Mou Qiu-Hong, Zhang Qian, Chen Li, Dai Ying, Wei Hua, Jia Fei-Yong, Hao Yan, Li Ling, Zhang Jie, Wu Li-Jie, Ke Xiao-Yan, Yi Ming-Ji, Hong Qi, Chen Jin-Jin, Fang Shuan-Feng, Wang Yi-Chao, Wang Qi, Chen Jie, Li Ting-Yu, Yang Ting
Growth, Development and Mental Health Center of Children and Adolescents, Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, Children'S Hospital of Chongqing Medical University, Chongqing, China.
Department of developmental and behavioral pediatrics, The First Hospital of Jilin University, Changchun, China.
Child Adolesc Psychiatry Ment Health. 2025 Mar 29;19(1):35. doi: 10.1186/s13034-025-00892-7.
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.
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.
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.
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.
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).
高血清素（5-羟色胺[5-HT]）水平是自闭症谱系障碍（ASD）最可靠且经常被重复验证的生物标志物。然而，其对男性和女性自闭症核心症状的不同影响仍不明确。本研究旨在调查自闭症谱系障碍儿童血清素水平的变化，以评估和比较其对男孩和女孩核心症状及神经发育的影响。
本研究从中国13个城市招募了1457名自闭症谱系障碍儿童和1305名发育正常（TD）的对照儿童（年龄=2至7岁）。使用社会反应量表（SRS）和儿童自闭症评定量表（CARS）评估儿童的自闭症症状，使用修订版儿童神经心理与行为量表-2016（CNBS-R2016）评估其神经发育情况。通过高效液相色谱-串联质谱法测定血清5-HT水平。
在患有自闭症谱系障碍的男孩中，血清5-HT水平升高与SRS和CARS高分以及CNBS-R2016中的沟通警示行为相关。相反，在一般、语言、大运动、适应性行为和个人社交商数方面的得分出现了相应下降。值得注意的是，患有自闭症谱系障碍的女孩中未发现差异。
与发育正常儿童相比，自闭症谱系障碍儿童，尤其是男孩，血清5-HT水平更高。此外，血清5-HT含量升高与自闭症谱系障碍男孩的核心症状显著正相关，与神经发育负相关。总体而言，本研究突出了自闭症谱系障碍患者在血清5-HT水平方面的性别差异，强调了其以性别特异性方式对自闭症谱系障碍患病率的影响。
本研究已获得重庆医科大学附属儿童医院伦理委员会批准（批准文号：(2018)IRB(STUDY)NO.121）。此外，本研究已在中国临床试验注册中心注册（注册号：ChiCTR2000031194）。
