Precision Medicine in Pediatric Attention-deficit/Hyperactivity Disorder: A Systematic Review of Behavioral,
Marija Pranjić1,2, Virginia Peisch1, Nikolina Vukšić1
1Division of Developmental Medicine, Boston Children's Hospital, Boston, MA; and.
Insights
Objective diagnostic markers for pediatric attention-deficit/hyperactivity disorder (ADHD) show promise. Physical activity, neuroimaging, and genetic profiles offer potential for improved ADHD diagnosis, though implementation challenges remain.
Area of Science:
- Neuroscience
- Genetics
- Developmental Pediatrics
Background:
- Attention-deficit/hyperactivity disorder (ADHD) is a prevalent childhood psychiatric condition.
- Current diagnostic methods for pediatric ADHD lack objective tools, leading to potential delays and misdiagnoses.
- There is a need for reliable biomarkers to support a precision medicine approach in ADHD diagnosis.
Purpose of the Study:
- To systematically review objective biomarkers for diagnosing pediatric ADHD.
- To evaluate the potential of behavioral, neurobiological, and genetic markers.
- To assess their utility in informing a precision medicine diagnostic framework.
Main Methods:
- Conducted a systematic review following PRISMA guidelines.
- Searched MEDLINE, PsycInfo, and Scopus databases for studies published between 2012 and 2024.
- Included studies evaluating diagnostic biomarkers for pediatric ADHD with a translational aim.
Main Results:
- 111 studies were included: 42 behavioral, 44 neuroimaging, and 25 genetic.
- Physical activity measures showed good to excellent discriminant validity.
- Neuroimaging (especially with machine learning) and genetic profiles (microRNA, methylation) demonstrated strong diagnostic potential.
Conclusions:
- Promising candidate diagnostic markers for pediatric ADHD identified across multiple domains.
- Multimethod approaches are likely to enhance diagnostic accuracy.
- Complexity and cost may limit immediate primary care implementation of precision medicine for ADHD.
Objective:
Attention-deficit/hyperactivity disorder (ADHD) is one of the most common childhood psychiatric disorders and a common presenting concern in primary and developmental pediatric care. However, objective diagnostic tools are currently not available, leading to delayed and missed diagnoses. The current systematic review aimed to determine whether objective indices can serve as diagnostic markers for pediatric ADHD.
Method:
We conducted a systematic review of objective behavioral, neurobiological, and genetic biomarkers that could inform a precision medicine approach to diagnosis of pediatric ADHD. Following the PRISMA guidelines, we searched three major databases (MEDLINE, PsycInfo, and Scopus) for articles published between 2012 and 2024 that evaluated diagnostic biomarkers with a translational aim.
Results:
A total of 111 studies met inclusion criteria, including 42 behavioral, 44 neuroimaging, and 25 genetic studies. Among behavioral studies, measures of physical activity achieved discriminant validity in the good to excellent range. Neuroimaging biomarkers were strongest when machine learning and multiple-features models were used. A particularly promising direction involved task-based NIRS paradigms targeting cognitive control. The results of the genetic studies underscored the complexity of the genetic architecture of ADHD, implicating rare and common variants, as well as epigenetic mechanisms. MicroRNA and methylation profiles demonstrated the strongest accuracy, overall.
Conclusion:
Our systematic review identified promising candidate diagnostic markers for ADHD across behavioral, neuroimaging, and genetic methods. Multimethod approaches are likely to yield the strongest diagnostic accuracy. The complexity and cost of these approaches limits potential for implementation of a precision medicine approach to pediatric ADHD diagnosis in primary care settings.
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