The Candidate proposes this Mentored Patient-Oriented Research Career Award application to provide her with expert training and mentorship to support her development as an independent clinician scientist in the field of perinatal mental health. The long-term career goals of the Candidate are 1) To establish a program of research focusing on the treatment and predictors of treatment response for major psychiatric disorders in pregnant women; 2) To develop the translational aspects of her clinical research program by fully incorporating a sophisticated understanding of the neuroendocrinology of pregnancy; 3) To develop her skills as an independent investigator, educator and mentor focusing on patient-oriented research at the interface between psychiatry and obstetrics and gynecology. In order to meet these goals, the application provides a detailed description of 5 training modules including 1) Research projects, 2) Laboratory training, 3) Didactic course work including completion of a Masters in Translational Research, 4) Individual tutorials, and 5) Extramural supervision. The development of researchers focused on the treatment of depression during pregnancy has important ramifications for mother and her offspring. Depression during pregnancy affects approximately 13% of pregnant women making it a national health issue of vital importance. There is mounting evidence that antidepressants may adversely affect pregnancy outcome and fetal health. Psychotherapy is a first-line treatment for this special population but other options must be studied as no treatment will work in all patients. Repetitive transcranial magnetic stimulation (rTMS) is a FDA-approved device for the non-pharmacologic treatment of depression in adults. It is critical that rTMS, as a non-pharmacologic treatment, be evaluated for the treatment of major depressive disorder (MDD) during pregnancy. Our pilot data suggests this is a feasible and safe treatment for 2nd and 3rd trimester pregnant women with depression. Our pilot data also suggests that the device parameters may be affected by the pregnant state which if not addressed could affect efficacy. We propose a double-blind, placebo-controlled clinical trial using 1 Hz active versus sham rTMS of the right dorsolateral prefrontal cortex (DLPFC) of 66 pregnant women with moderate to severe major depressive disorder (MDD). We expect a significant decrease in depression scores after 20 sessions in the active group compared to the sham group. In addition, we will evaluate the device power output necessary to obtain the resting motor threshold in pregnant subjects compared to 16 age-matched, non-pregnant, healthy women in the luteal phase of the menstrual cycle. Finally, to better understand the mechanism by which rTMS may be effective for the treatment of depression during pregnancy, we will measure maternal serum brain derived neurotrophic factor (BDNF) and correlate it with levels of estradiol, progesterone, allopregnanolone, oxytocin and corticotrophin-releasing hormone (CRH) levels pre and post-rTMS. This award will solidly prepare the Candidate to pursue further research funding and the development of non-pharmacological, somatic treatments for pregnant women suffering from mental illness.

Public Health Relevance

Depression during pregnancy is a common illness that affects both mother and child. Many women prefer not to take antidepressant medications during pregnancy. We will study a non- medication, somatic alternative called repetitive transcranial magnetic stimulation (rTMS) which could provide pregnant women with depression an alternative treatment option.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Mentored Patient-Oriented Research Career Development Award (K23)
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Study Section
Interventions Committee for Adult Disorders (ITVA)
Program Officer
Chavez, Mark
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University of Pennsylvania
Schools of Medicine
United States
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Hantsoo, Liisa; Podcasy, Jessica; Sammel, Mary et al. (2017) Pregnancy and the Acceptability of Computer-Based Versus Traditional Mental Health Treatments. J Womens Health (Larchmt) 26:1106-1113
Morrison, Kathleen E; Epperson, C Neill; Sammel, Mary D et al. (2017) Preadolescent Adversity Programs a Disrupted Maternal Stress Reactivity in Humans and Mice. Biol Psychiatry 81:693-701
Kim, Deborah R; Pinheiro, Emily; Luther, James F et al. (2016) Is third trimester serotonin reuptake inhibitor use associated with postpartum hemorrhage? J Psychiatr Res 73:79-85
Ewing, Grace; Tatarchuk, Yekaterina; Appleby, Dina et al. (2015) Placental transfer of antidepressant medications: implications for postnatal adaptation syndrome. Clin Pharmacokinet 54:359-70
Anderson, Eleanor A; Kim, Deborah R (2015) Psychiatric consultation to the postpartum mother. Curr Psychiatry Rep 17:561
Kim, Deborah R; Bale, Tracy L; Epperson, C Neill (2015) Prenatal programming of mental illness: current understanding of relationship and mechanisms. Curr Psychiatry Rep 17:5
Kim, Deborah R; Hantsoo, Liisa; Thase, Michael E et al. (2014) Computer-assisted cognitive behavioral therapy for pregnant women with major depressive disorder. J Womens Health (Larchmt) 23:842-8
Kim, Deborah R; Epperson, C Neill; Weiss, Amy R et al. (2014) Pharmacotherapy of postpartum depression: an update. Expert Opin Pharmacother 15:1223-34
Kim, Deborah Rubin; Wang, Eileen (2014) Prevention of supine hypotensive syndrome in pregnant women treated with transcranial magnetic stimulation. Psychiatry Res 218:247-8
Hantsoo, Liisa; Epperson, C Neill; Thase, Michael E et al. (2013) Antepartum depression: treatment with computer-assisted cognitive-behavioral therapy. Am J Psychiatry 170:929-30

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