Gender specific influence of serotonin on core symptoms and neurodevelopment of autism spectrum disorders: A multicenter study in China

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 investigat...

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Main 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
Format: Article
Language:English
Published: BMC 2025-03-01
Series:Child and Adolescent Psychiatry and Mental Health
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Online Access:https://doi.org/10.1186/s13034-025-00892-7
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author 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
author_facet 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
author_sort Qiu-hong Mou
collection DOAJ
description 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).
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spelling doaj-art-7ba461bfc39f4b33b4f6522d8ad894a22025-08-20T02:49:33ZengBMCChild and Adolescent Psychiatry and Mental Health1753-20002025-03-0119111010.1186/s13034-025-00892-7Gender specific influence of serotonin on core symptoms and neurodevelopment of autism spectrum disorders: A multicenter study in ChinaQiu-hong Mou0Qian Zhang1Li Chen2Ying Dai3Hua Wei4Fei-Yong Jia5Yan Hao6Ling Li7Jie Zhang8Li-Jie Wu9Xiao-Yan Ke10Ming-Ji Yi11Qi Hong12Jin-Jin Chen13Shuan-Feng Fang14Yi-Chao Wang15Qi Wang16Jie Chen17Ting-Yu Li18Ting Yang19Growth, 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 UniversityGrowth, 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 UniversityGrowth, 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 UniversityGrowth, 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 UniversityGrowth, 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 UniversityDepartment of developmental and behavioral pediatrics, The First Hospital of Jilin UniversityDepartment of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Children Rehabilitation, Hainan Women and Children’S Medical CenterChildren Health Care Center, Xi’an Children’S HospitalDepartment of Children’S and Adolescent Health, Public Health College of Harbin Medical UniversityChild Mental Health Research Center of Nanjing Brain HospitalDepartment of Child Health Care, The Affiliated Hospital of Qingdao UniversityMaternal and Child Health Hospital of BaoanDepartment of Child Healthcare, Shanghai Children’S Hospital, Shanghai Jiao Tong UniversityChildren’S Hospital Affiliated to Zhengzhou UniversityNHC Key Laboratory of Birth Defect for Research and Prevention, Hunan Provincial Maternal and Child Health Care HospitalDeyang Maternity & Child Healthcare HospitalGrowth, 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 UniversityGrowth, 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 UniversityGrowth, 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 UniversityAbstract 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).https://doi.org/10.1186/s13034-025-00892-7Autism spectrum disorder5-HTNeurological developmentClinical symptomsSex differences
spellingShingle 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
Gender specific influence of serotonin on core symptoms and neurodevelopment of autism spectrum disorders: A multicenter study in China
Child and Adolescent Psychiatry and Mental Health
Autism spectrum disorder
5-HT
Neurological development
Clinical symptoms
Sex differences
title Gender specific influence of serotonin on core symptoms and neurodevelopment of autism spectrum disorders: A multicenter study in China
title_full Gender specific influence of serotonin on core symptoms and neurodevelopment of autism spectrum disorders: A multicenter study in China
title_fullStr Gender specific influence of serotonin on core symptoms and neurodevelopment of autism spectrum disorders: A multicenter study in China
title_full_unstemmed Gender specific influence of serotonin on core symptoms and neurodevelopment of autism spectrum disorders: A multicenter study in China
title_short Gender specific influence of serotonin on core symptoms and neurodevelopment of autism spectrum disorders: A multicenter study in China
title_sort gender specific influence of serotonin on core symptoms and neurodevelopment of autism spectrum disorders a multicenter study in china
topic Autism spectrum disorder
5-HT
Neurological development
Clinical symptoms
Sex differences
url https://doi.org/10.1186/s13034-025-00892-7
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