Biological Triggers of Depression in Pregnancy

NCT02566980 | Completed DMC

• 2 other identifiers: 14-458M1R01MH104622-01
• Study Type: observational
• Target: 209
• Locations: 1 country
• Sites: 3

Brief Summary

The goal of the study is to define and measure biological processes that contribute to the underlying pathophysiologic process of peri-partum depression to be used for identifying those at risk for developing it. This knowledge may also generate novel drug targets for peripartum depression that may be applicable to other types of depression.

Conditions

Depression and Suicide; Mood Disorders; Other Perinatal Conditions

Keywords

depression; mood disorder; post-partum depression; suicidality; post-partum suicidality; perinatal depression; perinatal mood disorder; inflammation; kynurenine pathway; glutamate

Outcome Measures

Primary Outcomes (4)

• Change in activity of the enzyme aminocarboxymuconate semialdehyde decarboxylase ACMSD in blood during pregnancy

  Blood levels of quinolinic acid and picolinic acid (product of ACMSD) at three timepoints during pregnancy and one time-point after pregnancy

  Up to pregnancy week 13 (1st sample), up to week 25 (second sample) and up to delivery (3rd sample) and post-partum (4th sample, within 6 months after delivery)

• Activity of the enzyme aminocarboxymuconate semialdehyde decarboxylase ACMSD in placenta

  Placenta levels of quinolinic acid and picolinic acid

  At delivery

• Increase in depressive symptoms

  Assessment of depressive symptoms by means of the Edinburgh Postnatal Depression Scale

  Up to pregnancy week 13 (1st assessment), up to week 25 (second assessment) and up to delivery (3rd assessment) and post-partum (4th assessment, within 6 months after delivery)

• Suicidal symptoms

  Assessment of suicidal symptoms by means of the Columbia Suicide Severity Rating Scale

  Post-partum (within 6 months after delivery).

Secondary Outcomes (2)

• Change in blood inflammation

  Up to pregnancy week 13 (1st sample), up to week 25 (second sample) and up to delivery (3rd sample) and post-partum (4th sample, within 6 months after delivery)

• Placenta inflammation

  At delivery

Study Arms (2)

Pre-partum

130 pregnant women will be enrolled in first trimester. Healthy women or those with any degree of depressive symptoms are eligible. Blood samples and psychiatric assessments will take place once every trimester and once in the post-partum. At delivery placenta will be collected. Enrollment takes place at Spectrum Health Ob/gyn out-patient clinics in Grand Rapids, Michigan.

Post-partum

50-100 women experiencing perinatal depression with and without suicidality will be enrolled from a partial hospitalization program, the Mother and Baby unit as well as outpatient clinics at Pine Rest Christian Mental Health Services, Grand Rapids, Michigan.

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Pregnant females age 18 and older, psychiatrically healthy or depressed; post-partum females experiencing perinatal depression with and without suicide ideation.

You may qualify if:

• Pre-partum cohort:
• All races and national origins of pregnant females.
• Age 18 and older.
• English speaking.
• Able to give informed consent.
• Able to comply with study procedures.

You may not qualify if:

• Pre-partum cohort:
• Non-pregnant females
• Patients with psychotic symptoms and/or severe cognitive impairment that interfere with their ability to give informed consent or to complete study assessments.
• Patients that cannot read and write in English as research measures used have only been validated in English speaking populations.
• Patients that have blood-borne chronic infections including hepatitis B, C, or HIV as established at routine pregnancy blood screens; they will be excluded as the laboratory facilities do not approve processing of their tissue for safety reasons.
• Patients who have any schizophrenia spectrum disorder or bipolar disorder type 1 (based on self report and SCID interview); these patients will be excluded as the neurobiology of these disorders are different from peripartum depression.
• Patients who report ongoing substance abuse or dependence (in the past 3 months).
• Post-partum cohort:
• All races and national origins of females who delivered a child vaginally or by caesarian section up to 6 months prior to enrollment.
• Age 18 and older.
• Edinburgh Perinatal Depression Rating Scale score of 10 and above and/or endorsed suicide ideation on the CSSRS.
• Depressive symptoms which began or worsened (if already present) during pregnancy or up to 4 weeks post-partum.
• Able to give informed consent.
• Able to comply with and complete study procedures.
• English speaking.

Sponsors & Collaborators

• Michigan State University: lead
• Pine Rest Christian Mental Health Services: collaborator
• Van Andel Research Institute: collaborator
• Corewell Health West: collaborator
• National Institute of Mental Health (NIMH): collaborator

Study Sites (3)

Spectrum Health System

Grand Rapids, Michigan, 49503, United States

Location

Van Andel Research Institute

Grand Rapids, Michigan, 49503, United States

Location

Pine Rest Christian Mental Health Services

Grand Rapids, Michigan, 49548, United States

Location

Related Publications (23)

• National Institute of Mental Health (NIMH), Statistics Use of Mental Health Services and Treatment among Adults. Availabe on-line at http://www.nimh.nih.gov/statistics/3USE_MT_ADULT.shtml.

  BACKGROUND

• World Health Organization (WHO). What Is Depression. Available on-line at http://www.who.int/mental_health/management/depression/definition/en/

  BACKGROUND

• First MB, Spitzer RL, Gibbon M, Williams JBW. Structured Clinical Interview for DSM-IV Axis I Disorders - Patient Edition (SCID-I/P, Version 2.0), Biometrics Research Department, New York State Psychiatric Institute, 1995.

  BACKGROUND

• Centers for Disease Control and Prevention (CDC). Prevalence of self-reported postpartum depressive symptoms--17 states, 2004-2005. MMWR Morb Mortal Wkly Rep. 2008 Apr 11;57(14):361-6.

  PMID: 18401329 BACKGROUND

• 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.

  PMID: 17898342 BACKGROUND

• Marcus SM, Heringhausen JE. Depression in childbearing women: when depression complicates pregnancy. Prim Care. 2009 Mar;36(1):151-65, ix. doi: 10.1016/j.pop.2008.10.011.

  PMID: 19231607 BACKGROUND

• Meltzer-Brody S, Boschloo L, Jones I, Sullivan PF, Penninx BW. The EPDS-Lifetime: assessment of lifetime prevalence and risk factors for perinatal depression in a large cohort of depressed women. Arch Womens Ment Health. 2013 Dec;16(6):465-73. doi: 10.1007/s00737-013-0372-9. Epub 2013 Aug 1.

  PMID: 23904137 BACKGROUND

• Mian AI. Depression in pregnancy and the postpartum period: balancing adverse effects of untreated illness with treatment risks. J Psychiatr Pract. 2005 Nov;11(6):389-96. doi: 10.1097/00131746-200511000-00005.

  PMID: 16304507 BACKGROUND

• Davalos DB, Yadon CA, Tregellas HC. Untreated prenatal maternal depression and the potential risks to offspring: a review. Arch Womens Ment Health. 2012 Feb;15(1):1-14. doi: 10.1007/s00737-011-0251-1. Epub 2012 Jan 4.

  PMID: 22215285 BACKGROUND

• Anderson G, Maes M. Postpartum depression: psychoneuroimmunological underpinnings and treatment. Neuropsychiatr Dis Treat. 2013;9:277-87. doi: 10.2147/NDT.S25320. Epub 2013 Feb 21.

  PMID: 23459664 BACKGROUND

• Groer MW, Morgan K. Immune, health and endocrine characteristics of depressed postpartum mothers. Psychoneuroendocrinology. 2007 Feb;32(2):133-9. doi: 10.1016/j.psyneuen.2006.11.007. Epub 2007 Jan 3.

  PMID: 17207585 BACKGROUND

• Jolley SN, Elmore S, Barnard KE, Carr DB. Dysregulation of the hypothalamic-pituitary-adrenal axis in postpartum depression. Biol Res Nurs. 2007 Jan;8(3):210-22. doi: 10.1177/1099800406294598.

  PMID: 17172320 BACKGROUND

• Koleva H, Stuart S, O'Hara MW, Bowman-Reif J. Risk factors for depressive symptoms during pregnancy. Arch Womens Ment Health. 2011 Apr;14(2):99-105. doi: 10.1007/s00737-010-0184-0. Epub 2010 Sep 25.

  PMID: 20872153 BACKGROUND

• Meltzer-Brody S. Mental illness is prevalent among U.K. women in the perinatal period and is associated with socioeconomic deprivation. Evid Based Ment Health. 2013 May;16(2):57. doi: 10.1136/eb-2013-101226. Epub 2013 Mar 16. No abstract available.

  PMID: 23503977 BACKGROUND

• Arck PC, Hecher K. Fetomaternal immune cross-talk and its consequences for maternal and offspring's health. Nat Med. 2013 May;19(5):548-56. doi: 10.1038/nm.3160. Epub 2013 May 7.

  PMID: 23652115 BACKGROUND

• Rowe JH, Ertelt JM, Xin L, Way SS. Regulatory T cells and the immune pathogenesis of prenatal infection. Reproduction. 2013 Oct 21;146(6):R191-203. doi: 10.1530/REP-13-0262. Print 2013 Dec.

  PMID: 23929902 BACKGROUND

• Honig A, Rieger L, Kapp M, Sutterlin M, Dietl J, Kammerer U. Indoleamine 2,3-dioxygenase (IDO) expression in invasive extravillous trophoblast supports role of the enzyme for materno-fetal tolerance. J Reprod Immunol. 2004 Apr;61(2):79-86. doi: 10.1016/j.jri.2003.11.002.

  PMID: 15063631 BACKGROUND

• Zhu BT. Development of selective immune tolerance towards the allogeneic fetus during pregnancy: Role of tryptophan catabolites (Review). Int J Mol Med. 2010 Jun;25(6):831-5. doi: 10.3892/ijmm_00000411.

  PMID: 20428785 BACKGROUND

• Manuelpillai U, Ligam P, Smythe G, Wallace EM, Hirst J, Walker DW. Identification of kynurenine pathway enzyme mRNAs and metabolites in human placenta: up-regulation by inflammatory stimuli and with clinical infection. Am J Obstet Gynecol. 2005 Jan;192(1):280-8. doi: 10.1016/j.ajog.2004.06.090.

  PMID: 15672037 BACKGROUND

• Lindqvist D, Janelidze S, Hagell P, Erhardt S, Samuelsson M, Minthon L, Hansson O, Bjorkqvist M, Traskman-Bendz L, Brundin L. Interleukin-6 is elevated in the cerebrospinal fluid of suicide attempters and related to symptom severity. Biol Psychiatry. 2009 Aug 1;66(3):287-92. doi: 10.1016/j.biopsych.2009.01.030. Epub 2009 Mar 6.

  PMID: 19268915 BACKGROUND

• Janelidze S, Mattei D, Westrin A, Traskman-Bendz L, Brundin L. Cytokine levels in the blood may distinguish suicide attempters from depressed patients. Brain Behav Immun. 2011 Feb;25(2):335-9. doi: 10.1016/j.bbi.2010.10.010. Epub 2010 Oct 15.

  PMID: 20951793 BACKGROUND

• Erhardt S, Lim CK, Linderholm KR, Janelidze S, Lindqvist D, Samuelsson M, Lundberg K, Postolache TT, Traskman-Bendz L, Guillemin GJ, Brundin L. Connecting inflammation with glutamate agonism in suicidality. Neuropsychopharmacology. 2013 Apr;38(5):743-52. doi: 10.1038/npp.2012.248. Epub 2012 Dec 3.

  PMID: 23299933 BACKGROUND

• Sha Q, Madaj Z, Keaton S, Escobar Galvis ML, Smart L, Krzyzanowski S, Fazleabas AT, Leach R, Postolache TT, Achtyes ED, Brundin L. Cytokines and tryptophan metabolites can predict depressive symptoms in pregnancy. Transl Psychiatry. 2022 Jan 26;12(1):35. doi: 10.1038/s41398-022-01801-8.

  PMID: 35078975 DERIVED

Related Links

• Van Andel Institutes
• Pine Rest Christian Mental Health Services

Biospecimen

Retention: SAMPLES WITH DNA

Adult Blood Cord Blood Placenta

MeSH Terms

Conditions

Depression; Suicide; Mood Disorders; Depression, Postpartum; Suicidal Ideation; Inflammation

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Self-Injurious Behavior; Mental Disorders; Puerperal Disorders; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Depressive Disorder; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Lena Brundin, MD, PhD

  Michigan State University, Van Andel Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Division of Psychiatry and Behavioral Medicine

Study Record Dates

• First Submitted: September 25, 2015
• First Posted: October 2, 2015
• Study Start: October 23, 2014
• Primary Completion: February 28, 2017
• Study Completion: February 28, 2017
• Last Updated: June 28, 2018

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)