Neurophysiology of Postpartum Depression in an Experimental Model of Pregnancy and Parturition
Condition: Postpartum Depression
MeSH terms: Depression, Postpartum; Depression; Depressive Disorder
Study type: Interventional

Summary: 
      Understanding the neural and biological mechanisms by which reproductive hormones influence
      mood is critically important for public health given that postpartum depression (PPD) is the
      leading cause of morbidity and mortality associated with childbirth and has negative effects
      on infants. Using a hormone-withdrawal challenge to precipitate mood symptoms will improve
      our ability to identify the biological mechanisms underlying both the triggering of and
      susceptibility to depressive disorders in women; and will permit the prediction of those at
      risk for PPD and other reproductive-related mood disorders.
    

Detailed description: 
      Affective disorders, such as PPD and other reproductive-related mood disorders, are common
      and constitute a significant burden for women, children, and society. However, little is
      known about the neurobiological mechanisms underlying depressive disorders in women. The
      long-term goal of this research is to 1) advance our understanding of the biological
      mechanisms underlying both the triggering of and susceptibility to depressive disorders in
      women; and 2) permit the prediction of those at risk for PPD. The objective of the current
      project is to examine whether those with a past episode of PPD (at "high risk" for
      recurrence) show differences in emotional arousal and reward processing domains relative to
      healthy control women (without a history of PPD) under baseline and hormone
      withdrawal-precipitated conditions. The central hypothesis is that reproductive hormone
      changes are associated with dysregulation of the neural circuits underlying emotional arousal
      and reward processing and consequent depressive symptoms in high-risk women. The rationale
      for the proposed study is that employing a scaled down model of puerperal hormonal events in
      high-risk women permits the identification of a group of individuals homogeneous for
      reproductive related affective dysfunction and, hence, the best opportunity for disentangling
      the specific changes in brain function due to reproductive hormones from those accompanying
      reproductive hormone-precipitated affective dysfunction. Moreover, identifying a
      neurophysiologic biomarker for hormone-related affective dysfunction provides a clear pathway
      for examining mechanisms of susceptibility to affective dysfunction across disorders. The
      investigators plan to accomplish the objectives of this application by pursuing the following
      specific aims: 1) to assess the effects of simulated postpartum reproductive hormone
      withdrawal, compared to baseline, on corticolimbic circuit activation in high-risk and
      control women; and 2) to examine the effects of reproductive hormone withdrawal, compared to
      baseline, on reward circuit activation in high-risk and control women. An additional
      exploratory aim is to identify a neural biomarker, characterized by corticolimbic and reward
      circuit dysfunction, that can be used to predict the onset of PPD. The proposed study
      involves experimentally manipulating reproductive hormones in euthymic women to create a
      scaled down version of the changes that occur at the puerperium. This endocrine manipulation
      paradigm will be used to examine the neurocircuitry underlying the regulation of affect and
      reward processing under baseline and hormone withdrawal-precipitated conditions among women
      who are expected to experience hormone-related affective dysregulation (n=15) and controls
      (n=15). In short, the investigators expect that relative to baseline, high-risk women will
      show greater dysregulation in neural circuits responsible for emotion processing and reward
      processing during hormone withdrawal than low-risk control women. The expected outcome of
      this research is the identification of neural circuits underlying both the susceptibility to
      and mediation of hormone-related affective dysfunction. Understanding these neurobiological
      mechanisms will subsequently improve the ability to identify those at risk for PPD, which may
      strengthen prevention efforts and ultimately prevent the deleterious effects of maternal
      depression on offspring.
    

Intervention name(s): Leuprolide Acetate; Micronized estradiol; Progesterone
Intervention type(s): Drug; Drug; Drug
Intervention description(s): All subjects will receive one IM injection (3.75 mg) each month for four months.; All participants will receive micronized estradiol daily for eight weeks. Estradiol will be started at a dose of 4 mg/day and increased progressively up to 10 mg/day.; All subjects will receive micronized progesterone daily for eight weeks. Progesterone will be started at 400 mg/day and increased progressively up to 800 mg/day.
Other intervention name(s): Lupron; Estrace; Micronized progesterone
Intervention MeSH terms: Leuprolide; Estradiol; Progesterone
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science