Biological Triggers of Depression in Pregnancy

Mood Disorders Clinical Trial

Official title:

The Role of Kynurenine Pathway Metabolites in Perinatal Depression and Suicidality

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02566980
• Other study ID #: 14-458M
• Secondary ID: 1R01MH104622-01
• Status: Completed
• Start date: October 23, 2014
• Est. completion date: February 28, 2017

Study information

• Verified date: June 2018
• Source: Michigan State University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Description:

This study analyses the role of inflammation and metabolites of inflammation in perinatal depression. Psychiatric assessments of depression and suicidality will be compared to blood levels of two metabolites of inflammation, quinolinic acid (QUIN) and picolinic acid (PIC), that might regulate nerve cell communication. The levels of these metabolites are regulated by kynurenine pathway enzymes.

Psychiatric symptoms, inflammatory cytokines and levels of the metabolites will be measured throughout pregnancy. Additionally, the investigators are gathering placentas at delivery and determining the degree of inflammation in the tissue in the investigators' laboratory. Inflammatory biomarkers, antibody titers, and key kynurenine pathway enzymes and metabolites from pre- and post partum women, placenta, and cord blood will be measured.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 209
• Est. completion date: February 28, 2017
• Est. primary completion date: February 28, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

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.

Exclusion Criteria

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).

Inclusion criteria

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.

Exclusion criteria

Post-partum cohort:

• Patients with psychotic symptoms and/or severe cognitive impairment that interfere with their ability to give informed consent or to complete study assessments.

• Patients who 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 their routine pregnancy blood screens.

• Patients who have any schizophrenia spectrum disorder or bipolar type 1 (based on the self report and SCID interview).

• Patients who report ongoing substance abuse or dependence (past 3 months).

Related Conditions & MeSH terms

• Depression
• Depression and Suicide
• Depressive Disorder
• Mood Disorders
• Other Perinatal Conditions
• Suicide

Locations

Country	Name	City	State
United States	Pine Rest Christian Mental Health Services	Grand Rapids	Michigan
United States	Spectrum Health System	Grand Rapids	Michigan
United States	Van Andel Research Institute	Grand Rapids	Michigan

Sponsors (5)

Lead Sponsor	Collaborator
Michigan State University	National Institute of Mental Health (NIMH), Pine Rest Christian Mental Health Services, Spectrum Health Hospitals, Van Andel Research Institute

Country where clinical trial is conducted

United States, 

References & Publications (22)

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. Review. — 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. — View Citation

Erhardt S, Lim CK, Linderholm KR, Janelidze S, Lindqvist D, Samuelsson M, Lundberg K, Postolache TT, Träskman-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. — View Citation

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.

Groer MW, Morgan K. Immune, health and endocrine characteristics of depressed postpartum mothers. Psychoneuroendocrinology. 2007 Feb;32(2):133-9. Epub 2007 Jan 3. — View Citation

Hönig A, Rieger L, Kapp M, Sütterlin M, Dietl J, Kämmerer 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. — View Citation

Janelidze S, Mattei D, Westrin Å, Träskman-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. — View Citation

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. — View Citation

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. — View Citation

Lindqvist D, Janelidze S, Hagell P, Erhardt S, Samuelsson M, Minthon L, Hansson O, Björkqvist M, Träskman-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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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.

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. Review. — View Citation

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

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. Review. — View Citation

* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	Activity of the enzyme aminocarboxymuconate semialdehyde decarboxylase ACMSD in placenta	Placenta levels of quinolinic acid and picolinic acid	At delivery
Primary	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)
Primary	Suicidal symptoms	Assessment of suicidal symptoms by means of the Columbia Suicide Severity Rating Scale	Post-partum (within 6 months after delivery).
Secondary	Change in blood inflammation	Analysis of the inflammatory cytokine IL-6 in blood	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)
Secondary	Placenta inflammation	Analysis of the expression of the inflammatory cytokine IL-6 in placental tissue	At delivery

External Links

•   Pine Rest Christian Mental Health Services
•   Spectrum Health
•   Van Andel Institutes