Lisa B Rokoff1, Jessica R Shoaff2, Brent A Coull3, Michelle Bosquet Enlow4, David C Bellinger5, Susan A Korrick6. 1. Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Population Health Sciences Program, Harvard University, Cambridge, MA, USA. Electronic address: lrokoff@mail.harvard.edu. 2. Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 3. Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 4. Department of Psychiatry and Behavioral Sciences, Boston Children's Hospital, Department of Psychiatry, Harvard Medical School, Boston, MA, USA. 5. Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. 6. Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Abstract
BACKGROUND: Although prenatal chemical exposures influence neurobehavior, joint exposures are not well explored as risk factors for internalizing disorders through adolescence. OBJECTIVE: To evaluate associations of prenatal organochlorine and metal exposures, considered individually and as a mixture, with mid-childhood and adolescent internalizing symptoms. METHODS: Participants were 468 children from a prospective cohort recruited at birth (1993-1998) in New Bedford, Massachusetts. Organochlorines (hexachlorobenzene, p,p'-dichlorodiphenyl dichloroethylene, polychlorinated biphenyls) and metals (lead, manganese) were analyzed in cord blood. Internalizing symptoms (anxiety, depressive, somatic) were assessed via multiple informants on the Conners' Rating Scale (CRS) at 8-years and Behavior Assessment System for Children, Second Edition (BASC-2) at 15-years; higher T-scores indicate greater symptoms. Overall and sex-specific covariate-adjusted associations were evaluated using Bayesian Kernel Machine Regression (BKMR) and five-chemical linear regression models. RESULTS: The cohort was socioeconomically diverse (35% household income <$20,000; 55% maternal ≤ high school education at birth). Most chemical concentrations were consistent with background levels [e.g., median (range) cord blood lead: 1.1 (0-9.4) μg/dL]. BKMR suggested linear associations and no interactions between chemicals. The overall mixture was positively associated with Conners' Parent Rating Scale (CPRS) and BASC-2 Self Report of Personality (SRP) anxiety and depressive symptoms, and negatively with somatic symptoms. Prenatal lead was positively associated with adolescent anxiety symptoms [1.56 (95% CI: 0.50, 2.61) BASC-2 SRP Anxiety score increase per doubling lead]. For CRPS and BASC-2 SRP, a doubling of cord blood manganese was positively associated with internalizing symptoms for girls [e.g., 3.26 (95% CI: 0.27, 6.25) BASC-2 SRP Depression score increase], but not boys. Organochlorine exposures were not adversely associated with internalizing symptoms. DISCUSSION: Low-level prenatal lead exposure was positively associated with adolescent anxiety symptoms, and prenatal manganese exposure was positively associated with internalizing symptoms for girls from mid-childhood through adolescence. In utero neurotoxicant metal exposures may contribute to the emergence of anxiety and depression.
BACKGROUND: Although prenatal chemical exposures influence neurobehavior, joint exposures are not well explored as risk factors for internalizing disorders through adolescence. OBJECTIVE: To evaluate associations of prenatal organochlorine and metal exposures, considered individually and as a mixture, with mid-childhood and adolescent internalizing symptoms. METHODS: Participants were 468 children from a prospective cohort recruited at birth (1993-1998) in New Bedford, Massachusetts. Organochlorines (hexachlorobenzene, p,p'-dichlorodiphenyl dichloroethylene, polychlorinated biphenyls) and metals (lead, manganese) were analyzed in cord blood. Internalizing symptoms (anxiety, depressive, somatic) were assessed via multiple informants on the Conners' Rating Scale (CRS) at 8-years and Behavior Assessment System for Children, Second Edition (BASC-2) at 15-years; higher T-scores indicate greater symptoms. Overall and sex-specific covariate-adjusted associations were evaluated using Bayesian Kernel Machine Regression (BKMR) and five-chemical linear regression models. RESULTS: The cohort was socioeconomically diverse (35% household income <$20,000; 55% maternal ≤ high school education at birth). Most chemical concentrations were consistent with background levels [e.g., median (range) cord blood lead: 1.1 (0-9.4) μg/dL]. BKMR suggested linear associations and no interactions between chemicals. The overall mixture was positively associated with Conners' Parent Rating Scale (CPRS) and BASC-2 Self Report of Personality (SRP) anxiety and depressive symptoms, and negatively with somatic symptoms. Prenatal lead was positively associated with adolescent anxiety symptoms [1.56 (95% CI: 0.50, 2.61) BASC-2 SRP Anxiety score increase per doubling lead]. For CRPS and BASC-2 SRP, a doubling of cord blood manganese was positively associated with internalizing symptoms for girls [e.g., 3.26 (95% CI: 0.27, 6.25) BASC-2 SRP Depression score increase], but not boys. Organochlorine exposures were not adversely associated with internalizing symptoms. DISCUSSION: Low-level prenatal lead exposure was positively associated with adolescent anxiety symptoms, and prenatal manganese exposure was positively associated with internalizing symptoms for girls from mid-childhood through adolescence. In utero neurotoxicant metal exposures may contribute to the emergence of anxiety and depression.
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