Philadelphia, PA, September 17, 2007 – Women and men appear to respond differently to the same biochemical manipulation. Major depressive disorder (MDD) is one of the most common mental disorders, and it is also one of the most studied. It is already known that reduced serotonin transmission contributes to the pathophysiology, or functional changes, associated with MDD and most of today’s most popular antidepressants block the serotonin “uptake site”, also known as the transporter, in the brain. It is also known that people with MDD are frequently found to have impaired impulse control. A new study being published in the September 15th issue of Biological Psychiatry now reports on important sex and genetic differences in the way that men and women react to reductions in serotonin function, specifically in terms of their mood and impulsivity.

Using a technique in healthy participants called acute tryptophan depletion, which decreases serotonin levels in the brain, Walderhaug and colleagues found that men became more impulsive, but did not experience any mood changes in response to the induced chemical changes. However, women in this study reported a worsening of their mood and they became more cautious, a response commonly associated with depression. The researchers also discovered that the mood lowering effect in women was influenced by variation in the promotor region of the serotonin transporter gene (5-HTTLPR).

One of the study’s authors, Dr. Espen Walderhaug, explains, “We were surprised to find such a clear sex difference, as men and women normally experience the same effect when the brain chemistry is changed… Although we have the same serotonergic system in the brain, it is possible that men and women utilize serotonin differently.”

These findings highlight the complexity of studying and treating these disorders, as the interactive effects of gender and genetic coding impacted the outcomes in the men and women when their serotonergic functions were disrupted. Dr. Walderhaug comments that their study’s findings “might be relevant in understanding why women show a higher prevalence of mood and anxiety disorders compared to men, while men show a higher prevalence of alcoholism, ADHD and impulse control disorders.” John H. Krystal, M.D., Editor of Biological Psychiatry and affiliated with both Yale University School of Medicine and the VA Connecticut Healthcare System, adds that the response patterns that have emerged in these findings are “the beginnings of an understanding for these sex-related effects.” Ultimately, it is hoped that these findings further advance the ability to quickly and more accurately treat patients.

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Notes to Editors:
The article is “Interactive Effects of Sex and 5-HTTLPR on Mood and Impulsivity During Tryptophan Depletion in Healthy People” by Espen Walderhaug, Andres Magnusson, Alexander Neumeister, Jaakko Lappalainen, Hilde Lunde, Helge Refsum and Nils Inge Landrø. Drs. Walderhaug and Landrø are with the Department of Psychology at the University of Oslo in Oslo, Norway. Dr. Magnusson is affiliated with National University Hospital in Reykjavik, Iceland. Drs. Neumeister and Lappalainen are with Yale University School of Medicine in West Haven, Connecticut. Drs. Lunde and Refsum are affiliated with the Department of Psychopharmacology at Diakonhjemmet University Hospital, Oslo, Norway. The article appears in Biological Psychiatry, Volume 62, Issue 6 (September 15, 2007), published by Elsevier.

Full text of the article mentioned above is available upon request. Contact Jayne M. Dawkins at (215) 239-3674 or ja.dawkins@elsevier.com to obtain a copy or to schedule an interview.

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