138 Chapter 4 questions concerning perceived support, lack of understanding, and parental chronic illness. The internal validity of the DT-P ranged from 0.55 (social domain) to 0.91 (total score). Support and parental coping This unvalidated short questionnaire contained nine questions, divided in three sections. The first part was about whether a child and/or parent received psychological or other (medical) support and why (e.g. Has your child received help support from a psychologist in the past month?). The second part was about information the parent had received or looked up about dexamethasone (e.g. Have you ever received information about the possible side effects of dexamethasone in the areas of (multiple answers possible): weight, sleep, behavior, eating, bone problems, risk of infections, other). In the last part, parents were asked to describe how they usually cope with the dexamethasone treatment period (e.g. How do you prepare for the days when your child is on dexamethasone?). After five days of dexamethasone one question regarding support during this period was asked (Have you sought extra help for yourself or your child in the past 5 days?) Dexamethasone pharmacokinetics Blood plasma samples were stored at -80°C. Dexamethasone levels were assessed in EDTAplasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Precision of the assay was ensured by using quality control samples in each batch of samples. Between-run precision was 2.4%. The lower limit of the measuring interval (LLMI) was 1.0 nmol/L. Levels below the lower limit of the measuring interval (LLMI) were set to one half LLMI for the purpose of analyses. Candidate SNP assessment Wholeblood was stored at -80°C and shipped on dry ice. DNA was extracted using the ReliaPrep chemistry (Promega) on a Tecan robot. All samples were simultaneously genotyped with the GSA-MD (Multi-disease Finemapping) array version 3. Standard quality control was performed using Plink and zCall.57,58 Imputations were performed to the 1000 Genomes Phase 3v5 reference panel59 using SHAPEIT60 and Minimac461. We used a candidate single nucleotide polymorphism (SNP) approach. In adults, homozygous carriers of the Bcl-1 polymorphism have an increased risk for major depression.17 This was also found in a small (n = 49) sample of pediatric ALL patients.18 In another cohort of pediatric ALL patients, the rs4918 polymorphism (Alpha2-HS glycoprotein (AHSG) gene) was associated with impaired sleep during dexamethasone treatment. We therefore evaluated Bcl1 (rs41423247) and rs4918 (AHSG gene) polymorphisms as possible determinants for dexamethasone-induced neurobehavioral or sleep problems respectively. Imputation quality was 0.94 for the Bcl1 (rs41423247) SNP and 0.98 for the rs4918 SNP.
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