Internalizing and externalizing symptoms in individuals with neurofibromatosis type 1: a systematic review and meta-analysis

Dan Liu, Liyan Yu, Xian Wu, Julia Moreira, Benjamin Felipe Mujica, Elora Shelly Mukhopadhyay, Angelena Novotney, André B. Rietman, Yang Hou*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)
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Abstract

BACKGROUND: 

Individuals with neurofibromatosis type 1 (NF1) frequently report psychosocial problems, among which internalizing and externalizing symptoms are the most poorly understood due to limited research and inconsistent evidence. This hinders the overall attendance of their psychosocial needs and has a major impact on their quality of life. Thus, this systematic review and meta-analysis was conducted to synthesize existing findings on the degree to which individuals with NF1 experience internalizing and externalizing symptoms, compared with the unaffected population, and explore moderators of the group disparities. 

METHODS: 

Scopus, PsycINFO, Web of Science, PubMed, and ProQuest were searched from inception to March 26th, 2024, which identified 59 eligible studies (N of NF1 = 3182, mean ages 2.38 to 46.4 years). Hedges' g was calculated for differences in internalizing and externalizing symptoms between the NF1 group and the unaffected controls. Study effect sizes were pooled using robust variance estimation and random-effects models. Moderators of group differences were tested using meta-regression. 

RESULTS: 

Random-effects meta-analyses indicated that compared with unaffected controls, individuals with NF1 showed more severe depressive (k = 21; g = 0.43; 95% CI [0.21, 0.65]), anxiety (k = 24; g = 0.27; 95% CI [0.01, 0.54]), somatic (k = 27; g = 0.56; 95% CI [0.30, 0.83]), total internalizing (k = 75; g = 0.50; 95% CI [0.33, 0.67]), aggression (k = 33; g = 0.33; 95% CI [0.08, 0.58]), delinquency, (k = 37; g = 0.43; 95% CI [0.26, 0.60]), and total externalizing symptoms (k = 47; g = 0.24; 95% CI [0.13, 0.35]). Studies that included more participants with NF1 who had ADHD or a lower verbal IQ reported greater group disparities in total internalizing symptoms or aggression. 

CONCLUSIONS: 

Findings highlight the importance of promptly recognizing internalizing and externalizing symptoms in individuals with NF1 for timely interventions. Future research should identify predictors of internalizing and externalizing symptoms within the NF1 population to inform our knowledge and intervention development. Other implications for future research were also discussed. SYSTEMATIC REVIEW REGISTRATION: The study protocol of this meta-analysis was registered at PROSPERO (CRD42023478258).

Original languageEnglish
Article number20
Pages (from-to)20
Number of pages1
JournalSystematic Reviews
Volume14
Issue number1
DOIs
Publication statusPublished - Dec 2025

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© The Author(s) 2025.

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