Qiu-Hong Mou, Qian Zhang, Li Chen, Ying Dai, Hua Wei, Fei-Yong Jia, Yan Hao, Ling Li, Jie Zhang, Li-Jie Wu, Xiao-Yan Ke, Ming-Ji Yi, Qi Hong, Jin-Jin Chen, Shuan-Feng Fang, Yi-Chao Wang, Qi Wang, Jie Chen, Ting-Yu Li, Ting Yang
{"title":"Gender specific influence of serotonin on core symptoms and neurodevelopment of autism spectrum disorders: A multicenter study in China.","authors":"Qiu-Hong Mou, Qian Zhang, Li Chen, Ying Dai, Hua Wei, Fei-Yong Jia, Yan Hao, Ling Li, Jie Zhang, Li-Jie Wu, Xiao-Yan Ke, Ming-Ji Yi, Qi Hong, Jin-Jin Chen, Shuan-Feng Fang, Yi-Chao Wang, Qi Wang, Jie Chen, Ting-Yu Li, Ting Yang","doi":"10.1186/s13034-025-00892-7","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p><p><strong>Trial registration: </strong>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).</p>","PeriodicalId":9934,"journal":{"name":"Child and Adolescent Psychiatry and Mental Health","volume":"19 1","pages":"35"},"PeriodicalIF":3.4000,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Child and Adolescent Psychiatry and Mental Health","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13034-025-00892-7","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PEDIATRICS","Score":null,"Total":0}
引用次数: 0
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).
期刊介绍：
Child and Adolescent Psychiatry and Mental Health, the official journal of the International Association for Child and Adolescent Psychiatry and Allied Professions, is an open access, online journal that provides an international platform for rapid and comprehensive scientific communication on child and adolescent mental health across different cultural backgrounds. CAPMH serves as a scientifically rigorous and broadly open forum for both interdisciplinary and cross-cultural exchange of research information, involving psychiatrists, paediatricians, psychologists, neuroscientists, and allied disciplines. The journal focusses on improving the knowledge base for the diagnosis, prognosis and treatment of mental health conditions in children and adolescents, and aims to integrate basic science, clinical research and the practical implementation of research findings. In addition, aspects which are still underrepresented in the traditional journals such as neurobiology and neuropsychology of psychiatric disorders in childhood and adolescence are considered.
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