HSC RESEARCH SEEKS ANSWER TO PMDD TRIGGER

July 1, 2003

Health science center researchers are trying to identify a possible cause of premenstrual dysphoric disorder (PMDD), which may aid in the development of new treatments.

Meharvan Singh, PhD, assistant professor of pharmacology and neuroscience, is the principal investigator in a study funded by a $60,000 grant from the National Alliance for Research in Schizophrenia and Depression and a $15,000 UNTHSC faculty research grant.

Dr. Singh and Glenn Dillon, PhD, associate professor of pharmacology and neuroscience, are investigating the interaction between the hormone progesterone and the GABAA receptor, a protein that, when activated, acts as the main â??brakeâ? that helps tone down the activation, or firing, of nerve cells in the brain.â??The symptoms of PMDD are related to premenstrual syndrome, but are so severe that they often interfere with a womanâ??s daily life,â? Dr. Singh said.

The disorder affects 3 to 8 percent of women, generally those in their 20s and 30s. Symptoms, including severe depression, irritability and mood swings, start seven to 14 days before menstruation and end a few days after menstruation begins, according to Medem, an online medical library founded by the nationâ??s leading medical societies.

â??Historically, PMDD was thought to be due to reduced progesterone levels. However, the period when women are most susceptible to the symptoms of PMDD is when progesterone levels are high,â? Dr. Singh said. â??So, if you think of the symptoms of PMDD as a state of hyper-anxiety or extreme excitability, this state may be toned down if you activate the GABA-A brake. Alternatively, the symptoms could become evident or worsen if you block the brake,â? he said.

Drs. Singh and Dillon have found that progesterone directly inhibits, or shuts off, the braking activities of the GABA-A receptor, which may trigger PMDD symptoms in some women. They believe that this inhibition of GABA-A is part of the biology of PMDD, and their research focuses on understanding the processes by which progesterone inhibits GABA-A.

â??Understanding the biology of PMDD is important because it allows us to come up with new treatment strategies,â? Dr. Singh said. â??PMDD is a multifaceted disorder, but the interaction between progesterone and GABA-A could be a therapeutic target. Understanding the basic science aspects of the relationship between these two elements is potentially relevant to developing clinical treatments for PMDD.â?

More specifically, Drs. Singh and Dillon are investigating the connection between a certain signaling, or communication, pathway and its influence on the GABA-A receptor. This pathway, called the MAPK pathway, is activated by progesterone.

Signaling pathways are characterized by the sequential activation of proteins within a cell that tell the cell what to do or how to respond when a hormone or drug arrives at its surface, Dr. Singh said.

The researchers believe the MAPK pathway is one of the ways progesterone communicates with the GABA-A receptor. â??If we can understand how the MAPK pathway facilitates communication between progesterone and GABA-A, the pathway may also be a potential target for therapy. Understanding the communication mechanism may allow us to alter the communication,â? Dr. Singh said.

NARSAD is exclusively devoted to supporting research on brain and behavior disorders, according to its web site. It supports scientists around the world who study the causes and treatment of severe psychiatric disorders.

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John Licciardone Hsc Fort Worth Fc
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