A Study of Pregnant and Postpartum Women With and Without Mood Disorders

Major Depressive Disorder Clinical Trial

Official title:

A Prospective Study of Pregnant and Postpartum Women With and Without Mood Disorders

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03615794
• Other study ID #: IRB00027369
• Status: Recruiting
• Start date: October 1, 2017
• Est. completion date: October 2024

Study information

• Verified date: May 2023
• Source: Johns Hopkins University
• Contact: Jennifer Payne, MD
• Phone: 410-502-0050
• Email: jlp4n[@]hscmail.mcc.virginia.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study is looking at genetic, biological, and environmental causes and how all three may work together to cause postpartum mood episodes. Participants will have psychiatric histories taken and will be monitored throughout pregnancy and during the postpartum period for the development of depressive or other mood episodes. Biological measures, including hormone levels, immunological measures, and growth factors will be collected. Environmental factors such as sleep deprivation and stress will also be measured. These factors will be considered in the setting of genetic and epigenetic data with the hope that investigators will ultimately be able to predict the onset of postpartum mood episodes in this vulnerable population.

Description:

Postpartum Depression (PPD) is a serious syndrome which resembles a major depressive episode and occurs in 10-20% of all mothers in the year following delivery. In addition, 20 - 30 % of women with Bipolar Disorder will experience postpartum psychosis (mania) and at least 20 % will experience a postpartum depression with some estimates as high as 65%. The postpartum time therefore represents a natural experiment that, in the setting of prospective monitoring, will allow the measurement of biological, genetic, and environmental factors that may impact the development of mood episodes. Data was previously collected in "A Prospective Study of Postpartum Mood Episodes in Women with Affective disorders." Investigators followed 93 women with a history of a mood disorder (Major Depressive Disorder, Bipolar I, Bipolar II or Bipolar Not Otherwise Specified) through pregnancy and up to three months postpartum. This was a very ill sample and around 75% of the participants met Diagnostic and Statistical Manual (DSM)-IV criteria for a Major Depressive Episode either during pregnancy, postpartum or both. Of those that were well during the 3rd trimester (N=38), 40% became depressed within 4 weeks of delivery, despite the fact that 80% were taking psychiatric medications. Of those that developed Postpartum Depression, 53% had a family history of Postpartum Depression compared to 12% of those that did not develop Postpartum Depression, thus demonstrating a potential genetic basis for Postpartum Depression. Using this sample, investigators were able to identify epigenetic biomarkers that were predictive of Postpartum Depressive episodes. Investigators now seek to replicate and extend investigators' previous findings by identifying and following a second sample of women with mood disorders through pregnancy and into the postpartum time period and, in addition, collect a sample of pregnant women who do not have a history of mood disorder as a control sample. These women will have psychiatric histories taken and will be monitored throughout pregnancy and during the postpartum period for the development of depressive or other mood episodes. In addition to clinical data, biological measures such as hormone levels, immunological measures and growth factors will be taken. Environmental factors such as sleep deprivation and stress will also be measured. These factors will be considered in the setting of genetic and epigenetic data with the hope that investigators will ultimately be able to predict the onset of postpartum mood episodes in this vulnerable population. An understanding of the biological basis of postpartum episodes will ultimately shed light on the vulnerability to Major Depressive Disorder and Bipolar Disorder in general

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 400
• Est. completion date: October 2024
• Est. primary completion date: July 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• Pregnant women with singleton pregnancies
• With or without a history of a mood disorder (MDD, Bipolar I, Bipolar II or Bipolar NOS)

Exclusion Criteria:

• Current active suicidal ideation
• Medical or psychiatric instability
• Active substance abuse or dependence during the last 90 days
• Presence or development of significant pregnancy conditions that may have independent effects on outcomes

Related Conditions & MeSH terms

• Bipolar Disorder
• Depression, Postpartum
• Depressive Disorder
• Depressive Disorder, Major
• Disease
• Major Depressive Disorder
• Mood Disorders
• Postpartum Depression
• Postpartum Psychosis

Locations

Country	Name	City	State
United States	550 North Broadway	Baltimore	Maryland
United States	University of Virginia	Charlottesville	Virginia

Sponsors (2)

Lead Sponsor	Collaborator
Johns Hopkins University	University of Virginia

Country where clinical trial is conducted

United States, 

References & Publications (51)

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

35) O'Hara MW, Varner, MW. (1986). Assessing stressful life events associated with childbearing: The Peripartum Events Scale. J of Repro and Inf Psych 4: 85-98.

Akman I, Kuscu K, Ozdemir N, Yurdakul Z, Solakoglu M, Orhan L, Karabekiroglu A, Ozek E. Mothers' postpartum psychological adjustment and infantile colic. Arch Dis Child. 2006 May;91(5):417-9. doi: 10.1136/adc.2005.083790. Epub 2006 Feb 1. — View Citation

Bernstein, D. and L. Fink, Manual for the childhood trauma questionnaire. The Psychological Corporation, New York, 1998

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. — View Citation

Bratfos O, Haug JO. Puerperal mental disorders in manic-depressive females. Acta Psychiatr Scand. 1966;42(3):285-94. doi: 10.1111/j.1600-0447.1966.tb01933.x. No abstract available. — View Citation

Campbell SB, Cohn JF. Prevalence and correlates of postpartum depression in first-time mothers. J Abnorm Psychol. 1991 Nov;100(4):594-9. doi: 10.1037//0021-843x.100.4.594. — View Citation

Cohen LS, Altshuler LL, Harlow BL, Nonacs R, Newport DJ, Viguera AC, Suri R, Burt VK, Hendrick V, Reminick AM, Loughead A, Vitonis AF, Stowe ZN. Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment. JAMA. 2006 Feb 1;295(5):499-507. doi: 10.1001/jama.295.5.499. Erratum In: JAMA. 2006 Jul 12;296(2):170. — View Citation

Cohen LS, Nonacs RM, Bailey JW, Viguera AC, Reminick AM, Altshuler LL, Stowe ZN, Faraone SV. Relapse of depression during pregnancy following antidepressant discontinuation: a preliminary prospective study. Arch Womens Ment Health. 2004 Oct;7(4):217-21. doi: 10.1007/s00737-004-0059-3. Epub 2004 Aug 30. — View Citation

Cohen S, Kamarck T, Mermelstein R. A global measure of perceived stress. J Health Soc Behav. 1983 Dec;24(4):385-96. No abstract available. — View Citation

Cox JL, Murray D, Chapman G. A controlled study of the onset, duration and prevalence of postnatal depression. Br J Psychiatry. 1993 Jul;163:27-31. doi: 10.1192/bjp.163.1.27. — View Citation

Davidson J, Robertson E. A follow-up study of post partum illness, 1946-1978. Acta Psychiatr Scand. 1985 May;71(5):451-7. doi: 10.1111/j.1600-0447.1985.tb05057.x. — View Citation

Dean C, Williams RJ, Brockington IF. Is puerperal psychosis the same as bipolar manic-depressive disorder? A family study. Psychol Med. 1989 Aug;19(3):637-47. doi: 10.1017/s0033291700024235. — View Citation

Dietz PM, Williams SB, Callaghan WM, Bachman DJ, Whitlock EP, Hornbrook MC. Clinically identified maternal depression before, during, and after pregnancies ending in live births. Am J Psychiatry. 2007 Oct;164(10):1515-20. doi: 10.1176/appi.ajp.2007.06111893. — View Citation

DiPietro JA, Costigan KA, Gurewitsch ED. Fetal response to induced maternal stress. Early Hum Dev. 2003 Nov;74(2):125-38. doi: 10.1016/j.earlhumdev.2003.07.001. — 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. — View Citation

Flynn HA, Davis M, Marcus SM, Cunningham R, Blow FC. Rates of maternal depression in pediatric emergency department and relationship to child service utilization. Gen Hosp Psychiatry. 2004 Jul-Aug;26(4):316-22. doi: 10.1016/j.genhosppsych.2004.03.009. — View Citation

Forty L, Jones L, Macgregor S, Caesar S, Cooper C, Hough A, Dean L, Dave S, Farmer A, McGuffin P, Brewster S, Craddock N, Jones I. Familiality of postpartum depression in unipolar disorder: results of a family study. Am J Psychiatry. 2006 Sep;163(9):1549-53. doi: 10.1176/ajp.2006.163.9.1549. — View Citation

Frank E, Kupfer DJ, Jacob M, Blumenthal SJ, Jarrett DB. Pregnancy-related affective episodes among women with recurrent depression. Am J Psychiatry. 1987 Mar;144(3):288-93. doi: 10.1176/ajp.144.3.288. — View Citation

Grace SL, Evindar A, Stewart DE. The effect of postpartum depression on child cognitive development and behavior: a review and critical analysis of the literature. Arch Womens Ment Health. 2003 Nov;6(4):263-74. doi: 10.1007/s00737-003-0024-6. — 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

Holmes TH, Rahe RH. The Social Readjustment Rating Scale. J Psychosom Res. 1967 Aug;11(2):213-8. doi: 10.1016/0022-3999(67)90010-4. No abstract available. — View Citation

Jones I, Craddock N. Familiality of the puerperal trigger in bipolar disorder: results of a family study. Am J Psychiatry. 2001 Jun;158(6):913-7. doi: 10.1176/appi.ajp.158.6.913. — View Citation

Jones I, Hamshere M, Nangle JM, Bennett P, Green E, Heron J, Segurado R, Lambert D, Holmans P, Corvin A, Owen M, Jones L, Gill M, Craddock N. Bipolar affective puerperal psychosis: genome-wide significant evidence for linkage to chromosome 16. Am J Psychiatry. 2007 Jul;164(7):1099-104. doi: 10.1176/ajp.2007.164.7.1099. — View Citation

Jones I, Middle F, McCandless F, Coyle N, Robertson E, Brockington I, Lendon C, Craddock N. Molecular genetic studies of bipolar disorder and puerperal psychosis at two polymorphisms in the estrogen receptor alpha gene (ESR 1). Am J Med Genet. 2000 Dec 4;96(6):850-3. doi: 10.1002/1096-8628(20001204)96:63.0.co;2-1. — View Citation

Kendell RE, Chalmers JC, Platz C. Epidemiology of puerperal psychoses. Br J Psychiatry. 1987 May;150:662-73. doi: 10.1192/bjp.150.5.662. Erratum In: Br J Psychiatry 1987 Jul;151:135. — View Citation

Kimmel M, Hess E, Roy PS, Palmer JT, Meltzer-Brody S, Meuchel JM, Bost-Baxter E, Payne JL. Family history, not lack of medication use, is associated with the development of postpartum depression in a high-risk sample. Arch Womens Ment Health. 2015 Feb;18(1):113-21. doi: 10.1007/s00737-014-0432-9. Epub 2014 Jul 1. — View Citation

Lee KA. Self-reported sleep disturbances in employed women. Sleep. 1992 Dec;15(6):493-8. doi: 10.1093/sleep/15.6.493. — View Citation

Mahon PB, Payne JL, MacKinnon DF, Mondimore FM, Goes FS, Schweizer B, Jancic D; NIMH Genetics Initiative Bipolar Disorder Consortium; BiGS Consortium; Coryell WH, Holmans PA, Shi J, Knowles JA, Scheftner WA, Weissman MM, Levinson DF, DePaulo JR Jr, Zandi PP, Potash JB. Genome-wide linkage and follow-up association study of postpartum mood symptoms. Am J Psychiatry. 2009 Nov;166(11):1229-37. doi: 10.1176/appi.ajp.2009.09030417. Epub 2009 Sep 15. — 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. — View Citation

Meyer TJ, Miller ML, Metzger RL, Borkovec TD. Development and validation of the Penn State Worry Questionnaire. Behav Res Ther. 1990;28(6):487-95. doi: 10.1016/0005-7967(90)90135-6. — View Citation

Misri S, Eng AB, Abizadeh J, Blackwell E, Spidel A, Oberlander TF. Factors impacting decisions to decline or adhere to antidepressant medication in perinatal women with mood and anxiety disorders. Depress Anxiety. 2013 Nov;30(11):1129-36. doi: 10.1002/da.22137. Epub 2013 Jun 18. — View Citation

Murphy-Eberenz K, Zandi PP, March D, Crowe RR, Scheftner WA, Alexander M, McInnis MG, Coryell W, Adams P, DePaulo JR Jr, Miller EB, Marta DH, Potash JB, Payne J, Levinson DF. Is perinatal depression familial? J Affect Disord. 2006 Jan;90(1):49-55. doi: 10.1016/j.jad.2005.10.006. Epub 2005 Dec 5. — View Citation

O'Donnell KJ, Bugge Jensen A, Freeman L, Khalife N, O'Connor TG, Glover V. Maternal prenatal anxiety and downregulation of placental 11beta-HSD2. Psychoneuroendocrinology. 2012 Jun;37(6):818-26. doi: 10.1016/j.psyneuen.2011.09.014. Epub 2011 Oct 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

Payne JL, MacKinnon DF, Mondimore FM, McInnis MG, Schweizer B, Zamoiski RB, McMahon FJ, Nurnberger JI Jr, Rice JP, Scheftner W, Coryell W, Berrettini WH, Kelsoe JR, Byerley W, Gershon ES, DePaulo JR Jr, Potash JB. Familial aggregation of postpartum mood symptoms in bipolar disorder pedigrees. Bipolar Disord. 2008 Feb;10(1):38-44. doi: 10.1111/j.1399-5618.2008.00455.x. — View Citation

Payne JL, Roy PS, Murphy-Eberenz K, Weismann MM, Swartz KL, McInnis MG, Nwulia E, Mondimore FM, MacKinnon DF, Miller EB, Nurnberger JI, Levinson DF, DePaulo JR Jr, Potash JB. Reproductive cycle-associated mood symptoms in women with major depression and bipolar disorder. J Affect Disord. 2007 Apr;99(1-3):221-9. doi: 10.1016/j.jad.2006.08.013. Epub 2006 Oct 2. — View Citation

Reich T, Winokur G. Postpartum psychoses in patients with manic depressive disease. J Nerv Ment Dis. 1970 Jul;151(1):60-8. doi: 10.1097/00005053-197007000-00008. No abstract available. — View Citation

Shadigian E, Bauer ST. Pregnancy-associated death: a qualitative systematic review of homicide and suicide. Obstet Gynecol Surv. 2005 Mar;60(3):183-90. doi: 10.1097/01.ogx.0000155967.72418.6b. — View Citation

Shivakumar G, Johnson NL, McIntire DD, Leveno K. Progression of major depression during pregnancy and postpartum: a preliminary study. J Matern Fetal Neonatal Med. 2014 Apr;27(6):571-6. doi: 10.3109/14767058.2013.825599. Epub 2013 Aug 19. — View Citation

Sichel DA, Cohen LS, Robertson LM, Ruttenberg A, Rosenbaum JF. Prophylactic estrogen in recurrent postpartum affective disorder. Biol Psychiatry. 1995 Dec 15;38(12):814-8. doi: 10.1016/0006-3223(95)00063-1. — View Citation

Sit DK, Perel JM, Helsel JC, Wisner KL. Changes in antidepressant metabolism and dosing across pregnancy and early postpartum. J Clin Psychiatry. 2008 Apr;69(4):652-8. doi: 10.4088/jcp.v69n0419. — View Citation

Somerville S, Dedman K, Hagan R, Oxnam E, Wettinger M, Byrne S, Coo S, Doherty D, Page AC. The Perinatal Anxiety Screening Scale: development and preliminary validation. Arch Womens Ment Health. 2014 Oct;17(5):443-54. doi: 10.1007/s00737-014-0425-8. Epub 2014 Apr 4. — View Citation

Spinelli MG. Maternal infanticide associated with mental illness: prevention and the promise of saved lives. Am J Psychiatry. 2004 Sep;161(9):1548-57. doi: 10.1176/appi.ajp.161.9.1548. — View Citation

Viguera AC, Tondo L, Koukopoulos AE, Reginaldi D, Lepri B, Baldessarini RJ. Episodes of mood disorders in 2,252 pregnancies and postpartum periods. Am J Psychiatry. 2011 Nov;168(11):1179-85. doi: 10.1176/appi.ajp.2011.11010148. Epub 2011 Jul 28. — View Citation

Wisner KL, Perel JM, Peindl KS, Hanusa BH, Findling RL, Rapport D. Prevention of recurrent postpartum depression: a randomized clinical trial. J Clin Psychiatry. 2001 Feb;62(2):82-6. doi: 10.4088/jcp.v62n0202. — View Citation

Wisner KL, Perel JM, Peindl KS, Hanusa BH, Piontek CM, Findling RL. Prevention of postpartum depression: a pilot randomized clinical trial. Am J Psychiatry. 2004 Jul;161(7):1290-2. doi: 10.1176/appi.ajp.161.7.1290. — View Citation

Wisner KL, Wheeler SB. Prevention of recurrent postpartum major depression. Hosp Community Psychiatry. 1994 Dec;45(12):1191-6. doi: 10.1176/ps.45.12.1191. — View Citation

Yonkers KA, Gotman N, Smith MV, Forray A, Belanger K, Brunetto WL, Lin H, Burkman RT, Zelop CM, Lockwood CJ. Does antidepressant use attenuate the risk of a major depressive episode in pregnancy? Epidemiology. 2011 Nov;22(6):848-54. doi: 10.1097/EDE.0b013e3182306847. — View Citation

Yonkers KA, Ramin SM, Rush AJ, Navarrete CA, Carmody T, March D, Heartwell SF, Leveno KJ. Onset and persistence of postpartum depression in an inner-city maternal health clinic system. Am J Psychiatry. 2001 Nov;158(11):1856-63. doi: 10.1176/appi.ajp.158.11.1856. — 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. doi: 10.1192/bjp.133.5.429. — View Citation

* Note: There are 51 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Major depressive episode	Development of a major depressive episode within the first 4 weeks postpartum	4 weeks postpartum
Secondary	Postpartum depression as assessed by Whole blood analysis	Analyze whole blood to identify genetic and epigenetic risk factors for postpartum depression.	Pregnancy and up to 6 months postpartum
Secondary	Postpartum depression risk as assessed by serum analysis	Analyze serum samples to identify hormonal and immunological risk factors for postpartum depression.	Pregnancy and up to 6 months postpartum