Approximately 5 million women suffer from premenstrual dysphoric disorder (PMDD) in the United States. The symptoms of this disorder include depressed mood, irritability, fatigue, and sleep disturbances and have a significant impact on wellbeing and productivity, with estimated direct medical costs of 295 million dollars and indirect costs to employers of 21 billion dollars per year. Despite the inclusion of 'hypersomnia or insomnia' among the diagnostic criteria for PMDD, few studies have investigated the nature of sleep disturbance in women with PMDD. Further, our understanding of the etiology and mechanisms driving this hormonally-linked disorder is limited. The first specific aim of the proposed study is to use sensitive measures of arousal and sleep electroencephalographic (EEG) activity to delineate the extent of sleep disturbance in the luteal phase in women with PMDD in order to clarify its role as a symptom of the disorder. The second specific aim is to explore the gamma amino butyric acid (GABA) system as a potential mechanism of PMDD by quantifying spindles (12 -15 Hz activity) in the sleep EEG. These spindles originate as oscillations generated by GABAergic neurons in the thalamus and their potential as a sensitive marker of GABAergic function in women with PMDD is supported by our pilot data.
Both specific aims will be addressed by testing women with PMDD (N=25) and controls (N=25) in a study in which overnight sleep EEG is recorded in the mid-follicular, mid-luteal, and late-luteal phases of the menstrual cycle. We predict that spindle frequency activity will be increased in the luteal phase compared to the follicular phase in all women, regardless of diagnosis, and will be greater during both phases of the menstrual cycle in women with PMDD than controls. Probing PMDD with measures of GABAergic function, such as spindle frequency activity, will not only contribute to our understanding of this disorder but may also provide insight into novel treatment options for PMDD through manipulation of the GABAergic system. Insights into the pathophysiology of PMDD may also be informative for women experiencing depression at other phases of the reproductive cycle such as post-partum and during the menopausal transition. Premenstrual Dysphoric Disorder (PMDD) is a debilitating disorder that affects women of reproductive age. The etiology of PMDD is still poorly understood. This study will clarify the role of sleep disturbance in PMDD and will also provide insight into the role of the GABA system in the etiology of PMDD, which may lead to novel treatment options in the future. ? ? ?
