Hemoglobin is the most abundant visible-light absorbing molecule in the human body and the heme component of the molecule is central to the most critical function of heme-containing molecules, namely the binding and release of gases such as oxygen, carbon monoxide, and nitric oxide. The discovery three decades ago that carbon monoxide and nitric oxide can act as gaseous neurotransmitters (gasotransmitters) in people and that bright light stimulates the release by hemoglobin of these neuroactive gases, and the production by certain proteins of these neuroactive gases, led to the proposal of a model of “humoral phototransduction” whereby light shined on the eyes could increase levels of these gases in blood and deliver an antidepressant effect via the bloodstream to the brain. The biological effect of light in causing increases of these gases in blood was demonstrated more than a century ago; work in the last decade has demonstrated such robust increases can be observed both in pig models and in human blood in test tube studies. Additional work, however, is still required to demonstrate if this pathway is directly responsible for light’s antidepressant effects in people.
We know that ultraviolet light to human skin stimulates the production of Vitamin D. This reaction is well-known to help promote strong and healthy bone growth. Researchers have asked whether Vitamin D might therefore be responsible for the antidepressant effects of light. Since effective light therapy does not require the use of ultraviolet light, it is not likely that that the antidepressant effects work through Vitamin D. Nor has Vitamin D deficiency clearly been shown to be a risk factor for development of winter SAD. Similarly, Vitamin D supplementation not been clearly been shown to be a treatment for winter SAD. So, the role of Vitamin D in light’s antidepressant effects must be considered unclear.
The bottom line
Scientists, light-prescribers, and light-users are therefore still left with uncertainty if they wish to explain exactly how light has its antidepressant effects. But this uncertainty should not be allowed to interfere with the use of this benign and natural environmental treatment. Most of us afflicted by a temporary mild pain will choose not to obsess over our uncertainty about the exact biological mechanism of acetaminophen (paracetamol) if we seek treatment for an ache. Given that acetaminophen is probably far more dangerous than light (especially in overdose), how much less so should we let our uncertainty about light’s exact antidepressant effects block us from prescribing or taking advantage of light’s beneficial effects upon the serious illness state associated with depression.
Dan Oren received the MD degree from the Yale School of Medicine, where he trained in psychiatry, followed by a research fellowship in the Clinical Psychobiology Branch of the US National Institute of Mental Health (NIMH), where he developed his specialty interest in light therapy as a treatment for depression. He is an Associate Professor of Psychiatry at Yale, has served as President of the Society for Light Therapy and Biological Rhythms, and is a member of CET’s Board of Directors. Dan is also a blogger at cet.org, where he explores the causes and treatment of jet lag. His research passion is understanding mechanism of action of light therapy, for which he has proposed a model of “humoral phototransduction” to explain these phenomena on a molecular level.