Pregnant and postpartum major depression (MD) has disabling effects on the mother and her family, and impairs growth and neurocognitive development of the child. Investigation into its pathogenesis, with the ultimate aim of developing new treatment strategies, is needed urgently, particularly given the limited safety and efficacy of treatment options documented in pregnant and in lactating women. In previous work, we demonstrated that pregnant depressed patients (DP) had phase-advanced (shifted-earlier), whereas postpartum DP had phase-delayed (shifted-later) melatonin rhythms compared with normal control (NC) pregnant or postpartum women. In this new application we will test the hypothesis that correcting these underlying circadian rhythm disturbances with a combination of appropriately-timed wake therapy and light treatment achieves antidepressant effects. We expect treatments to act selectively: In pregnant DP with phase- advanced rhythms, we hypothesize that early wake therapy (EWT: wake until 03:00 h, followed by sleep until 07:00 h) plus evening (PM) bright white light (BWL), which phase-delay melatonin rhythms, will improve mood more than late wake therapy (LWT: sleep from 21:00-01:00 h, followed by wake) plus morning (AM) BWL, which phase-advance melatonin rhythms. In contrast, in postpartum DP with phase-delayed rhythms, we hypothesize that LWT plus AM BWL, which phase-advance melatonin rhythms, will improve mood more than EWT plus PM BWL, which phase-delay them. These combined chronobiological treatments are complementary in that wake therapy can hasten and potentiate the antidepressant effects of light treatment that may take up to 10 weeks to show efficacy in pregnant DP, while light treatment can sustain the antidepressant effects of wake therapy that often are lost after subsequent sleep. Although these combined treatments have demonstrated safety and efficacy in other mood disorders, they have not been applied to pregnant and postpartum MD. We will examine the effects of EWT plus PM BWL vs. LWT plus AM BWL on mood, urinary melatonin and the sleep/wake cycle in pregnant and postpartum DP at home. By this translational approach targeted to underlying chronobiological abnormalities, we aim to develop innovative alternative interventions for puerperal MD, potentially transforming treatment approaches for women's mood and other disorders with circadian rhythm disturbances.

Public Health Relevance

Depression during pregnancy or after delivery (postpartum) can impair the health of the mother and her child. Drug treatments often cause problematic side effects both during pregnancy and during breast-feeding. The aims of this study are to develop new, safe and efficacious treatments involving sleep and light therapies that can improve mood in depressed women during pregnancy and postpartum and to investigate how they might work by altering biological rhythms.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Biobehavioral Mechanisms of Emotion, Stress and Health Study Section (MESH)
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Reddy, Uma M
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University of California San Diego
Schools of Medicine
La Jolla
United States
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