Ancients May Have Been Right that "Humors" Are Linked to Depression According to Study of Seasonal Affective Disorder

A Yale School of Medicine and Veteran’s Affairs Administration study finding that patients with Seasonal Affective Disorder (SAD) have lower nighttime levels of bilirubin, a bile pigment found in the blood and known by ancient Greek physicians as a “humor,” lends support to the humoral theories of mood they espoused.

The study is the first-ever scientific investigation of cyclical, or circadian levels of bilirubin in the blood of people with depression. An abstract of the article is published on the journal Biological Psychiatry’s Web site http://www-east.elsevier.com/bps. The investigators found that nighttime bilirubin levels were lower in nine patients with SAD compared to a group of seven age- and gender-matched, healthy volunteers. The patient group was also found to have increased levels of bilirubin following treatment with exposure to a light source, a standard form of therapy for the disorder.

Principal investigator of the study Dan A. Oren, M.D., Yale associate professor of psychiatry, said, “Humoral theories of mood depending upon bile pigments date back to the dawn of Western medicine. We know of no other studies of circadian bilirubin measurement in seasonal or other forms of depression. Low nocturnal levels of bilirubin may be a clue to understanding the causes and treatment of winter depression.”

According to Oren, SAD affects up to 10 percent of people in the northern United States, and women are more vulnerable to the disorder than men. Unlike other forms of depression, the disorder appears when winter arrives, leaving most sufferers feeling sluggish and weak, with an inexplicable craving for carbohydrates.

Treatment studies of SAD have centered on the effects of light on mood. Scientists know that in humans as in plants, light may play a central role in behavior and that there are biological clocks within all forms of life. Studies show that a strong dose of light from a specialized light unit can often melt winter depression away, but the reasons why light is an effective treatment and how seasonally lower exposure to light may lead to SAD remain a mystery. Oren’s research centers on how light impacts the blood and its association with depression.

Bilirubin, which is found in the blood, is known to be sensitive to light and to be able to cross the blood-brain barrier. It is also known to have a circadian rhythm in which blood levels of bilirubin gradually increase during the night and decrease during the day.

Oren hopes to follow this study with a larger sample of subjects and to study subjects this winter throughout the day and night. This will help determine whether lower levels of bilirubin are a causal factor for SAD or a marker for the disorder.

Funding for the study, which included the work of a former Yale colleague, Dennis Charney, M.D., now of the National Institute of Mental Health (NIMH) in Bethesda, Maryland, came from a Veterans Affairs Career Development Award and a Pilot Grant from the NIMH-supported Yale University Mental Health Clinical Research Center.

Other authors on the study include Yale researchers Paul H. Desan, M.D., Nashaat Boutros and Amit Anand.