# Understanding the Relationship Between Environmental Endocrine Disrupting Chemicals, Neuropsychiatric Outcomes, and Related Biological Processes in Depression

> **NIH NIH K23** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $246,770

## Abstract

Environmental endocrine disrupting chemicals (EDCs) are associated with multiple adverse health effects. Early-
life exposures alter neurobehavioral trajectories, with increased risk for depression and poorer cognitive
functioning in childhood. However, very few studies have evaluated the effects of EDC exposure in later life
despite ongoing exposure. Patients with a history of major depression (MDD) are at increased risk for
neuropsychiatric symptoms such as low mood and cognitive dysfunction and this risk is further elevated in
women during the menopausal and post-menopausal period. Preclinical and clinical evidence suggests that
EDCs affect a number of biological variables implicated in mood and cognitive disorders, including inflammatory
biomarkers, brain-derived neurotrophic factor (BDNF), and sex hormones. The proposed study seeks to better
understand how EDCs affect mood and cognition in postmenopausal women with and without depression. We
propose to evaluate 1) the association between EDCs and neuropsychiatric symptoms (mood and cognition) in
postmenopausal women with MDD and without mood disorders (healthy controls; HC), 2) the relationship
between EDCs and biological variables including inflammatory cytokines like C-reactive protein, interleukin-6,
and tumor necrosis factor-α, BDNF, and sex hormones including estradiol and testosterone, and 3) whether the
biological variables of interest mediate any potential association of EDCs with neuropsychiatric outcomes. We
will leverage ongoing data collection of an existing study of postmenopausal women including depression rating
scale scores and detailed cognitive assessment data, as well as serum cytokine, BDNF, and sex hormone levels.
Urinary bisphenols and a suite of 16 phthalate metabolites will be measured in 75 MDD and 75 HC subjects.
Urine will be collected at 2 timepoints (at recruitment and 1 month later), then pooled for EDC assessment.
Regression and statistical methods for mixtures will be used to assess relationships between individual EDCs
and their mixtures with neuropsychiatric outcomes and biomarkers. Mediation analysis will explore the direct and
indirect effect of EDCs on outcome measures via the biological variables. Career development plan goals include
gaining competency in the interpretation of environmental exposures and inflammatory data and in biostatistics,
especially mixture methods of analysis. Training goals will be met by coursework, workshops/seminars,
conferences, lab experience, readings, and mentorship. Training experiences will mostly take place at Harvard-
affiliated BWH and HSPH. This project will identify emotional and cognitive effects and relevant biological effects
of EDCs in a population vulnerable to neuropsychiatric symptoms. Enhanced mechanistic understanding will
allow novel interventions targeting contributory biological variables, such as lifestyle changes or medications that
reduce inflammation, increase BDNF, and regulate sex hormones to mitig...

## Key facts

- **NIH application ID:** 10913574
- **Project number:** 5K23ES034472-02
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Jessica Ann Harder
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $246,770
- **Award type:** 5
- **Project period:** 2023-09-01 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10913574

## Citation

> US National Institutes of Health, RePORTER application 10913574, Understanding the Relationship Between Environmental Endocrine Disrupting Chemicals, Neuropsychiatric Outcomes, and Related Biological Processes in Depression (5K23ES034472-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10913574. Licensed CC0.

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