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Longitudinal study of metal mixtures and the developmental origins of adolescent risk-taking

Award Number: R01ES028927
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/30/2018
PERIOD OF PERFORMANCE END DATE: 06/30/2029

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Longitudinal study of metal mixtures and the developmental origins of adolescent risk-taking - Abstract Risk-taking is a critical component of adolescence, yet maladaptive or unhealthy risk-taking during this developmental period is associated with significant adolescent morbidity and mortality. While research has linked early-life environmental exposures to maladaptive neurobehavioral phenotypes, little is known about the developmental trajectories that contribute to risk-taking. Because brain development is dynamic and nonlinear throughout adolescence, research needs to assess phenotypic developmental trajectories over time rather than at a single timepoint—however, such research is challenging, time-intensive, and costly. We can overcome these challenges with our Programming Research in Obesity, GRowth, Environment and Social Stressors (PROGRESS) cohort, which has collected longitudinal data on metal exposures as well as neural and behavioral outcomes from pregnancy through childhood and into adolescence. In our first grant cycle, we linked reconstructed early-life metal exposure data from our novel tooth biomarker with a single timepoint of multi-modal magnetic resonance imaging (MRI) scans and neuropsychological assessments to demonstrate that a mixture of lead, manganese, and zinc exposure at 6–9 postnatal months increased internalizing behaviors and impacted neural activity in brain areas subserving emotional processing in preadolescent children. Increased internalizing problems in childhood may increase the risk for maladaptive risk-taking behaviors in adolescence. Thus, we hypothesize that early-life exposure to neuroactive metals may impact the trajectory of brain and behavioral development related to risk-taking. In this first renewal application, we propose to extend our study in the PROGRESS cohort to include longitudinal assessments of brain structure and function, allowing us to investigate the impact of early-life metal exposures on developmental trajectories of adolescent risk-taking behaviors. We propose an accelerated longitudinal design to shorten the time needed to assess neurodevelopmental trajectories compared to a traditional longitudinal cohort. Our design leverages existing baseline multi-modal MRI and performative assessments of risk-taking collected in the first cycle (ages 8–14) and adds follow-up of these assessments in the new cycle. We also will enroll new PROGRESS participants (ages 16–22), allowing us to assess phenotypic trajectories from age 8–22 years—thus covering all of adolescence. For all participants, we will collect self-reported assessments of risk-taking behavior in adolescence. This renewal builds on our prior cross-sectional and prospective findings by creating a lifecourse study of adolescent developmental trajectories of brain structure/function and risk-taking spanning more than 20 years in a single grant cycle. Our approach will serve as a model for future studies of early-life environment and adolescent health, an understudied life stage representing the transition into adulthood. We will determine critical windows for early-life metal exposures on adolescent developmental trajectories of risk-taking, which are key to applying interventions at the appropriate age to promote optimal development and improved health.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $706,587 )
2025	2025	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Environmental Health	001	7	8/8/2025	NON-COMPETING CONTINUATION	$492,567
2025	2025	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Environmental Health	002	7	8/12/2025	SUPPLEMENT FOR EXPANSION	$64,681
2025	2025	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Environmental Health	003	7	8/13/2025	SUPPLEMENT FOR EXPANSION	$149,339
2025	2022	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Environmental Health	000	5	3/6/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $706,587

Issue Date FY: 2024 ( Subtotal = $786,794 )
2024	2024	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Environmental Health	000	6	9/13/2024	COMPETING CONTINUATION	$786,794
														Subtotal = $786,794

Issue Date FY: 2022 ( Subtotal = $620,212 )
2022	2022	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Environmental Health	000	5	8/19/2022	NON-COMPETING CONTINUATION	$620,212
														Subtotal = $620,212

Issue Date FY: 2021 ( Subtotal = $601,175 )
2021	2021	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Environmental Health	000	4	8/17/2021	NON-COMPETING CONTINUATION	$601,175
2021	2021	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Environmental Health	001	4	9/6/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $601,175

Issue Date FY: 2020 ( Subtotal = $601,175 )
2020	2020	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Environmental Health	000	3	8/24/2020	NON-COMPETING CONTINUATION	$601,175
														Subtotal = $601,175

Issue Date FY: 2019 ( Subtotal = $601,175 )
2019	2019	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Environmental Health	001	2	9/13/2019	NON-COMPETING CONTINUATION	$601,175
2019	2018	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Environmental Health	000	1	8/5/2019	NEW	$0
														Subtotal = $601,175

Issue Date FY: 2018 ( Subtotal = $657,933 )
2018	2018	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Environmental Health	000	1	9/21/2018	NEW	$657,933
														Subtotal = $657,933

Grand Total All Awards = $4,575,051

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Longitudinal study of metal mixtures and the developmental origins of adolescent risk-taking

Award Number: R01ES028927

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/30/2018

PERIOD OF PERFORMANCE END DATE: 06/30/2029

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