100 Chapter 3 Firstly, the role of genetic variation is evaluated. Several studies found single nucleotide polymorphisms (SNPs) in the MR and GR gene, which could contribute to inter-individual differences in increased glucocorticoid sensitivity and neurobehavioral and sleeping problems.7,9,12,15-20 Carrier status of specific relevant SNPs which have been linked before to psychopathology or sleeping problems may be associated to dexamethasone-induced side effects. Secondly, dexamethasone pharmacokinetics may play a role. Dexamethasone clearance is higher in younger children, hence taking an inter-patient variability in dexamethasone levels during maintenance phase into account is important.21 Thirdly, psychosocial and environmental factors may influence the severity of neurobehavioral side effects. It has been previously shown that the child’s distress during procedures in childhood cancer treatment is associated with parental distress.22 Parental stress is associated with behavioral problems in children.23 Overall, parental stress could potentially accelerate the development of dexamethasone-induced behavioral problems.24 Furthermore, some social (family) risk factors, but also psychosocial support can influence coping strategies of parents and may thereby influence their perceptions of the problems caused by dexamethasone.25,26
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