Early-Life Critical Windows of Susceptibility to Manganese Exposure and Sex-Specific Changes in Brain Connectivity in Late Adolescence

Rechtman, Elza; Navarro, Esmeralda Álvarez; Water, Erik de; Tang, Cheuk Y.; Curtin, Paul; Papazaharias, Demetrios M.; Ambrosi, Claudia; Mascaro, Lorella; Cagna, Giuseppa; Gasparotti, Roberto; Invernizzi, Azzurra; Reichenberg, Abraham; Austin, Christine; Arora, Manish; Smith, Donald R.; Lucchini, Roberto; Wright, Robert O.; Placidi, Donatella; Horton, Megan

doi:10.1016/j.bpsgos.2022.03.016

Cited by 8 publications

(3 citation statements)

References 102 publications

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“…However, prior epidemiological evidence supports that metal mixtures are associated with changes in other neurodevelopmental domains (e.g., other aspects of cognition, behavior, and mental health), with variability in direction and magnitude of associations depending on sex, exposure timing, and the neurobehavioral domain that was examined. 1 , 50 , 63 , 89 , 90 In addition, toxicological evidence suggests that metals may act jointly on motor function. 39 , 60 In an experimental study, adult rats were dosed with either Pb, Mn, arsenic (As), or a mixture of all 3 metals, and motor function was evaluated using an open-field apparatus.…”

Section: Discussionmentioning

confidence: 99%

“… 1 , 39 , 60 , 121 We are also unable to examine and adjust for metal exposures in early life, which have been shown to be associated with brain structure and neurodevelopment in childhood and adolescence and could similarly result in residual confounding. 89 , 90 , 122 Additionally, we were unable to account for the pubertal stage as we do not have data on hormone levels or other pubertal stage assessments like Tanner stages. There may be concerns about selection bias if study participation was related to both metal exposure and motor function.…”

Section: Discussionmentioning

confidence: 99%

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Sex-specific associations of a ferroalloy metal mixture with motor function in Italian adolescents

Friedman,

Schildroth,

Fruh

et al. 2024

Environmental Epidemiology

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Background: Motor function is critical for children’s health, yet remains an understudied neurodevelopmental domain. Exposure to metals has been linked with motor function, but no study has examined the joint effects of metal mixtures. Methods: We evaluated cross-sectional associations between a metal mixture and motor function among 569 adolescents (10–14 years old) living near the ferroalloy industry. Concentrations of blood lead, hair manganese, hair copper, and hair chromium were quantified using inductively coupled plasma mass spectrometry. Neuropsychologists administered multiple fine motor function assessments: pursuit aiming, finger tapping, visual reaction time (VRT), and subtests from the Luria Nebraska battery. We estimated associations between motor function and the metal mixture using quantile-based g-computation and multivariable linear regression, adjusting for child age, sex, and socioeconomic status. We explored sex-specific associations in stratified models. Results: Associations between the metal mixture and motor function were mostly null but were modified by sex. We observed a beneficial association among females: a quartile increase in all metals in the mixture was associated with a 2.6% faster average response time on the VRT (95% confidence interval [CI] = −4.7%, −0.5%), driven by Cu and Cr. In contrast, this association was adverse among males (ß = 1.5% slower response time [95% CI = −0.7%, 3.9%]), driven by Cu and Mn. Conclusions: Results suggest that males may be more susceptible to the adverse effects of metal exposure on motor function during adolescence than females. Future studies, particularly prospective study designs, are warranted to further understand the associations of metal mixtures with motor function.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Sex-specific associations of a ferroalloy metal mixture with motor function in Italian adolescents

Friedman,

Schildroth,

Fruh

et al. 2024

Environmental Epidemiology

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“…In children, the beneficial and neurotoxic effects of Mn exposure may be unique due to the developmental timing of exposure and neuromotor function assessment (i.e., prenatal, postnatal, early childhood, childhood, adolescence, adulthood). 38 , 39 For instance, the prenatal developmental time point is considered a time point of increased demand for Mn as an essential nutrient to support healthy development of the central nervous system and fetus morphology, which is the initiation of development of neuromotor function. 3 , 9 This role of Mn as essential and neurotoxic is supported by multiple studies that found prenatal Mn exposure demonstrated an inverse U-shaped association where both low and high Mn concentrations were associated with deficits in neonatal behavioral neurological assessments at 3 d of age 40 and deficits in Bayley Scales of Infant Development (BSID)-11 measures at 6 months of age.…”

Section: Introductionmentioning

confidence: 99%

Child and Adolescent Manganese Biomarkers and Adolescent Postural Balance in Marietta CARES Cohort Participants

McBride,

Bhattacharya,

Sucharew

et al. 2024

Environ Health Perspect

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Background: Manganese (Mn) plays a significant role in both human health and global industries. Epidemiological studies of exposed populations demonstrate a dose-dependent association between Mn and neuromotor effects ranging from subclinical effects to a clinically defined syndrome. However, little is known about the relationship between early life Mn biomarkers and adolescent postural balance. Objectives: This study investigated the associations between childhood and adolescent Mn biomarkers and adolescent postural balance in participants from the longitudinal Marietta Communities Actively Researching Exposures Study (CARES) cohort. Methods: Participants were recruited into CARES when they were 7–9 y old, and reenrolled at 13–18 years of age. At both time points, participants provided samples of blood, hair, and toenails that were analyzed for blood Mn and lead (Pb), serum cotinine, hair Mn, and toenail Mn. In adolescence, participants completed a postural balance assessment. Greater sway indicates postural instability (harmful effect), whereas lesser sway indicates postural stability (beneficial effect). Multivariable linear regression models were conducted to investigate the associations between childhood and adolescent Mn biomarkers and adolescent postural balance adjusted for age, sex, height–weight ratio, parent/caregiver intelligence quotient, socioeconomic status, blood Pb, and serum cotinine. Results: CARES participants who completed the adolescent postural balance assessment ( ) were 98% White and 54% female and had a mean age of 16 y (range: 13–18 y). In both childhood and adolescence, higher Mn biomarker concentrations were significantly associated with greater adolescent sway measures. Supplemental analyses revealed sex-specific associations; higher childhood Mn biomarker concentrations were significantly associated with greater sway in females compared with males. Discussion: This study found childhood and adolescent Mn biomarkers were associated with subclinical neuromotor effects in adolescence. This study demonstrates postural balance as a sensitive measure to assess the association between Mn biomarkers and neuromotor function. https://doi.org/10.1289/EHP13381

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Environmental Toxicants and the Developing Brain

Wylie

Short

2023

Biological Psychiatry

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Early-Life Critical Windows of Susceptibility to Manganese Exposure and Sex-Specific Changes in Brain Connectivity in Late Adolescence

Cited by 8 publications

References 102 publications

Sex-specific associations of a ferroalloy metal mixture with motor function in Italian adolescents

Sex-specific associations of a ferroalloy metal mixture with motor function in Italian adolescents

Child and Adolescent Manganese Biomarkers and Adolescent Postural Balance in Marietta CARES Cohort Participants

Environmental Toxicants and the Developing Brain

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