Interrelation between homocysteine metabolism and the development of autism spectrum disorder in children

Bingbing Li; Yiran Xu; Dizhou Pang; Qiang Zhao; Lingling Zhang; Ming Li; Wenhua Li; Guiqin Duan; Changlian Zhu

doi:10.3389/fnmol.2022.947513

Interrelation between homocysteine metabolism and the development of autism spectrum disorder in children

Front Mol Neurosci. 2022 Aug 15:15:947513. doi: 10.3389/fnmol.2022.947513. eCollection 2022.

Authors

Bingbing Li¹, Yiran Xu¹, Dizhou Pang², Qiang Zhao³, Lingling Zhang¹, Ming Li¹, Wenhua Li¹, Guiqin Duan², Changlian Zhu^{1

4}

Affiliations

¹ Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, Third Affiliated Hospital and Institute of Neuroscience, Zhengzhou University, Zhengzhou, China.
² Center for Child Behavioral Development, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
³ Key Clinical Laboratory of Henan Province, Department of Clinical Laboratory, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
⁴ Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Sahlgrenska Academy, Gothenburg, Sweden.

Abstract

Evidence is emerging that dysregulation of circulating concentrations of homocysteine, an important intermediate in folate and vitamin B12 metabolism, is associated with autism spectrum disorder (ASD), but comprehensive assessments and correlations with disease characteristics have not been reported. Multivariate ordinal regression and restricted cubic spline (RCS) models were used to estimate independent correlations between serum homocysteine, folate, and vitamin B12 levels and clinical outcomes and severity of children with ASD. After adjusting for confounding factors, serum homocysteine levels were significantly higher in children with ASD than in healthy controls (β: 0.370; 95% CI: 0.299~0.441, p < 0.001). Moreover, homocysteine had a good diagnostic ability for distinguishing children with ASD from healthy subjects (AUC: 0.899, p < 0.001). The RCS model indicated a positive and linear association between serum homocysteine and the risk of ASD. The lowest quartile of folate was positively associated with ASD severity (OR: 4.227, 95% CI: 1.022~17.488, p = 0.041) compared to the highest quartile, and serum folate showed a negative and linear association with ASD severity. In addition, decreased concentrations of folate and vitamin B12 were associated with poor adaptive behavior developmental quotients of the Gesell Developmental Schedules (p < 0.05). Overall, an increased homocysteine level was associated with ASD in a linear manner and is thus a novel diagnostic biomarker for ASD. Decreased concentrations of folate and vitamin B12 were associated with poor clinical profiles of children with ASD. These findings suggest that homocysteine-lowering interventions or folate and vitamin B12 supplementation might be a viable treatment strategy for ASD.

Keywords: autism spectrum disorder; biomarkers; folate; homocysteine; vitamin B12.