Neurophysiology of Postpartum Depression in an Experimental Model of Pregnancy and Parturition
2 other identifiers
interventional
36
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for not_applicable
Started Aug 2013
Typical duration for not_applicable
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 13, 2012
CompletedFirst Posted
Study publicly available on registry
January 8, 2013
CompletedStudy Start
First participant enrolled
August 1, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 13, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
October 13, 2016
CompletedResults Posted
Study results publicly available
October 17, 2017
CompletedNovember 20, 2017
February 1, 2017
3.2 years
November 13, 2012
September 15, 2017
October 17, 2017
Conditions
Outcome Measures
Primary Outcomes (1)
Blood-oxygen-level-dependent (BOLD) Response During Functional Magnetic Resonance Imaging (fMRI) z Statistic
The primary outcome measure was functional magnetic resonance imaging (fMRI) data collected during a Monetary Incentive Delay (MID) Task. The BOLD response was examined within the nucleus accumbens, a brain region that responds to monetary rewards. The z statistic represents the maximum contrast between win versus non-win outcomes during the MID task in the nucleus accumbens, averaged across the participants in each group. The mean BOLD response ranged from z=1.7 to 2.3; higher z scores indicate greater activation of the nucleus accumbens during reward. Individual z scores were generated using the Oxford Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB) software library (FSL), which is a library of brain imaging analysis tools for fMRI.
baseline and hormone withdrawal
Secondary Outcomes (1)
Change in Inventory of Depression and Anxiety Symptoms (IDAS) Dysphoria Score
Assessed at baseline and post-treatment
Study Arms (2)
Women with Postpartum Depression (PPD)
EXPERIMENTAL4 monthly (intramuscular) IM injections of leuprolide acetate (Lupron) 3.75 mg; micronized estradiol will be started at a dose of 4 mg/day and increased progressively up to 10 mg/day; progesterone will be started at 400 mg/day and increased progressively up to 800 mg/day. Participants will also receive placebo.
Women without any psychiatric history (Control)
EXPERIMENTAL4 monthly (intramuscular) IM injections of leuprolide acetate (Lupron) 3.75 mg; micronized estradiol will be started at a dose of 4 mg/day and increased progressively up to 10 mg/day; progesterone will be started at 400 mg/day and increased progressively up to 800 mg/day. Participants will also receive placebo.
Interventions
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.
Eligibility Criteria
You may qualify if:
- Group 1: Women with a history of PPD
- A history of a major depression episode that occurred within two months of childbirth (as determined by a SCID interview) and remitted at least one year prior to enrollment in the study;
- has been well for a minimum of one year;
- a regular menstrual cycle for at least three months;
- age 22-50;
- not pregnant, not lactating and in good medical health;
- medication free (not including birth control pills; participants may opt to temporarily discontinue birth control pills to participate);
- no history of puerperal suicide attempts or psychotic episodes requiring hospitalization.
- Group 2: Healthy Controls
- A structured clinical interview (SCID) will be administered to all women prior to study entry. Any woman with a current axis I psychiatric diagnosis will be excluded from participating in this protocol.
You may not qualify if:
- Patients will not be permitted to enter this protocol if they have important clinical or laboratory abnormalities including any of the following:
- current axis I psychiatric diagnosis
- endometriosis;
- undiagnosed enlargement of the ovaries;
- liver disease;
- breast cancer;
- a history of blood clots in the legs or lungs;
- undiagnosed vaginal bleeding;
- porphyria;
- diabetes mellitus;
- malignant melanoma;
- gallbladder or pancreatic disease;
- heart or kidney disease;
- cerebrovascular disease (stroke);
- cigarette smoking;
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of North Carolina, Chapel Hilllead
- Foundation of Hope, North Carolinacollaborator
- North Carolina Translational and Clinical Sciences Institutecollaborator
- National Institutes of Health (NIH)collaborator
- National Alliance for Research on Schizophrenia and Depressioncollaborator
- National Institute of Mental Health (NIMH)collaborator
Study Sites (1)
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599-7175, United States
Related Publications (3)
Bloch M, Schmidt PJ, Danaceau M, Murphy J, Nieman L, Rubinow DR. Effects of gonadal steroids in women with a history of postpartum depression. Am J Psychiatry. 2000 Jun;157(6):924-30. doi: 10.1176/appi.ajp.157.6.924.
PMID: 10831472BACKGROUNDRudzinskas SA, Mazzu MA, Schiller CE, Meltzer-Brody S, Rubinow DR, Schmidt PJ, Goldman D. Divergent Transcriptomic Effects of Allopregnanolone in Postpartum Depression. Genes (Basel). 2023 Jun 8;14(6):1234. doi: 10.3390/genes14061234.
PMID: 37372414DERIVEDRudzinskas SA, Goff AC, Mazzu MA, Schiller CE, Meltzer-Brody S, Rubinow DR, Schmidt PJ, Goldman D. Intrinsically dysregulated cellular stress signaling genes and gene networks in postpartum depression. Mol Psychiatry. 2023 Jul;28(7):3023-3032. doi: 10.1038/s41380-023-01985-5. Epub 2023 Feb 13.
PMID: 36782063DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Crystal Schiller
- Organization
- University of North Carolina at Chapel Hill
Study Officials
- PRINCIPAL INVESTIGATOR
Crystal E Schiller, Ph.D.
University of North Carolina, Chapel Hill
- PRINCIPAL INVESTIGATOR
David R Rubinow, M.D.
University of North Carolina, Chapel Hill
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- BASIC SCIENCE
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 13, 2012
First Posted
January 8, 2013
Study Start
August 1, 2013
Primary Completion
October 13, 2016
Study Completion
October 13, 2016
Last Updated
November 20, 2017
Results First Posted
October 17, 2017
Record last verified: 2017-02
Data Sharing
- IPD Sharing
- Will not share