**Background:** Anxiety disorders affect 7%–10% of children and adolescents and are the most common mental health conditions across the lifespan. They frequently emerge in late childhood and adolescence and are associated with significant impairment, increased risk of mood disorders, substance misuse, suicidal behavior, and economic disadvantage. While psychological, biological, and developmental risk factors for anxiety are well-characterized, the role of environmental toxicants—particularly those encountered during fetal development—remains poorly understood. Polybrominated diphenyl ethers (PBDEs) are flame retardant additives widely used in consumer products; they are lipophilic, cross the placenta, and persist in human tissue for up to a decade. Prior research has linked PBDE exposure to cognitive deficits, ADHD symptoms, and behavioral dysregulation, but no studies had examined their relationship with anxiety symptoms in adolescence—a critical period when anxiety disorders frequently emerge.
**Methods:** The study utilized data from the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort that enrolled 468 pregnant women at 16 ± 3 weeks of gestation from 2003 to 2006 from 9 prenatal clinics in the greater Cincinnati, Ohio area. The final analytic sample included 236 adolescents (55.9% female; mean age 12.4 ± 0.7 years) with complete maternal PBDE measurements and 12-year follow-up data. Maternal serum concentrations of five PBDE congeners (PBDE-28, -47, -99, -100, and -153) were measured using gas chromatography/isotope dilution high-resolution mass spectrometry and standardized by serum total lipid concentrations. PBDE-47 was the most abundant congener (geometric mean: 20.8 ng/g lipid). Anxiety symptoms were assessed using the self-report Screen for Child Anxiety Related Emotional Disorders (SCARED), a 41-item measure yielding total and five subscale scores (generalized anxiety, social phobia, separation anxiety, somatic symptoms/panic, school phobia). Depressive symptoms were measured using the Children's Depression Inventory 2nd Edition (CDI-2). Multivariable linear regression and modified Poisson regression were used to estimate associations, adjusting for child sex, maternal race, maternal age at delivery, maternal marital status, maternal education, household income, maternal depressive and anxiety symptoms (SCL-90), and relational frustration (BASC-3 PRQ). Sensitivity analyses additionally adjusted for maternal blood lead and mercury concentrations.
**Key Results:** Total SCARED scores ranged from 0 to 65 (mean: 21.1 ± 12.5) and were higher in females (23.2 ± 13.7) than males (18.4 ± 10.4). Thirty-five percent of adolescents had SCARED total scores above the clinically significant cutoff (≥25). After covariate adjustment, each doubling in maternal PBDE concentrations was significantly associated with increased SCARED total scores: PBDE-28 (β = 2.1, 95% CI: 0.7–3.5, p = .004), PBDE-47 (β = 1.6, 95% CI: 0.4–2.8, p = .008), PBDE-99 (β = 1.7, 95% CI: 0.5–2.9, p = .004), and ∑PBDE (β = 1.6, 95% CI: 0.3–2.9, p = .019). Associations for PBDE-100 (β = 0.9, 95% CI: −0.2–2.0, p = .116) and PBDE-153 (β = 0.4, 95% CI: −0.7–1.5, p = .451) were positive but not statistically significant. Higher PBDE concentrations were consistently associated with increased relative risk of clinically significant SCARED total scores (≥25): PBDE-28 (RR: 1.26, 95% CI: 1.11–1.42, p < .001), PBDE-47 (RR: 1.20, 95% CI: 1.07–1.33, p < .001), PBDE-99 (RR: 1.18, 95% CI: 1.07–1.30, p = .001), PBDE-100 (RR: 1.13, 95% CI: 1.01–1.26, p = .027), and ∑PBDE (RR: 1.19, 95% CI: 1.06–1.33, p = .002). Associations were strongest for panic and separation anxiety subscales. For depressive symptoms, each doubling of PBDE-28 was associated with increased CDI-2 total T-scores (β = 1.5, 95% CI: 0.4–2.6, p = .007), but other congeners and ∑PBDE showed non-significant positive associations (e.g., for ∑PBDE, CDI total β = 0.8, 95% CI: −0.2–1.8, p = .11). Results were robust to sensitivity analyses excluding extreme PBDE values, excluding twins, and adjusting for lead and mercury. No significant PBDE-by-sex interactions were detected.
**Clinical Implications:** This is the first study to demonstrate a prospective association between gestational PBDE exposure and anxiety symptoms in adolescence. The findings extend the known neurodevelopmental effects of PBDEs beyond cognitive deficits and ADHD to include internalizing symptoms, specifically anxiety. The associations were observed at PBDE concentrations typical of the general US population during the study period, and the effects were clinically meaningful—each doubling of PBDE concentration increased the risk of clinically significant anxiety by 19%–26%. Given that PBDEs persist in the environment and remain present in homes and offices despite being phased out of production in 2004, these findings have important public health implications. The study highlights the need for continued monitoring of PBDE exposure and its neurodevelopmental consequences, particularly during sensitive developmental windows such as mid-pregnancy when active neurogenesis, synaptogenesis, and myelination are occurring in cortical and limbic brain regions. Limitations include the single-site design with limited racial/ethnic diversity, reliance on self-report measures rather than clinician-administered diagnostic assessments, assessment at a single time point (age 12), and inability to determine whether symptoms represent threshold psychiatric disorders. Future research should examine the persistence of these associations into later adolescence and adulthood, investigate potential mechanisms including effects on prefrontal-limbic circuitry, and evaluate whether reducing PBDE exposure could lower the population burden of anxiety disorders.