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 Research & Giving News Article  Nearing Two Decades of NARSAD Research During the winter holiday season, we are bombarded with a consistent message from television, radio, movies: this is a time of celebration and joy, a time to feel good cheer and have high spirits. For those suffering from Seasonal Affective Disorder (SAD) however, the shorter, darker days of winter promote quite the opposite state of mind. What is Seasonal Affective Disorder? Seasonal Affective Disorder is a type of depressive mood disorder related to seasonal variations in light. First identified around 1845, SAD was not officially named until the early 1980’s. Sunlight affects the seasonal activities of animals – such as reproductive cycles and hibernation – and scientists suggest that SAD may be an effect of seasonal light variation in humans. As seasons change there is a shift in our internal biological “clock” or circadian rhythm, partly resulting from these changes in sunlight patterns. These shifts can cause our biological clocks to be out of step with our daily schedules and are also linked to depression in some people. SAD is more common in women than men, and usually doesn’t start in people younger than about twenty; as adults get older, the risk of the disorder decreases. Possible Causes Melatonin, a sleep-related hormone secreted by the pineal gland in the brain, is produced at higher levels in the dark, and has been associated with SAD. During shorter days with fewer hours of light, melatonin production increases, and may cause depression. Shifts in the internal biological clock caused by changes in light exposure, may also play a role. A link between circadian clock disorders and psychiatric disease has long been suspected, as people suffering from major depression, bipolar disorder, and SAD often show substantial abnormalities in their sleep-wake cycles. Treatment Because the condition is associated with shorter daylight hours, light therapy is often used to treat SAD. In light therapy, a box outfitted with special lights is used within about ten minutes of waking up in the morning, as sessions at that time of day have been found to have the greatest impact on adjusting and re-regulating the body’s circadian rhythm. In some cases doctors may also prescribe anti-depressants for treating SAD. NARSAD Supports SAD and Body-Clock Research Body-clock research is important for understanding SAD, and also has far reaching implications for other psychiatric disorders. Since the 1980’s, NARSAD scientists have been seeking to better understand the role that melatonin and our internal biological clocks play in mental illness, including seasonal and non-seasonal depression. Among the first NARSAD researchers back in the 1980’s to examine these issues was Sari Gilman-Aronson, M.D., University of Illinois College of Medicine at Urbana-Champaign (1987 Young Investigator, formerly of the University of Pittsburgh). Dr. Gilman-Aronson’s study focused on biological rhythm issues in depression, specifically looking at the body-clock changes that occur in someone suffering from recurrent major depression. She and her colleagues investigated the effects of bright evening light on the sleep and core body temperature of depressed patients. Dr. Gilman-Aronson’s NARSAD funded study allowed her to continue with her experimental research on bright light and circadian rhythms, and laid groundwork for the researchers that followed her in the field. A decade later, Robert D. Levitan, M.D., Centre for Addiction and Mental Health, University of Toronto (1998 & 2000 Young Investigator), took the line of inquiry in a novel direction, looking at a genetic variation in the serotonin system as a possible common thread between Bulimia Nervosa (BN) and SAD. There is strong evidence that the brain chemical, serotonin, plays an important role in eating. There is also significant evidence that abnormalities in serotonin play a role in both bulimia and SAD, disorders that are both characterized by increased food intake. Dr. Levitan studied the genetics of the serotonin system in female patients with bulimia or SAD, a study that yielded important findings for both conditions. In the field of eating disorder research, it has been noted that some bulimia sufferers achieve very low body weights (and may develop anorexia nervosa), while others seem to have a natural limit to their weight loss. Dr. Levitan’s team found a particular gene in the serotonin system that strongly differentiates these two groups of patients, a finding that may have implications far beyond the area of eating disorders. The team’s second compelling finding suggests a possible association between variations in the serotonin-2A receptor gene, childhood Attention Deficit Disorder, and the later development of SAD in women. Dr. Levitan continues his important work on the genetics of disordered eating in bulimia nervosa and SAD, with ongoing investigations into the serotonin and dopamine neurotransmitter systems. D. Alfred Lewy, M.D., Ph.D., Oregon Health Sciences University, (1992 & 2000 Distinguished Investigator), is internationally recognized as a pioneer in the field of human chronobiology (the study of biological rhythms and timing mechanisms, including sleep-wake cycles, heart rate, and body temperature). His first NARSAD study was a 1992 pilot project on using melatonin as a possible treatment of chronobiologic disorder. The resulting data provided important information on optimal dosing and timing of melatonin to help adjust out-of-phase internal clocks. Additionally, this research helped lay the groundwork for his three National Institute of Health (NIH) grants that followed. Dr. Lewy continued research in this area, studying melatonin’s effectiveness in resetting the internal clocks in blind people whose inability to perceive light throws off their bodies’ phases. The groundbreaking results of this work were widely reported by the media, and were published in the October 2000 issue of the New England Journal of Medicine. Dr. Lewy was awarded a second NARSAD grant in 2000, and is studying melatonin as a treatment for non-seasonal depression and bipolar disorder. Another researcher delving into phase-shift adjustment is D. Charles J. Weitz, M.D., Harvard University (1994 Young Investigator, 1999 Independent Investigator), whose research focuses on the molecular biology and genetics of circadian clocks. A NARSAD funded ophthalmologist, Russel N. Van Gelder, M.D., Ph.D., Washington University (2002 Young Investigator), is conducting a study to determine the influence of the circadian clock on affective disorders in mice. His team will perform behavioral testing on mice that have been genetically engineered to have an abnormal or absent circadian clock, as well as “clock-less” and blind mice, monitoring their behavior under constant lighting conditions. The four behavioral tests conducted will include wheel running, the Porsolt forced swimming test (a model of depression), the Morris Swim Maze (a test of spatial learning), and the plus maze (a test of anxious behavior). Using these well-defined animal models, Dr. Van Gelder is directly tackling the question of the influence of the circadian clock on affective disorders. In related work on vision and circadian rhythm, in April 2004 the journal Ophthalmology published Dr. Van Gelder’s findings that individuals who have sustained damage to their optic nerve – which connects the eye to the brain – can experience disordered sleep patterns, in which they feel sleepy during the day, and suffer from insomnia at night. D. Mehmet E. Dokucu, M.D., Ph.D., Washington University (2002 Young Investigator), is also engaged in circadian rhythm research, conducting a genetic and behavioral analysis of lithium’s effect on the body clock. |
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