Shiro Suda1, Eri Segi-Nishida, Samuel S Newton, Ronald S Duman. 1. Division of Molecular Psychiatry, Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, Yale University School of Medicine, New Haven, Connecticut 06508, USA.
Abstract
BACKGROUND: Postpartum depression (PPD) affects approximately 10% to 20% of women during the first 4 weeks of the postpartum period and is characterized by labile mood with prominent anxiety and irritability, insomnia, and depressive mood. During the postpartum period, elevated ovarian hormones abruptly decrease to the early follicular phase levels that are postulated to play a major role in triggering PPD. However, the underlying neurobiological mechanisms that contribute to PPD have not been determined. METHODS: In the present study, we examined the effect of ovarian steroids, administered at levels that occur during human pregnancy followed by rapid withdrawal to simulate postpartum conditions, on behavior and gene expression in the rat. RESULTS: The results of behavioral testing reveal that the hormone-simulated postpartum treatment results in the development of a phenotype relevant to PPD, including vulnerability for helplessness, increased anxiety, and aggression. Real-time quantitative polymerase chain reaction (PCR) demonstrated transient regulation of several genes, including Ca(2+)/calmodulin-dependent protein kinase II (CAMKII), serotonin transporter (SERT), myocyte enhancer factor 2A (MEF2A), brain-derived neurotrophic factor (BDNF), gamma-aminobutyric acid type A receptor alpha 4 (GABAARA4), mothers against decapentaplegic homolog 4 (SMAD4), and aquaporin 4 (AQP4) that could underlie these behavioral effects. CONCLUSIONS: These studies provide an improved understanding of the effects of withdrawal from high doses of ovarian hormones on behavior and gene expression changes in the brain that could contribute to the pathophysiology of PPD.
BACKGROUND: Postpartum depression (PPD) affects approximately 10% to 20% of women during the first 4 weeks of the postpartum period and is characterized by labile mood with prominent anxiety and irritability, insomnia, and depressive mood. During the postpartum period, elevated ovarian hormones abruptly decrease to the early follicular phase levels that are postulated to play a major role in triggering PPD. However, the underlying neurobiological mechanisms that contribute to PPD have not been determined. METHODS: In the present study, we examined the effect of ovarian steroids, administered at levels that occur during human pregnancy followed by rapid withdrawal to simulate postpartum conditions, on behavior and gene expression in the rat. RESULTS: The results of behavioral testing reveal that the hormone-simulated postpartum treatment results in the development of a phenotype relevant to PPD, including vulnerability for helplessness, increased anxiety, and aggression. Real-time quantitative polymerase chain reaction (PCR) demonstrated transient regulation of several genes, including Ca(2+)/calmodulin-dependent protein kinase II (CAMKII), serotonin transporter (SERT), myocyte enhancer factor 2A (MEF2A), brain-derived neurotrophic factor (BDNF), gamma-aminobutyric acid type A receptor alpha 4 (GABAARA4), mothers against decapentaplegic homolog 4 (SMAD4), and aquaporin 4 (AQP4) that could underlie these behavioral effects. CONCLUSIONS: These studies provide an improved understanding of the effects of withdrawal from high doses of ovarian hormones on behavior and gene expression changes in the brain that could contribute to the pathophysiology of PPD.
Authors: Lauren Osborne; Makena Clive; Mary Kimmel; Fiona Gispen; Jerry Guintivano; Tori Brown; Olivia Cox; Jennifer Judy; Samantha Meilman; Aviva Braier; Matthias W Beckmann; Johannes Kornhuber; Peter A Fasching; Fernando Goes; Jennifer L Payne; Elisabeth B Binder; Zachary Kaminsky Journal: Neuropsychopharmacology Date: 2015-10-27 Impact factor: 7.853