PBDE Exposure, Thyroid Disruption, and Antenatal Depression in African American Women Restricted; Files Only
Mutic, Abby (Spring 2019)
Published
Abstract
Background: Polybrominated diphenyl ethers (PBDEs) are environmental chemicals once used to prevent or reduce flammability. Phased out of production nearly 10 years ago, PBDEs remain ubiquitous in the environment. These persistent endocrine disrupting chemicals have potential to disrupt normal neuroendocrine pathways such as thyroid hormone synthesis resulting in depression. Pregnant African American (AA) women living in urban areas may be at higher risk of depression due to high PBDE exposure. This study examined complex interactions between PBDE serum concentrations, tyrosine metabolites within thyroid hormone synthesis, and the risk of antenatal depression in pregnant AA women.
Methods: Nested in a larger study, data was collected from 193 pregnant AA women between 8-14 weeks gestation. Serum PBDEs were determined by GC/MS. Levels of tyrosine-associated metabolites in plasma were determined using apLCMS and xMSanalyzer to improve high-resolution LC/MS. Socio-demographic variables were collected. The Edinburgh Depression Scale (EDS) was used to identify depressive symptoms experienced in the last seven days with a score ≥10 indicating high risk. A weighted quantile sum (WQS) index was constructed for PBDE mixture effect. Linear and logistic regression models investigated associations with PBDE concentrations, WQS, and depression. Seven metabolites within the tyrosine pathway were considered as potential mediators between PBDEs and depression symptoms.
Results: 52 women (26.9%) were at a high risk of depression. BDE-47 was positively associated with depressive symptoms with a 4.52 increased risk of depression (CI 1.50, 13.60) and 1.58 for BDE-99 (CI 1.08, 2.29) for each unit increase in PBDE congener. The WQS index was also positively associated with a higher risk of depression (OR=2.93; CI 1.18, 7.82). Tyrosine metabolite suspects did not mediate the effect of PBDEs on depression scores.
Conclusion: BDE-47 and -99 exposures were associated with an increased risk of depression and Tyrosine metabolites were identified possibly indicating thyroid disruption. However, the metabolites did not mediate the PBDE-depression relationship. Interventions should focus on PBDE exposure mitigation to reduce the risk of depression on vulnerable pregnant women.
Table of Contents
Introduction
Statement of the problem………………………………………………………………………………1
Background…………………………………………………………………………………………………2
Environmental health disparities…………………………………………………………2
Vulnerability of pregnant women…………………………………………………………2
PBDEs as persistent organic pollutants………………………………………………..3
PBDE metabolic pathways and health effects………………………………………..4
Specific Aims………………………..……………………………………………………….6
Conceptual model…………………………………………………………………………………………7
Introduction to manuscripts………………………………………………………………………….7
Relevance to Nursing and Public Health…………………………………………………8
Summary…………………………………………………………………………………………………….9
Manuscript 1: Thyroid Hormone Disruption as a Mediator Between PBDEs and Perinatal Depression
Abstract……………………………………………………………………………………………………..10
Introduction………………………………………………………………………………………………..11
Routes of PBDE exposure…………………………………………………………………………….13
Variability of PBDE exposure within populations…………………………………………..14
PBDEs as endocrine disrupting chemicals……………………………………………………..17
Thyroid function during development…………………………………………………………..18
Thyroid hormone changes during pregnancy…………………………………………………19
Human studies linking PBDE exposure to thyroid disruption…………………………20
Thyroid dysfunction and perinatal depression…………………….25
PBDE-associated depression………………………………………………………………………..31
Conclusion…………………………………………………………………………………………………33
Manuscript 2: Polybrominated diphenyl ether serum concentrations and depressive symptomatology in pregnant African American women
Abstract…………………………………………………………………………………………………….35
Background………………………………………………………………………………………………..37
Methods……………………………………………………………………………………………………40 Measures…………………………………………………………………………………………………..40
Covariates and Confounders………………………………………………………………43
Statistical Analysis……………………………………………………………………………43
Results………………………………………………………………………………………………………44
Discussion…………………………………………………………………………………………………49
Limitations………………………………………………………………………………………52
Conclusion………………………………………………………………………………………53
Manuscript 3: Using tyrosine metabolomics to describe the relationship between serum polybrominated diphenyl ether and depression
Abstract…………………………………………………………………………………………………….56
Background……………………………………………………………………………………………….58
Methods…………………………………………………………………………………………60
Measures…………………………………………………………………………………………60
Statistical Analysis……………………………………………………………………………62
Results………………………………………………………………………………………………………64
Discussion…………………………………………………………………………………………………70
Conclusion…………………………………………………………………………………………………71
Dissertation Conclusion………………………………………………………………………………….73
Manuscript review
“Thyroid hormone disruption as a mediator between polybrominated diphenyl ether and antenatal depression”………………………………………….74
“Polybrominated diphenyl ether serum concentrations and depressive symptomatology in pregnant African American women”………….………..75
“Using tyrosine metabolomics to describe the relationship between serum polybrominated diphenyl ether and depression”……………………….………..76
Strengths and limitations……………………………………………………………………………77
Challenges encountered during study…………………………………………………………..78
Implications for clinical practice………………………………………………………………….79
Recommendations for policy……………………………………………………………………….80
Recommendations for future research………………………………………………………….80
Summary…………………………………………………………………………………………………..81
References……………………………………………………………………………………………………..…83
List of Tables
Table 1. Evidence Table linking PBDE Exposure and Thyroid Dysfunction………………..21
Table 2. Evidence Table linking Thyroid Dysfunction and Perinatal Depression…………27
Table 3. Evidence Table linking PBDEs and Depression…………………………………………..33
Table 4: Demographic characteristics of AA cohort 2014-2015 associated with high depressive symptoms using an EDS cutoff ≥10………………………………………………………..45
Table 5: Health-related characteristics of AA cohort 2014-2015 associated with high depressive symptoms using an EDS cutoff of ≥10……………………………………………………46
Table 6: Wet weight PBDE congeners present in the study population compared to 2013-2014 NHANES data reported in pg/mL serum (N=193)…………………………………..46
Table 7: PBDE concentrations (pg/mL) in serum and risk of antenatal depression among African American cohort at 8-14 weeks gestation (N=193)…………………………….47
Table 8: Multiple logistic regressions of high antenatal depressive symptoms among African American women using an EDS cutoff ≥10……………………………………………….…48
Table 9: Associations between Weighted Quantile Sum Regression Index and high antenatal depression symptoms using an EDS cutoff ≥10 in the study population………49
Table 10: Demographic characteristics of AA cohort 2014-2015 associated with high depressive symptoms (N=193)…………………………………………………………..………………….66
Table 11: Tyrosine-specific metabolic pathways identified by high-resolution metabolomics methods among AA pregnant women (N=193)…………………………………..67
Table 12: Simple linear regression between PBDE exposures and identified tyrosine-specific metabolites (N=193)…………………………………………………………………………………67
Table 13: Results of mediation model of PBDE 47 exposure on tyrosine metabolites and EDS scores (N=193)……………………………………………………………………………………………..68
Supplemental Table 1: Level of detection for Each PBDE Congener…………………………..54
Supplemental Table 2: Comparison of high depressive symptoms using an EDS cutoff ≥10 at 8-14 weeks and 24-30 weeks gestation (N=193)…………………………………………….55
Supplemental Table 3: Causal mediation effects of PBDE exposure on depressive symptoms……………………………………………………………………………………………………………69
List of Figures
Figure 1. Conceptual model depicting two mechanisms between PBDE exposure and depression……………………………………………………………………………………………………………..7
Figure 2. Chemical Structures of BDE -47 and Thyroxine (T4)…………………………………..18
Figure 3: Comparison of Edinburgh Depression Scale Cut Points using PBDE 47……….42
Figure 4: Relationship between PBDE47 and Depressive Symptoms…………………………47
Figure 5. Tyrosine-specific metabolite identification using high-resolution metabolomics and suspect screen analysis (N=193)………………………………………………………………………62
Supplemental Figure 1. Comparison of EDS scores between 8-14 weeks and 24-30 weeks gestation……………………………………………………………………………………………………………..54
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