# Brain and Behavioral Indicators of Risk for Parkinsonism among Adolescents with Early Pesticide Exposure

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $612,890

## Abstract

Multiple studies have demonstrated an association between organophosphate (OP) insecticide exposure and
Parkinson's Disease (PD) in adults, but virtually no studies have explored signs of the pathogenic process that
begins long before the appearance of motor symptoms. There is a clear need for prospective studies, including
biomarkers of exposure and brain-based measures, to substantiate a cause-effect relationship and the
development of parkinsonism over time. We have access to a well-characterized community sample—an
urban minority birth cohort that has been followed for 18 years, with a prenatal blood biomarker of exposure to
a common OP pesticide, chlorpyrifos (CPF), and regular assessments of neurodevelopment, including
multimodal brain scans at 12-14 and 18 years. In this cohort, we have shown that prenatal CPF exposure is
associated with motor delay at 2-3 years, and persistent brain, behavioral and subtle motor effects through 11-
12 years of age. We now have a unique opportunity to study the emergence of pre-clinical/non-motor
indicators of PD risk at 18-20 years of age in this cohort. We propose to test the novel hypothesis that prenatal
CPF exposure has long-term motor consequences, including neurological signs and brain-based biomarkers of
PD risk that are measureable early in the pathogenic process, prior to the identification of clinically confirmed
symptoms or diagnosis. We aim to: (1) conduct a single wave of neurological and brain imaging assessment
(using known indicators of PD risk in adult populations) in a subset of the cohort (n=200) at 18-20 years of age.
We hypothesize that those with higher prenatal CPF levels as compared to those with lower levels will show
significantly more signs of early PD risk, as indicated by (a) higher prevalence of pre-clinical extrapyramidal
motor dysfunction (dystonia, bradykinesia, arm tremor); (b) higher prevalence of non-motor symptoms (REM
sleep behavior disorder, autonomic dysfunction, olfactory deficits); and (c) increased prodromal motor markers
(gait variability, inconsistent walking pattern, arm swing asymmetry and lower axial rotation smoothness); (2)
conduct structural MRI for neuromelanin to identify substantia nigra involvement (a biomarker of PD) in these
same subjects. We hypothesize that those with higher prenatal CPF levels as compared to those with lower
levels will show significantly greater substantia nigra involvement marked by a greater decrease in
neuromelanin content; (3) employ an innovative statistical procedure using a vast number of functional and
structural brain characteristics, based on multi-modal imaging data previously collected at 12-14 and 18 years,
to determine whether an exposure-related pattern of neural deficits across modalities (a potential biomarker for
PD) can be detected in our young cohort. We hypothesize that subjects with higher prenatal CPF levels as
compared to those with lower levels will show a distinctive pattern of brain anomalies across mod...

## Key facts

- **NIH application ID:** 9844064
- **Project number:** 5R01ES030039-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** F. DuBois Bowman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $612,890
- **Award type:** 5
- **Project period:** 2019-01-15 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9844064

## Citation

> US National Institutes of Health, RePORTER application 9844064, Brain and Behavioral Indicators of Risk for Parkinsonism among Adolescents with Early Pesticide Exposure (5R01ES030039-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9844064. Licensed CC0.

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