Abstract
IMPORTANCE: Low-level lead exposure during early brain development is associated with lower cognitive abilities and externalizing behavioral problems in children. However, the association of lead exposure with depression and anxiety remains understudied, particularly in later childhood, when these symptoms often manifest. OBJECTIVE: To examine associations between low-level, serial blood lead concentrations in children and symptoms of depression and anxiety and to investigate for periods of susceptibility. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from a prospective population of 218 caregiver-child dyads (218 children and 218 parents in the Health Outcomes and Measures of Environment [HOME] Study) recruited from 2003 to 2006 in Cincinnati, Ohio. Children and their families were followed up from the second trimester to age 12 years (2016-2019). Data were analyzed between June 2024 to November 2025. EXPOSURE: Serial blood lead concentrations in children were measured at ages 1, 2, 3, 4, 5, 8, and 12 years. MAIN OUTCOMES AND MEASURES: We measured self- and caregiver-reported child depressive and anxiety symptoms at age 12 years using the Behavioral Assessment System for Children-3 (BASC-3), Children's Depression Inventory-II (CDI-II), and Screen for Child Anxiety Related Disorders (SCARED). RESULTS: Among 218 children (121 female [55.5%]; 78 Black [35.8%] and 140 White and other race or ethnicity [64.2%]; mean [SD] age, 12.4 [0.7] years), the median (IQR; range) mean within-child blood lead concentration was 9.6 (7.8 to 12.6; 4.8 to 32.4) μg/L. Each doubling in mean childhood blood lead concentrations was associated with increased risk of elevated child-reported depressive symptoms on the BASC-3 (relative risk [RR], 1.90; 95% CI, 1.00 to 3.66; P = .05) and increased risk of child- and caregiver-reported child depressive symptoms (RR, 1.76; 95% CI, 1.12 to 2.78; P = .02). By blood lead concentration, there were increasing adjusted mean differences in self-reported BASC-3 depression scores from age 1 year (1.82; 95% CI, -1.10 to 4.74; P = .22), a nonsignificant outcome, through age 8 years (3.22; 95% CI, 0.53 to 5.90; P = .02), a significant outcome. There were no associations between blood lead concentrations and self-reported depression measured with the Children's Depression Inventory-II or anxiety measured with the SCARED. Child sex and race did not modify these associations. CONCLUSIONS AND RELEVANCE: In this study, low-level childhood blood lead concentrations were associated with self-reported depressive symptoms in later childhood, with particularly large increases in risk for exposures occurring in late childhood and early adolescence. These findings suggest that lead exposure during childhood may be associated with mental health in later childhood, highlighting the need for continued efforts to prevent lead exposure.