Kelly J Brunst1, Patrick H Ryan2, Mekibib Altaye2, Kimberly Yolton3, Thomas Maloney4, Travis Beckwith4, Grace LeMasters5, Kim M Cecil6. 1. Department of Environmental Health, University of Cincinnati, 160 Panzeca Way, ML 0056, Cincinnati, OH, 45267, USA. Electronic address: kelly.brunst@uc.edu. 2. Department of Environmental Health, University of Cincinnati, 160 Panzeca Way, ML 0056, Cincinnati, OH, 45267, USA; Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 7035, Cincinnati, OH, 45229, USA. 3. Division of General and Community Pediatrics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, 3333 Burnet Avenue, MLC, 5041, Cincinnati, OH, USA. 4. Imaging Research Center, Department of Radiology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, ML 5033, Cincinnati, OH, 45229, USA. 5. Department of Environmental Health, University of Cincinnati, 160 Panzeca Way, ML 0056, Cincinnati, OH, 45267, USA. 6. Department of Environmental Health, University of Cincinnati, 160 Panzeca Way, ML 0056, Cincinnati, OH, 45267, USA; Imaging Research Center, Department of Radiology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, ML 5033, Cincinnati, OH, 45229, USA.
Abstract
BACKGROUND: Exposure to traffic-related air pollution (TRAP) has been linked to childhood anxiety symptoms. Neuroimaging in patients with anxiety disorders indicate altered neurochemistry. OBJECTIVES: Evaluate the impact of TRAP on brain metabolism and its relation to childhood anxiety symptoms in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS). METHODS: Adolescents (n = 145) underwent magnetic resonance spectroscopy. Brain metabolites, including myo-inositol, N-acetylaspartate, creatine, choline, glutamate, glutamate plus glutamine, and glutathione were measured in the anterior cingulate cortex. Anxiety symptoms were assessed using the Spence Children's Anxiety Scale. TRAP exposure in early-life, averaged over childhood, and during the 12 months prior to imaging was estimated using a validated land use regression model. Associations between TRAP exposure, brain metabolism, and anxiety symptoms were estimated using linear regression and a bootstrapping approach for testing mediation by brain metabolite levels. RESULTS: Recent exposure to high levels of TRAP was associated with significant increases in myo-inositol (β = 0.26; 95%CI 0.01, 0.51) compared to low TRAP exposure. Recent elevated TRAP exposure (β = 4.71; 95% CI 0.95, 8.45) and increased myo-inositol levels (β = 2.98; 95% CI 0.43, 5.52) were also significantly associated with increased generalized anxiety symptoms with 12% of the total effect between TRAP and generalized anxiety symptoms being mediated by myo-inositol levels. CONCLUSIONS: This is the first study of children to utilize neuroimaging to link TRAP exposure, metabolite dysregulation in the brain, and generalized anxiety symptoms among otherwise healthy children. TRAP may elicit atypical excitatory neurotransmission and glial inflammatory responses leading to increased metabolite levels and subsequent anxiety symptoms.
BACKGROUND: Exposure to traffic-related air pollution (TRAP) has been linked to childhood anxiety symptoms. Neuroimaging in patients with anxiety disorders indicate altered neurochemistry. OBJECTIVES: Evaluate the impact of TRAP on brain metabolism and its relation to childhood anxiety symptoms in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS). METHODS: Adolescents (n = 145) underwent magnetic resonance spectroscopy. Brain metabolites, including myo-inositol, N-acetylaspartate, creatine, choline, glutamate, glutamate plus glutamine, and glutathione were measured in the anterior cingulate cortex. Anxiety symptoms were assessed using the Spence Children's Anxiety Scale. TRAP exposure in early-life, averaged over childhood, and during the 12 months prior to imaging was estimated using a validated land use regression model. Associations between TRAP exposure, brain metabolism, and anxiety symptoms were estimated using linear regression and a bootstrapping approach for testing mediation by brain metabolite levels. RESULTS: Recent exposure to high levels of TRAP was associated with significant increases in myo-inositol (β = 0.26; 95%CI 0.01, 0.51) compared to low TRAP exposure. Recent elevated TRAP exposure (β = 4.71; 95% CI 0.95, 8.45) and increased myo-inositol levels (β = 2.98; 95% CI 0.43, 5.52) were also significantly associated with increased generalized anxiety symptoms with 12% of the total effect between TRAP and generalized anxiety symptoms being mediated by myo-inositol levels. CONCLUSIONS: This is the first study of children to utilize neuroimaging to link TRAP exposure, metabolite dysregulation in the brain, and generalized anxiety symptoms among otherwise healthy children. TRAP may elicit atypical excitatory neurotransmission and glial inflammatory responses leading to increased metabolite levels and subsequent anxiety symptoms.
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