Post Partum DepressionNCT03638687
Neuroimaging Epigenetics of Prospective Postpartum Depression Biomarkers
An observational study of Post Partum Depression and Bipolar Disorder, run by Johns Hopkins University at 1 site in United States.
Trial summary
Through a recent cross species translational experiment, researchers have identified a set of epigenetic marks capable of predicting postpartum depression with greater than 85% accuracy. Read more about this study
- Who is it for?
- Ages 18 to 65 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Post Partum Depression, Bipolar Disorder
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- May 2014to Aug 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Study population: The study population includes women 18 years or older, pregnant with a singleton pregnancy, and with or without a history of a mood disorder. Participants may take psychiatric medications, however they may not be currently suicidal, psychiatrically unstable, or be currently abusing substances.
Who may be able to join
- pregnant women 18 or older with singleton pregnancy
- with or without history of a mood disorder
- may use psychiatric or Over-the-counter (OTC) medications
- may have experienced preterm labor or delivery
- must be willing to undergo repeated MRI scans (for wave 2)
Who cannot join
- current active suicidal ideation
- medical or psychiatric instability
- active substance abuse or dependence in last 90 days
- any significant neurologic disease (wave 2)
- presence of known infection, infarction, lesion in critical memory structures of brain (wave 2)
- pace maker, aneurysm clips, artificial heart valve, ear implants, metal fragments (wave 2)
- high risk pregnancy indications i.e. preeclampsia, genetic anomalies, women with HIV, Lupus, Irritable Bowel Syndrome (IBS) (wave 2)
- implanted Intra-uterine devices (IUDs) or birth control prior to 6 weeks postpartum (wave 2)
Trial locations and contacts
1 site in 1 country.
United States1 site
Johns Hopkins East Baltimore Medical Campus
Baltimore, Maryland, 21205
About this study
Through a recent cross species translational experiment, researchers have identified a set of epigenetic marks capable of predicting postpartum depression with greater than 85% accuracy. The researchers are looking to identify a group of women from both the general population and those with a history of mood disorders who are at risk for postpartum depression and obtain brain imaging data at a postpartum time period prior to the onset of depressive symptoms and compare it with those obtained during depressive episodes. The researchers will also evaluate the efficacy of postpartum depression biomarker prediction.
Read the detailed description
Postpartum depression (PPD) occurs in approximately 10-18% of women from the general population, affecting ~400,000 to 800,000 women each year. PPD results in significant morbidity to both mother and child, with offspring risks including low self-esteem, low intellectual skills, child abuse, and infanticide. PPD occurs within four weeks following parturition according to Diagnostic and Statistical Manual (DSM)-IV criteria and follows a dramatic drop in the circulating levels of estradiol (E2) and progesterone (P4). While PPD risk is not predicted by serum levels of gonadal hormones in humans, numerous studies suggest that risk to PPD is mediated by hormonal sensitivity. Recently, the investigators demonstrated that women at risk to PPD demonstrate an increased sensitivity to E2 mediated DNA methylation reprogramming at hippocampally relevant genes and identified two biomarkers, Tetratricopeptide repeat protein 9B (TTC9B) and heterochromatin protein 1 binding protein 3 (HP1BP3) that appeared functionally related to modulating neuroplasticity and which were predictive of PPD with 82-96% accuracy. Given that peripherally measurable epigenetic marks in genes implicated in hormone related neuroplastic changes may underlie risk to PPD, it is logical to next investigate neuroconnectivity alterations occurring longitudinally in the postpartum population at risk for PPD. The study is divided into two waves; in wave 1, the researchers will draw a tube of blood to be used as a biomarker screening to identify those at risk for PPD and matched controls, who will be asked to enter wave 2 of the study. In wave 2, women will undergo neuroimaging at weeks 2 and 6 postpartum in hopes to gather a neural signature of PPD prior to the onset of symptoms and while experiencing the symptoms. Additionally, data on a variety of candidate moderators of depression during or after pregnancy will be collected at each visit. This includes history of premenstrual symptoms, use of oral contraceptives, use of hormonal treatments to promote pregnancy and psychiatric history during previous pregnancies and the postpartum. Several measures of mood symptoms and anxiety symptoms will be administered including: Edinburgh Postnatal Depression Rating Scale (EPDS) which measures depressive symptoms in pregnant and postpartum mothers, the Young Mania Rating Scale, which rates manic and hypomanic symptoms, and the State Trait Anxiety Inventory, Perinatal Anxiety Scale, and the Penn State Worry questionnaire which measure anxiety symptoms. The Pittsburgh Sleep Quality Index scale will be administered at every visit to assess the role of sleep in the relapse of depression in the mothers. Two scales designed to measure stress will be administered to allow examination of its potential role in Major Depressive Disorder (MDD) relapse. The Recent Life Changes Scale, which measures stressful life events, will be administered at the Screening, 3rd trimester and 6 week visits. The Perceived Stress Scale which provides a subjective rating of the stress of will be administered at every visit. The investigators will also administer measures of childhood trauma, and note demographic information, medication usage, clinical history (e.g. number of hospitalizations, medication trials, etc.) and birth outcomes. These measures will be used in future exploratory analyses of potential moderators of epigenetic changes seen during and after pregnancy.
- Conditions
- Post Partum Depression, Bipolar Disorder
- Keywords
- Pregnancy, Postpartum
- Medical subject headings
- Depression, Postpartum, Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| History, Yes PPD | Participants may be asked to undergo repeated neuroimaging scans. No intervention will be administered, all participants will receive routine care during the study. | |
| No History, No PPD | Participants may be asked to undergo repeated neuroimaging scans. No intervention will be administered, all participants will receive routine care during the study. | |
| History, No PPD | Participants may be asked to undergo repeated neuroimaging scans. No intervention will be administered, all participants will receive routine care during the study. | |
| No History, Yes PPD | Participants may be asked to undergo repeated neuroimaging scans. No intervention will be administered, all participants will receive routine care during the study. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Epigenetic Analysis
One blood sample will be drawn in the third trimester and the epigenetic information obtained will be put into a model of prediction for postpartum depression.
Measured: At week 33 of pregnancy
Secondary outcomes (1)
Brain Imaging
An functional MRI (fMRI) of hippocampal subregions and surrounding structures at a postpartum time period prior to the onset of depressive symptoms (2 weeks postpartum) and compared with those obtained during depressive episodes (6 weeks postpartum) to assess differences in functioning.
Measured: 4 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2018
- Study startMay 2014
- Primary completionOct 2019
- Study completionAug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (58)Papers the sponsor has linked to this study.
- Other trials for Post Partum DepressionStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- Zachary A Kaminsky, Ph.D., Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03638687
- Sponsor's protocol ID
- IRB00038271
- Other IDs
- R01MH104262
- Status last verified
- Sep 2020
- First submitted
- 16 Aug 2018
- Last updated
- 22 Sep 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
O'Hara MW. Postpartum depression: what we know. J Clin Psychol. 2009 Dec;65(12):1258-69. doi: 10.1002/jclp.20644.
PubMed 19827112Soufia M, Aoun J, Gorsane MA, Krebs MO. [SSRIs and pregnancy: a review of the literature]. Encephale. 2010 Dec;36(6):513-6. doi: 10.1016/j.encep.2010.02.003. Epub 2010 Apr 3. French.
PubMed 21130237Field T. Prenatal depression effects on early development: a review. Infant Behav Dev. 2011 Feb;34(1):1-14. doi: 10.1016/j.infbeh.2010.09.008.
PubMed 20970195Breese McCoy SJ. Postpartum depression: an essential overview for the practitioner. South Med J. 2011 Feb;104(2):128-32. doi: 10.1097/SMJ.0b013e318200c221.
PubMed 21206417Cuijpers P, Brannmark JG, van Straten A. Psychological treatment of postpartum depression: a meta-analysis. J Clin Psychol. 2008 Jan;64(1):103-18. doi: 10.1002/jclp.20432.
PubMed 18161036Hirst KP, Moutier CY. Postpartum major depression. Am Fam Physician. 2010 Oct 15;82(8):926-33.
PubMed 20949886Marcus SM. Depression during pregnancy: rates, risks and consequences--Motherisk Update 2008. Can J Clin Pharmacol. 2009 Winter;16(1):e15-22. Epub 2009 Jan 22.
PubMed 19164843Studd JW. A guide to the treatment of depression in women by estrogens. Climacteric. 2011 Dec;14(6):637-42. doi: 10.3109/13697137.2011.609285. Epub 2011 Aug 31.
PubMed 21878053Bloch 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.
PubMed 10831472Bloch M, Rubinow DR, Schmidt PJ, Lotsikas A, Chrousos GP, Cizza G. Cortisol response to ovine corticotropin-releasing hormone in a model of pregnancy and parturition in euthymic women with and without a history of postpartum depression. J Clin Endocrinol Metab. 2005 Feb;90(2):695-9. doi: 10.1210/jc.2004-1388. Epub 2004 Nov 16.
PubMed 15546899Guintivano J, Arad M, Gould TD, Payne JL, Kaminsky ZA. Antenatal prediction of postpartum depression with blood DNA methylation biomarkers. Mol Psychiatry. 2014 May;19(5):560-7. doi: 10.1038/mp.2013.62. Epub 2013 May 21.
PubMed 23689534Kimmel M, Kaminsky Z, Payne JL. Biomarker or pathophysiology? The role of DNA methylation in postpartum depression. Epigenomics. 2013;5(5):473-5. doi: 10.2217/epi.13.51. No abstract available.
PubMed 24059792Walf AA, Koonce CJ, Frye CA. Estradiol or diarylpropionitrile decrease anxiety-like behavior of wildtype, but not estrogen receptor beta knockout, mice. Behav Neurosci. 2008 Oct;122(5):974-81. doi: 10.1037/a0012749.
PubMed 18823154Osterlund MK, Witt MR, Gustafsson JA. Estrogen action in mood and neurodegenerative disorders: estrogenic compounds with selective properties-the next generation of therapeutics. Endocrine. 2005 Dec;28(3):235-42. doi: 10.1385/ENDO:28:3:235.
PubMed 16388113Lund TD, Rovis T, Chung WC, Handa RJ. Novel actions of estrogen receptor-beta on anxiety-related behaviors. Endocrinology. 2005 Feb;146(2):797-807. doi: 10.1210/en.2004-1158. Epub 2004 Oct 28.
PubMed 15514081
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neuroimaging Epigenetics of Prospective Postpartum Depression Biomarkers
- ClinicalTrials.gov ID
- NCT03638687
- Acronym / sponsor ID
- IRB00038271
- Conditions
- Post Partum Depression, Bipolar Disorder
- Keywords
- Pregnancy, Postpartum
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- May 2014 (actual)
- Primary completion
- Oct 2019 (actual)
- Study completion
- Aug 2020 (actual)
- First posted
- 20 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Through a recent cross species translational experiment, researchers have identified a set of epigenetic marks capable of predicting postpartum depression with greater than 85% accuracy. The researchers are looking to identify a group of women from both the general population and those with a history of mood disorders who are at risk for postpartum depression and obtain brain imaging data at a postpartum time period prior to the onset of depressive symptoms and compare it with those obtained during depressive episodes. The researchers will also evaluate the efficacy of postpartum depression biomarker prediction.
Detailed description
Postpartum depression (PPD) occurs in approximately 10-18% of women from the general population, affecting ~400,000 to 800,000 women each year. PPD results in significant morbidity to both mother and child, with offspring risks including low self-esteem, low intellectual skills, child abuse, and infanticide. PPD occurs within four weeks following parturition according to Diagnostic and Statistical Manual (DSM)-IV criteria and follows a dramatic drop in the circulating levels of estradiol (E2) and progesterone (P4). While PPD risk is not predicted by serum levels of gonadal hormones in humans, numerous studies suggest that risk to PPD is mediated by hormonal sensitivity. Recently, the investigators demonstrated that women at risk to PPD demonstrate an increased sensitivity to E2 mediated DNA methylation reprogramming at hippocampally relevant genes and identified two biomarkers, Tetratricopeptide repeat protein 9B (TTC9B) and heterochromatin protein 1 binding protein 3 (HP1BP3) that appeared functionally related to modulating neuroplasticity and which were predictive of PPD with 82-96% accuracy. Given that peripherally measurable epigenetic marks in genes implicated in hormone related neuroplastic changes may underlie risk to PPD, it is logical to next investigate neuroconnectivity alterations occurring longitudinally in the postpartum population at risk for PPD. The study is divided into two waves; in wave 1, the researchers will draw a tube of blood to be used as a biomarker screening to identify those at risk for PPD and matched controls, who will be asked to enter wave 2 of the study. In wave 2, women will undergo neuroimaging at weeks 2 and 6 postpartum in hopes to gather a neural signature of PPD prior to the onset of symptoms and while experiencing the symptoms. Additionally, data on a variety of candidate moderators of depression during or after pregnancy will be collected at each visit. This includes history of premenstrual symptoms, use of oral contraceptives, use of hormonal treatments to promote pregnancy and psychiatric history during previous pregnancies and the postpartum. Several measures of mood symptoms and anxiety symptoms will be administered including: Edinburgh Postnatal Depression Rating Scale (EPDS) which measures depressive symptoms in pregnant and postpartum mothers, the Young Mania Rating Scale, which rates manic and hypomanic symptoms, and the State Trait Anxiety Inventory, Perinatal Anxiety Scale, and the Penn State Worry questionnaire which measure anxiety symptoms. The Pittsburgh Sleep Quality Index scale will be administered at every visit to assess the role of sleep in the relapse of depression in the mothers. Two scales designed to measure stress will be administered to allow examination of its potential role in Major Depressive Disorder (MDD) relapse. The Recent Life Changes Scale, which measures stressful life events, will be administered at the Screening, 3rd trimester and 6 week visits. The Perceived Stress Scale which provides a subjective rating of the stress of will be administered at every visit. The investigators will also administer measures of childhood trauma, and note demographic information, medication usage, clinical history (e.g. number of hospitalizations, medication trials, etc.) and birth outcomes. These measures will be used in future exploratory analyses of potential moderators of epigenetic changes seen during and after pregnancy.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| History, Yes PPD | – | –Participants may be asked to undergo repeated neuroimaging scans. No intervention will be administered, all participants will receive routine care during the study. |
| No History, No PPD | – | –Participants may be asked to undergo repeated neuroimaging scans. No intervention will be administered, all participants will receive routine care during the study. |
| History, No PPD | – | –Participants may be asked to undergo repeated neuroimaging scans. No intervention will be administered, all participants will receive routine care during the study. |
| No History, Yes PPD | – | –Participants may be asked to undergo repeated neuroimaging scans. No intervention will be administered, all participants will receive routine care during the study. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- The study population includes women 18 years or older, pregnant with a singleton pregnancy, and with or without a history of a mood disorder. Participants may take psychiatric medications, however they may not be currently suicidal, psychiatrically unstable, or be currently abusing substances.
Key inclusion criteria (5 listed)
- pregnant women 18 or older with singleton pregnancy
- with or without history of a mood disorder
- may use psychiatric or Over-the-counter (OTC) medications
- may have experienced preterm labor or delivery
- must be willing to undergo repeated MRI scans (for wave 2)
Key exclusion criteria (8 listed)
- current active suicidal ideation
- medical or psychiatric instability
- active substance abuse or dependence in last 90 days
- any significant neurologic disease (wave 2)
- presence of known infection, infarction, lesion in critical memory structures of brain (wave 2)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Epigenetic Analysis
Time frame: At week 33 of pregnancy
One blood sample will be drawn in the third trimester and the epigenetic information obtained will be put into a model of prediction for postpartum depression.
1 secondary outcome
Brain Imaging
Time frame: 4 Weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2020.
- Background: PubMed 19827112O'Hara MW. Postpartum depression: what we know. J Clin Psychol. 2009 Dec;65(12):1258-69. doi: 10.1002/jclp.20644.
- Background: PubMed 21130237Soufia M, Aoun J, Gorsane MA, Krebs MO. [SSRIs and pregnancy: a review of the literature]. Encephale. 2010 Dec;36(6):513-6. doi: 10.1016/j.encep.2010.02.003. Epub 2010 Apr 3. French.
- Background: PubMed 20970195Field T. Prenatal depression effects on early development: a review. Infant Behav Dev. 2011 Feb;34(1):1-14. doi: 10.1016/j.infbeh.2010.09.008.
- Background: PubMed 21206417Breese McCoy SJ. Postpartum depression: an essential overview for the practitioner. South Med J. 2011 Feb;104(2):128-32. doi: 10.1097/SMJ.0b013e318200c221.
- Background: PubMed 18161036Cuijpers P, Brannmark JG, van Straten A. Psychological treatment of postpartum depression: a meta-analysis. J Clin Psychol. 2008 Jan;64(1):103-18. doi: 10.1002/jclp.20432.
- Background: PubMed 20949886Hirst KP, Moutier CY. Postpartum major depression. Am Fam Physician. 2010 Oct 15;82(8):926-33.
- Background: PubMed 19164843Marcus SM. Depression during pregnancy: rates, risks and consequences--Motherisk Update 2008. Can J Clin Pharmacol. 2009 Winter;16(1):e15-22. Epub 2009 Jan 22.
- Background: PubMed 21878053Studd JW. A guide to the treatment of depression in women by estrogens. Climacteric. 2011 Dec;14(6):637-42. doi: 10.3109/13697137.2011.609285. Epub 2011 Aug 31.
- Background: PubMed 10831472Bloch 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.
- Background: PubMed 15546899Bloch M, Rubinow DR, Schmidt PJ, Lotsikas A, Chrousos GP, Cizza G. Cortisol response to ovine corticotropin-releasing hormone in a model of pregnancy and parturition in euthymic women with and without a history of postpartum depression. J Clin Endocrinol Metab. 2005 Feb;90(2):695-9. doi: 10.1210/jc.2004-1388. Epub 2004 Nov 16.
- Background: PubMed 23689534Guintivano J, Arad M, Gould TD, Payne JL, Kaminsky ZA. Antenatal prediction of postpartum depression with blood DNA methylation biomarkers. Mol Psychiatry. 2014 May;19(5):560-7. doi: 10.1038/mp.2013.62. Epub 2013 May 21.
- Background: PubMed 24059792Kimmel M, Kaminsky Z, Payne JL. Biomarker or pathophysiology? The role of DNA methylation in postpartum depression. Epigenomics. 2013;5(5):473-5. doi: 10.2217/epi.13.51. No abstract available.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Zachary A Kaminsky, Ph.D. principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Post Partum Depression and Bipolar Disorder, run by Johns Hopkins University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Epigenetic Analysis (time frame: At week 33 of pregnancy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03638687, which also lists 58 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2020.