Is it that time of the month? These are the words no man should ever utter. How about this for a diplomatic alternative: “Are your GABA receptors playing up?”

You may be spot on. It seems that these brain cells are to blame for some women’s monthly mood swings.

Many women feel a little irritable before menstruating, but up to 8 per cent suffer extreme symptoms, including anxiety, depression and fatigue.

Symptoms of what’s called premenstrual dysphoric disorder (PMDD) begin around a week before menstruation when women are in the “late luteal phase” of their cycle and progesterone levels are at their height. Symptoms quickly subside after menstruation, once the so-called “follicular phase” has kicked in.


To investigate potential mechanisms behind PMDD, Andrea Rapkin at the University of California, Los Angeles used a PET scan, which shows where glucose is being metabolised to identify activity in the brain. The idea was to analyse the brain activity of 12 women with PMDD and 12 without the condition, at various times throughout their menstrual cycle.

Before each scan, the women rated the severity of any symptoms they had on a scale of one to six. Blood samples were also taken to test their hormone levels.

Fluctuating hormones were not to blame: all the women experienced similar jumps in progesterone levels throughout their cycle, irrespective of whether they had PMDD or not.

However, brain analyses showed that in the late luteal phase women with PMDD had heightened activity in their cerebellum. Rapkin also discovered that the larger the spike in activity, the worse the symptoms.

Women without PMDD had no such spike in activity, even though their progesterone levels were also rising during this time.

Over-sensitive

Animal studies have shown that progesterone can change the shape of receptors present in the cerebellum, which forms connections with the limbic and prefrontal cortices, which are responsible for controlling emotion and behaviour. Changes to the receptors make them less receptive to a chemical called GABA.

GABA is the brain’s main inhibitory molecule – the “off” signal for neurons. One of its functions in the brain is to limit activity associated with stress and anxiety.

Rapkin suggests that in PMDD, progesterone alters the shape of GABA receptors in the cerebellum, making it harder for GABA to bind to them and damp down anxiety.

Lorraine Dennerstein a psychiatrist at the University of Melbourne, Australia, who researches the relationship between ovarian hormones and women’s mood, suspects that women with PMDD and premenstrual syndrome have GABA receptors that are particularly sensitive to progesterone, and so change shape easily.

Suzanne Abraham, a gynaecologist at Royal North Shore Hospital in Sydney, Australia, says that PMDD was not taken seriously as a condition, but this study confirms it “is ‘real’ and can be measured”, she says.

Journal reference: Biological Psychiatry, DOI: 10.1016/j.biopsych.2010.09.029