Abstract
BACKGROUND: High serotonin (5-hydroxytryptamine [5-HT]) blood levels are the most reliable and frequently replicated biomarker for autism spectrum disorders (ASDs). However, their differential influence on core ASD symptoms in males and females remains unclear. This study aimed to investigate the changes in 5-HT levels in children with ASD to assess and compare its influence on the core symptoms and neurodevelopment of boys and girls. METHODS: Herein, 1,457 ASD children and 1,305 typically developing (TD) controls (age = 2-7 years) were enrolled from 13 cities across China. Social Responsiveness Scale (SRS) and Childhood Autism Rating Scale (CARS) were used to evaluate the ASD symptoms in children, and the revised Children Neuropsychological and Behavior Scale-Revision 2016 (CNBS-R2016) was used to evaluate their neurodevelopment. The 5-HT serum levels were measured by high-performance liquid chromatography-tandem mass spectrometry. RESULTS: In boys with ASD, increased serum 5-HT levels correlated with high scores on SRS and CARS and with communication warning behavior of CNBS-R2016. Conversely, concomitant decline was observed in the scores on the general, language, gross motor, adaptive behavior, and personal-social quotients. Notably, no differences were found in girls with ASD. CONCLUSIONS: Children with ASD, especially boys, presented higher serum 5-HT levels compared with TD children. Additionally, increased 5-HT content is considerably positively associated with core ASD symptoms and negatively associated with neurodevelopment in boys with ASD. Overall, this study highlights the gender bias in patients with ASD regarding 5-HT serum levels, underscoring its influence on ASD prevalence in a sex-specific manner. TRIAL REGISTRATION: This study has been approved by the Ethics Committee of the Children's Hospital of Chongqing Medical University (approval number: (2018) IRB (STUDY) NO.121). Additionally, this study is registered with the China Clinical Trial Registry (Registration Number: ChiCTR2000031194).