Background. Children with Tuberous Sclerosis Complex (TSC) are at a high risk for an intellectual impairment and experiencing psychiatric symptoms. Internalizing problems, such as anxiety and a...Show moreBackground. Children with Tuberous Sclerosis Complex (TSC) are at a high risk for an intellectual impairment and experiencing psychiatric symptoms. Internalizing problems, such as anxiety and a depressed mood, are among the most prevalent reported psychiatric symptoms in patients with TSC. These problems often precede more severe psychopathology, especially when they remain unrecognized. Despite this, research on this subject is still remarkably scarce, especially in children. A factor that seems to be positively associated with internalizing problems is intellectual ability. A major research question that arises is whether more internalizing problems are related to higher intelligence levels in children with TSC, which was examined in the current study. As TSC1 is related to less (severe) intellectual impairments compared to TSC2, a differentiation was made between these mutation types. Additionally, we explored whether internalizing problems increased with age, as would be consistent with findings in the general population. Methods. To test these hypotheses, internalizing problem scores (a parental report on the child behavior checklist) and intellectual ability (using different age- and range-appropriate intelligence and developmental tests) in a non-selected sample of children with TSC (N = 95, Age (Mean (SD) = 10.46 (4.25), 46.3% female, 28.5% TSC1) were assessed. To examine the association between internalizing problems and intellectual ability, several hierarchical regression analyses were performed. Externalizing problems, age, sex and the number of prescribed anti-epileptic drugs were included as control variables. For the exploratory hypothesis, this study tracked symptom severity over two follow-up visits in a subset of our patient population, using several paired sample t-tests. To additionally check whether internalizing problems became more severe in (early) adolescence we selected 15 children (66.7% female) for the childhood/adolescence subgroup. Within these groups, sex- and mutation related differences were also considered. Results. A significant model was found (F = 10.53, p <.001) in which externalizing problems (B = .55, p <.001) and age (B = .28, p <.005) were positively associated with internalizing problems. However, intelligence levels were found to have no influence. Furthermore, internalizing problems tend to increase with age (p <.001). Between childhood and adolescence, this increase was predominantly observed in girls (p = .03). Boys did not seem to experience more internalizing problems during this transition period. Lastly, a trend was found in which only a mutation on the TSC2 gene was associated with more internalizing problems over time (p <.005). Conclusion. This study could not confirm an association between internalizing problems and intelligence. However, our results indicated that internalizing problems increased with age, especially in girls. Since these behaviors contribute to the burden of the disease, it is of great importance that all involved professionals are sensitive to internalizing problems. A regular and thorough evaluation of internalizing problems should therefore always be part of the psychiatric assessment.Show less