Systematic Review and Meta-Analysis: Attention-Deficit/Hyperactivity Disorder Symptoms in Children With Neurofibromatosis Type 1.
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OBJECTIVE: This meta-analysis aimed to robustly estimate differences in attention-deficit/hyperactivity disorder (ADHD) symptoms between children and adolescents with and without neurofibromatosis type 1 (NF1). METHOD: Systematic literature searches were conducted in Scopus, PsycINFO, Web of Science, PubMed, and ProQuest in September 2022, with a supplemental search conducted in Google Scholar in February 2023. The searches identified 2,153 unique articles. Screening identified 114 academic journal articles that assessed parent/caregiver- or teacher-reported ADHD symptoms for children/adolescents with NF1. Two researchers independently screened articles and extracted data. The primary outcome was group differences in ADHD symptoms between children/adolescents with and without NF1 (Hedges g). Data were analyzed using robust variance estimation and random-effects models. RESULTS: The meta-analysis included 70 studies (138 effect sizes), involving 3,653 children/adolescents with NF1 (46% female; mean age = 9.69 years, SD = 2.60 years) and 4,895 children/adolescents without NF1 (48% female; mean age = 10.03 years, SD = 3.10 years). According to parent/caregiver reports, children/adolescents with NF1 exhibited more severe inattentive symptoms (g = 1.20; 95% CI = 1.06-1.35), hyperactive/impulsive symptoms (g = 0.85; 95% CI = 0. 68-1.03), and combined ADHD symptoms (g = 1.02; 95% CI = 0.87-1.17) than unaffected controls. Inattentive ADHD symptoms were more elevated than hyperactivity/impulsivity for children/adolescents with NF1. Larger effect sizes for inattention and hyperactivity/impulsivity were associated with older age, lower intelligence quotient (IQ), and parent/caregiver vs teacher reports. CONCLUSION: NF1 is a monogenic condition that has strong associations with elevated ADHD symptoms. Findings highlight the importance of early intervention and targeted support for ADHD-related problems in children with NF1. PLAIN LANGUAGE SUMMARY: Increasing evidence has suggested a higher risk for attention-deficit/hyperactivity disorder (ADHD) in individuals with neurofibromatosis type 1 (NF1). In this study of ADHD symptom severity in youth with NF1, the authors analyzed data from 70 articles. The authors found much more severe ADHD symptoms in children and adolescents with NF1 compared to youth without NF1. Inattentive symptoms were more pronounced in children with NIF who were older or had a lower IQ. STUDY PREREGISTRATION INFORMATION: Compare the ADHD problems between NF1 and control groups; https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=462063.