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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03638687
Other study ID # IRB00038271
Secondary ID R01MH104262
Status Completed
Phase
First received
Last updated
Start date May 2014
Est. completion date August 2020

Study information

Verified date September 2020
Source Johns Hopkins University
Contact n/a
Is FDA regulated No
Health authority
Study type Observational

Clinical 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. 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 80
Est. completion date August 2020
Est. primary completion date October 2019
Accepts healthy volunteers Accepts Healthy Volunteers
Gender Female
Age group 18 Years to 65 Years
Eligibility Inclusion Criteria:

- 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)

Exclusion Criteria:

- 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)

Study Design


Locations

Country Name City State
United States Johns Hopkins East Baltimore Medical Campus Baltimore Maryland

Sponsors (2)

Lead Sponsor Collaborator
Johns Hopkins University National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

References & Publications (58)

Amin Z, Epperson CN, Constable RT, Canli T. Effects of estrogen variation on neural correlates of emotional response inhibition. Neuroimage. 2006 Aug 1;32(1):457-64. Epub 2006 Apr 27. — View Citation

Andréen L, Nyberg S, Turkmen S, van Wingen G, Fernández G, Bäckström T. Sex steroid induced negative mood may be explained by the paradoxical effect mediated by GABAA modulators. Psychoneuroendocrinology. 2009 Sep;34(8):1121-32. doi: 10.1016/j.psyneuen.2009.02.003. Epub 2009 Mar 9. Review. — View Citation

Avants BB, Yushkevich P, Pluta J, Minkoff D, Korczykowski M, Detre J, Gee JC. The optimal template effect in hippocampus studies of diseased populations. Neuroimage. 2010 Feb 1;49(3):2457-66. doi: 10.1016/j.neuroimage.2009.09.062. Epub 2009 Oct 8. — View Citation

Bäckström T, Haage D, Löfgren M, Johansson IM, Strömberg J, Nyberg S, Andréen L, Ossewaarde L, van Wingen GA, Turkmen S, Bengtsson SK. Paradoxical effects of GABA-A modulators may explain sex steroid induced negative mood symptoms in some persons. Neuroscience. 2011 Sep 15;191:46-54. doi: 10.1016/j.neuroscience.2011.03.061. Epub 2011 May 13. Review. — View Citation

Bakker A, Kirwan CB, Miller M, Stark CE. Pattern separation in the human hippocampal CA3 and dentate gyrus. Science. 2008 Mar 21;319(5870):1640-2. doi: 10.1126/science.1152882. — View Citation

Bakker A, Krauss GL, Albert MS, Speck CL, Jones LR, Stark CE, Yassa MA, Bassett SS, Shelton AL, Gallagher M. Reduction of hippocampal hyperactivity improves cognition in amnestic mild cognitive impairment. Neuron. 2012 May 10;74(3):467-74. doi: 10.1016/j.neuron.2012.03.023. — View Citation

Bannbers E, Gingnell M, Engman J, Morell A, Sylvén S, Skalkidou A, Kask K, Bäckström T, Wikström J, Poromaa IS. Prefrontal activity during response inhibition decreases over time in the postpartum period. Behav Brain Res. 2013 Mar 15;241:132-8. doi: 10.1016/j.bbr.2012.12.003. Epub 2012 Dec 10. — View Citation

Barrett J, Wonch KE, Gonzalez A, Ali N, Steiner M, Hall GB, Fleming AS. Maternal affect and quality of parenting experiences are related to amygdala response to infant faces. Soc Neurosci. 2012;7(3):252-68. doi: 10.1080/17470919.2011.609907. Epub 2011 Sep 26. — View Citation

Bennett MR. The prefrontal-limbic network in depression: Modulation by hypothalamus, basal ganglia and midbrain. Prog Neurobiol. 2011 Apr;93(4):468-87. doi: 10.1016/j.pneurobio.2011.01.006. Epub 2011 Feb 22. Review. — View Citation

Bloch 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. Epub 2004 Nov 16. — View Citation

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. — View Citation

Breese McCoy SJ. Postpartum depression: an essential overview for the practitioner. South Med J. 2011 Feb;104(2):128-32. doi: 10.1097/SMJ.0b013e318200c221. Review. — View Citation

Bunevicius R, Kusminskas L, Mickuviene N, Bunevicius A, Pedersen CA, Pop VJ. Depressive disorder and thyroid axis functioning during pregnancy. World J Biol Psychiatry. 2009;10(4):324-9. doi: 10.3109/15622970903144038. — View Citation

Cohen S, Kamarck T, Mermelstein R. A global measure of perceived stress. J Health Soc Behav. 1983 Dec;24(4):385-96. — View Citation

Costa PT Jr, McCrae RR. Domains and facets: hierarchical personality assessment using the revised NEO personality inventory. J Pers Assess. 1995 Feb;64(1):21-50. — View Citation

Cox JL, Holden JM, Sagovsky R. Detection of postnatal depression. Development of the 10-item Edinburgh Postnatal Depression Scale. Br J Psychiatry. 1987 Jun;150:782-6. — View Citation

Cuijpers P, Brännmark JG, van Straten A. Psychological treatment of postpartum depression: a meta-analysis. J Clin Psychol. 2008 Jan;64(1):103-18. — View Citation

Deligiannidis KM, Sikoglu EM, Shaffer SA, Frederick B, Svenson AE, Kopoyan A, Kosma CA, Rothschild AJ, Moore CM. GABAergic neuroactive steroids and resting-state functional connectivity in postpartum depression: a preliminary study. J Psychiatr Res. 2013 Jun;47(6):816-28. doi: 10.1016/j.jpsychires.2013.02.010. Epub 2013 Mar 15. — View Citation

Fester L, Labitzke J, Hinz R, Behem C, Horling K, Bernhard T, Bader MI, Vollmer G, Rune GM. Estradiol responsiveness of synaptopodin in hippocampal neurons is mediated by estrogen receptor ß. J Steroid Biochem Mol Biol. 2013 Nov;138:455-61. doi: 10.1016/j.jsbmb.2013.09.004. Epub 2013 Sep 25. — View Citation

Field 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. Review. — View Citation

Green AD, Galea LA. Adult hippocampal cell proliferation is suppressed with estrogen withdrawal after a hormone-simulated pregnancy. Horm Behav. 2008 Jun;54(1):203-11. doi: 10.1016/j.yhbeh.2008.02.023. Epub 2008 Mar 12. — View Citation

Guintivano 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. Erratum in: Mol Psychiatry. 2014 May; 19(5):633. — View Citation

Guy, W., Clinical global impression. ECDEU Assessment Manual for Psychopharmacology, Revised. 1976, Rockville, MD: National Institute of Mental Health.

Hirst KP, Moutier CY. Postpartum major depression. Am Fam Physician. 2010 Oct 15;82(8):926-33. Review. — View Citation

Holmes TH, Rahe RH. The Social Readjustment Rating Scale. J Psychosom Res. 1967 Aug;11(2):213-8. — View Citation

Kahn I, Andrews-Hanna JR, Vincent JL, Snyder AZ, Buckner RL. Distinct cortical anatomy linked to subregions of the medial temporal lobe revealed by intrinsic functional connectivity. J Neurophysiol. 2008 Jul;100(1):129-39. doi: 10.1152/jn.00077.2008. Epub 2008 Apr 2. — View Citation

Kimmel 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. — View Citation

Klein A, Andersson J, Ardekani BA, Ashburner J, Avants B, Chiang MC, Christensen GE, Collins DL, Gee J, Hellier P, Song JH, Jenkinson M, Lepage C, Rueckert D, Thompson P, Vercauteren T, Woods RP, Mann JJ, Parsey RV. Evaluation of 14 nonlinear deformation algorithms applied to human brain MRI registration. Neuroimage. 2009 Jul 1;46(3):786-802. doi: 10.1016/j.neuroimage.2008.12.037. Epub 2009 Jan 13. — View Citation

Lacy JW, Yassa MA, Stark SM, Muftuler LT, Stark CE. Distinct pattern separation related transfer functions in human CA3/dentate and CA1 revealed using high-resolution fMRI and variable mnemonic similarity. Learn Mem. 2010 Dec 16;18(1):15-8. doi: 10.1101/lm.1971111. Print 2011 Jan. — View Citation

Laurent HK, Ablow JC. A face a mother could love: depression-related maternal neural responses to infant emotion faces. Soc Neurosci. 2013;8(3):228-39. doi: 10.1080/17470919.2012.762039. Epub 2013 Jan 21. — View Citation

Lee KA. Self-reported sleep disturbances in employed women. Sleep. 1992 Dec;15(6):493-8. — View Citation

Leibenluft E, Yonkers KA. The ties that bind: maternal-infant interactions and the neural circuitry of postpartum depression. Am J Psychiatry. 2010 Nov;167(11):1294-6. doi: 10.1176/appi.ajp.2010.10081159. — View Citation

Lund TD, Rovis T, Chung WC, Handa RJ. Novel actions of estrogen receptor-beta on anxiety-related behaviors. Endocrinology. 2005 Feb;146(2):797-807. Epub 2004 Oct 28. — View Citation

MacLusky NJ, Luine VN, Hajszan T, Leranth C. The 17alpha and 17beta isomers of estradiol both induce rapid spine synapse formation in the CA1 hippocampal subfield of ovariectomized female rats. Endocrinology. 2005 Jan;146(1):287-93. Epub 2004 Oct 14. — View Citation

Magiakou MA, Mastorakos G, Rabin D, Dubbert B, Gold PW, Chrousos GP. Hypothalamic corticotropin-releasing hormone suppression during the postpartum period: implications for the increase in psychiatric manifestations at this time. J Clin Endocrinol Metab. 1996 May;81(5):1912-7. — View Citation

Marcus 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. Review. — View Citation

Moses-Kolko EL, Perlman SB, Wisner KL, James J, Saul AT, Phillips ML. Abnormally reduced dorsomedial prefrontal cortical activity and effective connectivity with amygdala in response to negative emotional faces in postpartum depression. Am J Psychiatry. 2010 Nov;167(11):1373-80. doi: 10.1176/appi.ajp.2010.09081235. Epub 2010 Sep 15. — View Citation

O'Hara MW. Postpartum depression: what we know. J Clin Psychol. 2009 Dec;65(12):1258-69. doi: 10.1002/jclp.20644. — View Citation

Osterlund 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. Review. — View Citation

Pedersen CA, Johnson JL, Silva S, Bunevicius R, Meltzer-Brody S, Hamer RM, Leserman J. Antenatal thyroid correlates of postpartum depression. Psychoneuroendocrinology. 2007 Apr;32(3):235-45. Epub 2007 Mar 7. — View Citation

Pinette MG, Wax JR. The management of depression during pregnancy: a report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists. Obstet Gynecol. 2010 Jan;115(1):188-9. doi: 10.1097/AOG.0b013e3181c8b21d. — View Citation

Silverman ME, Loudon H, Safier M, Protopopescu X, Leiter G, Liu X, Goldstein M. Neural dysfunction in postpartum depression: an fMRI pilot study. CNS Spectr. 2007 Nov;12(11):853-62. — View Citation

Skrundz M, Bolten M, Nast I, Hellhammer DH, Meinlschmidt G. Plasma oxytocin concentration during pregnancy is associated with development of postpartum depression. Neuropsychopharmacology. 2011 Aug;36(9):1886-93. doi: 10.1038/npp.2011.74. Epub 2011 May 11. — View Citation

Soufia 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. Review. French. — View Citation

Spitzer RL, Kroenke K, Williams JB, Löwe B. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006 May 22;166(10):1092-7. — View Citation

Studd 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. Review. — View Citation

Stuebe AM, Grewen K, Pedersen CA, Propper C, Meltzer-Brody S. Failed lactation and perinatal depression: common problems with shared neuroendocrine mechanisms? J Womens Health (Larchmt). 2012 Mar;21(3):264-72. doi: 10.1089/jwh.2011.3083. Epub 2011 Dec 28. — View Citation

Suda S, Segi-Nishida E, Newton SS, Duman RS. A postpartum model in rat: behavioral and gene expression changes induced by ovarian steroid deprivation. Biol Psychiatry. 2008 Aug 15;64(4):311-9. doi: 10.1016/j.biopsych.2008.03.029. Epub 2008 May 8. — View Citation

Tanaka M, Sokabe M. Bidirectional modulatory effect of 17ß-estradiol on NMDA receptors via ERa and ERß in the dentate gyrus of juvenile male rats. Neuropharmacology. 2013 Dec;75:262-73. doi: 10.1016/j.neuropharm.2013.07.029. Epub 2013 Aug 14. — View Citation

Taylor SF, Liberzon I. Neural correlates of emotion regulation in psychopathology. Trends Cogn Sci. 2007 Oct;11(10):413-8. Review. — View Citation

ter Horst GJ. Estrogen in the limbic system. Vitam Horm. 2010;82:319-38. doi: 10.1016/S0083-6729(10)82017-5. Review. — View Citation

Van Kempen TA, Kahlid S, Gonzalez AD, Spencer-Segal JL, Tsuda MC, Ogawa S, McEwen BS, Waters EM, Milner TA. Sex and estrogen receptor expression influence opioid peptide levels in the mouse hippocampal mossy fiber pathway. Neurosci Lett. 2013 Sep 27;552:66-70. doi: 10.1016/j.neulet.2013.07.048. Epub 2013 Aug 7. — View Citation

Walf AA, Frye CA. ERbeta-selective estrogen receptor modulators produce antianxiety behavior when administered systemically to ovariectomized rats. Neuropsychopharmacology. 2005 Sep;30(9):1598-609. — View Citation

Walf 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. — View Citation

Walf AA, Rhodes ME, Frye CA. Antidepressant effects of ERbeta-selective estrogen receptor modulators in the forced swim test. Pharmacol Biochem Behav. 2004 Jul;78(3):523-9. — View Citation

Yassa MA, Stark SM, Bakker A, Albert MS, Gallagher M, Stark CE. High-resolution structural and functional MRI of hippocampal CA3 and dentate gyrus in patients with amnestic Mild Cognitive Impairment. Neuroimage. 2010 Jul 1;51(3):1242-52. doi: 10.1016/j.neuroimage.2010.03.040. Epub 2010 Mar 23. — View Citation

Yim IS, Glynn LM, Schetter CD, Hobel CJ, Chicz-Demet A, Sandman CA. Prenatal beta-endorphin as an early predictor of postpartum depressive symptoms in euthymic women. J Affect Disord. 2010 Sep;125(1-3):128-33. doi: 10.1016/j.jad.2009.12.009. Epub 2010 Jan 3. — View Citation

Young RC, Biggs JT, Ziegler VE, Meyer DA. A rating scale for mania: reliability, validity and sensitivity. Br J Psychiatry. 1978 Nov;133:429-35. — View Citation

* Note: There are 58 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary 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. At week 33 of pregnancy
Secondary 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. 4 Weeks
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