Wendy's mysterious symptoms "really reared their ugly head" after she suffered a deep bout of postpartum depression following the birth of her first child 16 years ago.
When she recovered, she was plagued by a host of ailments -- from severe mood swings and anxiety to memory loss and fatigue -- that worsened as the years went by.
The 49-year-old Edmonton woman's emotions became so volatile that she could no longer watch movies, a favourite family pastime, because she would cry hysterically at both the happy and sad parts.
"You don't feel in control at all -- of your emotions, your moods -- and then that affects your behaviour and even your attitude," said Wendy, who asked to be referred to by her first name to protect her family's privacy.
At some point, she realized the debilitating symptoms came like clockwork in the days and weeks before her period and faded after it started.
Despite consulting several doctors, none could pinpoint the root of her symptoms, which she figured were related to premenstrual syndrome. Most diagnosed her with depression, but the label didn't feel right.
As her condition got worse, so did her family life. The mother of two battled regularly with her son. She and her husband, who initially discounted PMS, decided not to have a third child. She felt incapable of returning to her teaching job, which she left when she had her first baby.
After searching for years, Wendy was diagnosed last fall with a controversial and little-known extreme form of PMS called premenstrual dysphoric disorder, or PMDD. Many call it "PMS from hell."
"They very often feel like a different person; that's how those ladies usually describe themselves," said Janette Seres, a post-doctoral fellow who studies the condition at the University of Alberta. "Usually they come and say, 'You know, I'm crazy for two weeks.' And it's good for them to know, 'Okay, this is a disorder, this is a known problem.' "
PMDD, which is considered a mental disorder, is characterized by disabling emotional symptoms that are so severe they interfere with normal life. Researchers estimate that the syndrome, which tends to intensify as sufferers get older, affects 2 to 7 per cent of women in their reproductive years. Such women are also predisposed to other psychiatric conditions, including depression.
Women with PMDD -- who can also experience strong food cravings, sadness, lack of interest in regular activities, insomnia, anxiety and difficulty concentrating -- live a roller-coaster existence. Symptoms vary during their menstrual cycles, tending to be worst up to two weeks before their periods and virtually disappearing afterward.
Many experts believe the symptoms are triggered when natural hormones that fluctuate during the menstrual cycle interact with brain chemicals that are somehow altered in women with the disorder.
These changes set off "severe behavioural modification and emotional symptoms," said Jean-Michel Le Mellédo, a psychiatrist and director of the University of Alberta's brain neurobiology program.
However, the disorder, whose legitimacy is the subject of heated debate, is not considered a full-fledged condition in the current edition of the Diagnostic and Statistical Manual of Mental Disorders, which is psychiatry's bible. Instead, PMDD appears in the appendix, which lists potential disorders "proposed for further study."
Dr. Le Mellédo and Dr. Seres, who are convinced that PMDD exists, are conducting three studies in hopes of discovering its cause and eventually an effective treatment.
(Wendy was prescribed a selective serotonin reuptake inhibitor, a class of drugs that includes Prozac and Paxil, which is also used to treat depression. However, she stopped taking the medication so she could participate in Dr. Le Mellédo and Dr. Seres's research.)
The scientists believe two brain chemicals called GABA and glutamate are altered in women with PMDD. They are trying to figure out the interaction between the chemicals and female hormones, such as progesterone and allopregnanalone, which fluctuate during the menstrual cycle.
Women who participate in the studies -- which are funded by the University of Alberta Hospital Foundation, the Canadian Institutes of Health Research and a drug company that pays part of Dr. Seres's salary -- are asked to keep a diary of their symptoms during two menstrual cycles, which is an important tool in diagnosing them.
"The ladies usually love these diaries," Dr. Seres said. "They can see on paper . . . how these symptoms change."
One of their projects, the only one of its kind in Canada, involves measuring GABA and glutamate in parts of the brains of PMDD women that are associated with emotions. Using a powerful MRI machine, the team uses magnetic resonance spectroscopy, a sophisticated method to measure the chemicals.
The process is done four times during sufferers' cycles -- when they have symptoms and also when they do not -- to see if their brain chemicals are always altered or only when they suffer PMDD's effects. (Women who do not have the disorder are also studied as controls.)
In another project, the researchers use flumazenil, a chemical that binds to GABA and allows study of its effect on women with PMDD. Those who have the disorder experience "short-lived panic symptoms" after flumazenil is administered while healthy women do not, Dr. Seres said.
The third study, which is the newest and also the only one of its kind in Canada, focuses on the possibility of a hereditary component of PMDD. DNA from sufferers and their parents is studied for abnormalities.
"If you want to find the treatment," Dr. Seres said, "first we have to know what's wrong."