# Age-Specific ADHD and Internalizing/Externalizing Comorbidity in Children with Neurofibromatosis Type 1: A Multi-Site Study

## TL;DR

This study finds that children with neurofibromatosis type 1 consistently show attention and behavioral problems, with stronger links in younger children and those with a family history of the condition.

## Contribution

The study reveals age-specific patterns of ADHD symptom comorbidity and identifies familial NF1 as a risk factor for behavioral issues.

## Key findings

- Inattention and hyperactivity/impulsivity are consistently linked to internalizing and externalizing problems across childhood.
- Hyperactivity/impulsivity is more strongly linked to externalizing problems in younger children.
- Children with familial NF1 show a stronger link between inattention and externalizing problems.

## Abstract

Children with neurofibromatosis type 1 (NF1) often experience attention problems and difficulties with emotions and behavior, but little is known about how these challenges covary with age. In this study, we analyzed data of 685 observations from 455 children with NF1, ages 3 to 18, to examine how attention-deficit/hyperactivity symptoms relate to emotional and behavioral problems across childhood and adolescence. We found that inattention and hyperactivity/impulsivity symptoms were consistently linked to higher levels of internalizing problems (like anxiety and depression) and externalizing problems (like aggression). The connection between hyperactivity/impulsivity and externalizing problems was strongest in younger children. Children with a family history of NF1 showed a stronger link between inattention and externalizing problems. These findings highlight the importance of monitoring attention and behavioral difficulties in children with NF1 and suggest that children with familial NF1 may benefit from early, targeted support.

Objective: The current study tested (1) how ADHD symptoms and internalizing or externalizing problems covaried across ages 3–18 in children with neurofibromatosis type 1 (NF1), and (2) whether demographic and NF1-specific factors moderated the associations. Method: We analyzed integrated cross-sectional data of 685 observations from 455 children and adolescents with NF1 (Mage = 9.79 years, SD = 3.88; 43% female) across six institutions in the United States and Australia. ADHD symptoms (inattention and hyperactivity/impulsivity) and internalizing/externalizing problems were assessed via parent-report measures. Time-varying effect modeling was employed to examine the age-specific associations between ADHD symptoms and internalizing/externalizing problems. Moderation analyses tested effects of sex, parental education, and NF1 inheritance mode (familial vs. sporadic). Results: Inattention and hyperactivity/impulsivity symptoms were associated with greater internalizing and externalizing problems across ages 3–17. Inattention links were similar across ages, while the hyperactivity/impulsivity-externalizing link was stronger in early childhood than during adolescence. NF1 inheritance mode significantly moderated the inattention-externalizing link, with stronger associations observed among children with familial NF1. Other moderators were nonsignificant. Conclusions: ADHD symptoms are robustly linked to internalizing and externalizing problems from childhood to middle adolescence in children with NF1, with familial NF1 emerging as a potentially elevated risk factor. Future longitudinal and experimental research is needed to inform integrated intervention approaches, especially for those with familial NF1.