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| ID | Type | Description | Link |
|---|---|---|---|
| 1R01MH104622-01 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Pine Rest Christian Mental Health Services | OTHER |
| Van Andel Research Institute | OTHER |
| Corewell Health West | OTHER |
| National Institute of Mental Health (NIMH) |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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). |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Placenta inflammation |
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Inclusion Criteria
Pre-partum cohort:
Exclusion Criteria
Pre-partum cohort:
Inclusion criteria
Post-partum cohort:
Exclusion criteria
Post-partum cohort:
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Pregnant females age 18 and older, psychiatrically healthy or depressed; post-partum females experiencing perinatal depression with and without suicide ideation.
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| Name | Affiliation | Role |
|---|---|---|
| Lena Brundin, MD, PhD | Michigan State University, Van Andel Research Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Spectrum Health System | Grand Rapids | Michigan | 49503 | United States | ||
| Van Andel Research Institute |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| Background | 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. | ||
| 18401329 | 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. |
| Label | URL |
|---|---|
| Van Andel Institutes | View source |
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| ID | Term |
|---|---|
| D003863 | Depression |
| D013405 | Suicide |
| D019964 | Mood Disorders |
| D019052 | Depression, Postpartum |
| D059020 | Suicidal Ideation |
| D007249 | Inflammation |
| ID | Term |
|---|---|
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
| D016728 | Self-Injurious Behavior |
| D001523 | Mental Disorders |
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| NIH |
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Adult Blood Cord Blood Placenta
Analysis of the expression of the inflammatory cytokine IL-6 in placental tissue |
| At delivery |
| Grand Rapids |
| Michigan |
| 49503 |
| United States |
| Pine Rest Christian Mental Health Services | Grand Rapids | Michigan | 49548 | United States |
| 17898342 | 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. |
| 19231607 | 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. |
| 23904137 | 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. |
| 16304507 | 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. |
| 22215285 | 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. |
| 23459664 | 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. |
| 17207585 | 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. |
| 17172320 | 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. |
| 20872153 | 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. |
| 23503977 | 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. |
| 23652115 | 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. |
| 23929902 | 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. |
| 15063631 | 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. |
| 20428785 | 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. |
| 15672037 | 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. |
| 19268915 | 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. |
| 20951793 | 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. |
| 23299933 | 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. |
| 35078975 | Derived | 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. |
| Pine Rest Christian Mental Health Services | View source |
| D011644 |
| Puerperal Disorders |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D003866 | Depressive Disorder |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |