Biological Triggers of Depression in Pregnancy

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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The Role of Kynurenine Pathway Metabolites in Perinatal Depression and Suicidality

Conditions
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Depression and Suicide, Mood Disorders, Other Perinatal Conditions

Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pre-partum<br>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<br>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. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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). | 

Secondary Outcome Measures

| Outcome Measure | 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 | Analysis of the expression of the inflammatory cytokine IL-6 in placental tissue | At delivery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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depression, mood disorder, post-partum depression, suicidality, post-partum suicidality, perinatal depression, perinatal mood disorder, inflammation, kynurenine pathway, glutamate