# Longitudinal study of metal mixtures and the developmental origins of adolescent risk-taking > **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $786,794 ## Abstract 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... ## Key facts - **NIH application ID:** 10981029 - **Project number:** 2R01ES028927-06A1 - **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI - **Principal Investigator:** Megan K Horton - **Activity code:** R01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $786,794 - **Award type:** 2 - **Project period:** 2018-09-30 → 2029-06-30 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10981029 ## Citation > US National Institutes of Health, RePORTER application 10981029, Longitudinal study of metal mixtures and the developmental origins of adolescent risk-taking (2R01ES028927-06A1). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10981029. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*