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Introduction <p>Attention-Deficit/Hyperactivity Disorder (ADHD) is a complex and heterogeneous neurodevelopmental disorder, characterized by symptoms of inattention and/or hyperactivity/impulsivity that present across multiple contexts. Although brain-derived neurotrophic factor (BDNF) and its precursor proBDNF are associated with the etiology of ADHD, little is known about their relation to EEG alterations, especially as they manifest differently in males and females.</p> Aim <p>To investigate sex-related differences in serum levels of BDNF, proBDNF, and the proBDNF/BDNF ratio among children with ADHD, and to examine how these biomarkers relate to EEG findings, cognitive performance, and behavioral symptoms.</p> Methods <p>Ninety children aged 4–12 years were included (60 children with ADHD and 30 healthy controls). All participants underwent IQ assessment using the Stanford–Binet Intelligence Scales, and measurement of serum BDNF, proBDNF, and the proBDNF/BDNF ratio. Participants with ADHD were further assessed using sleep EEG recording, and the Conners’ Parent Rating Scale to evaluate severity of ADHD symptoms.</p> Results <p>ADHD boys with abnormal EEG had significantly lower IQ compared to those with normal EEG and controls, whereas ADHD boys with normal EEG exhibited more severe behavioral symptoms. There were significantly reduced levels of BDNF overall in boys with ADHD compared to controls, and there was also a significant increase in the ratio between proBDNF/BDNF. Female reductions were also showed in BDNF levels, while none of the proBDNF levels, proBDNF/BDNF ratio, IQ scores, or behavioral symptoms differed significantly across EEG groups.</p> Conclusion <p>Sex differences are associated with variations in neurotrophic biomarkers and clinical presentation in ADHD. A high proBDNF/BDNF ratio in boys with ADHD may indicate that their neuroplasticity is impaired. These results underscore the value of performing sex-specific analyses in ADHD research and may inform the development of new, more individualized approaches for the diagnosis and treatment of ADHD.</p>

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Gender differences in neurotrophic biomarkers and EEG patterns in children with ADHD: a case-control study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月6日

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  • Haytham Hasan,
  • Adel F. Hashish,
  • Omneya Afify,
  • Hala M. Zeidan,
  • Mostafa M. El-Saied,
  • Ehab R. Abdelraouf

摘要

Introduction

Attention-Deficit/Hyperactivity Disorder (ADHD) is a complex and heterogeneous neurodevelopmental disorder, characterized by symptoms of inattention and/or hyperactivity/impulsivity that present across multiple contexts. Although brain-derived neurotrophic factor (BDNF) and its precursor proBDNF are associated with the etiology of ADHD, little is known about their relation to EEG alterations, especially as they manifest differently in males and females.

Aim

To investigate sex-related differences in serum levels of BDNF, proBDNF, and the proBDNF/BDNF ratio among children with ADHD, and to examine how these biomarkers relate to EEG findings, cognitive performance, and behavioral symptoms.

Methods

Ninety children aged 4–12 years were included (60 children with ADHD and 30 healthy controls). All participants underwent IQ assessment using the Stanford–Binet Intelligence Scales, and measurement of serum BDNF, proBDNF, and the proBDNF/BDNF ratio. Participants with ADHD were further assessed using sleep EEG recording, and the Conners’ Parent Rating Scale to evaluate severity of ADHD symptoms.

Results

ADHD boys with abnormal EEG had significantly lower IQ compared to those with normal EEG and controls, whereas ADHD boys with normal EEG exhibited more severe behavioral symptoms. There were significantly reduced levels of BDNF overall in boys with ADHD compared to controls, and there was also a significant increase in the ratio between proBDNF/BDNF. Female reductions were also showed in BDNF levels, while none of the proBDNF levels, proBDNF/BDNF ratio, IQ scores, or behavioral symptoms differed significantly across EEG groups.

Conclusion

Sex differences are associated with variations in neurotrophic biomarkers and clinical presentation in ADHD. A high proBDNF/BDNF ratio in boys with ADHD may indicate that their neuroplasticity is impaired. These results underscore the value of performing sex-specific analyses in ADHD research and may inform the development of new, more individualized approaches for the diagnosis and treatment of ADHD.