Innovative, alternative treatments are needed for Premenstrual Dysphoric Disorder (PMDD), a disabling depressive disorder listed in DSM-IV, affecting 5-8% of menstruating women. Left untreated, PMDD can progress to major depression. Offered medication, at least 40% of women do not respond, develop problematic side-effects or seek options other than chronic pharmacological treatment for this periodic illness. Previously we independently administered sleep and light behavioral therapies, translating discoveries from basic circadian biology to improve the health of women with PMDD. In response to a call for the development of novel combination therapies, in this proposal we plan to co-administer wake therapy followed by light treatment, a novel alternative approach, never before tried in PMDD, despite its demonstrated efficacy in other mood disorders. These potentially complementary treatments have the advantage of wake therapy hastening the onset of the antidepressant effects of light treatment, a crucial benefit during the relatively short-lived symptoms of the 2-week luteal phase, whereas light treatment maintains the benefit of the otherwise transitory effects of wake therapy often lost after subsequent sleep. Our primary aim is to examine the effects of these interventions on mood, and secondarily on circadian rhythms, to test the hypothesis that critically-timed chronotherapy improves mood by correcting phase disturbances in melatonin and sleep. As we found that in PMDD melatonin rhythms were phase-delayed (shifted-later) in the symptomatic luteal compared with the asymptomatic follicular, menstrual cycle phase, we hypothesize that advancing melatonin rhythms with late wake therapy (LWT: sleep 21:00-01:00 h, followed by wake) plus morning bright white light (BWL) will improve mood in PMDD patients more than delaying them with early wake therapy (EWT: wake, then sleep 03:00-07:00 h) plus evening BWL. Outcome measures are mood, urinary melatonin, sleep/activity in PMDD subjects. These studies will determine whether innovative, alternative, combined chronobiological interventions, targeted to specific underlying circadian rhythm abnormalities, can benefit mood in PMDD. The results may impact other depressive disorders with chronobiological disturbances and other women?s mood disorders.

Public Health Relevance

Premenstrual Dysphoric Disorder (PMDD) is a disabling disorder for which current treatments are insufficient. In this proposal, we plan to investigate novel sleep and light therapies, which have never before been used in PMDD, but which are safe and efficacious treatments in other mood disorders. We plan to apply a combination of these treatments to women with PMDD and to investigate how they might work by altering biological rhythms so as to prevent women developing major depression or exacerbating pregnancy, postpartum or menopausal depressions.

National Institute of Health (NIH)
Research Project (R01)
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Biobehavioral Mechanisms of Emotion, Stress and Health Study Section (MESH)
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Alekel, D Lee
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University of California San Diego
Schools of Medicine
La Jolla
United States
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