The Relationship Between CES1 Genotype and Methylphenidate Response in Children With ADHD - INDICES Work Package 6
Condition: ADHD
Study type: Observational

Summary: 
      This is a prospective observational study of a cohort of children diagnosed with Attention
      Deficit Hyperactive Disorder (ADHD) and followed with weekly assessments during the first 12
      weeks of Methylphenidate (MPH) treatment, and after three years.

      The overall aim is to gain knowledge in order to develop guidelines for more individualized
      treatments with (MPH), obtain a better drug response, and reduce the risk of adverse
      reactions, in order to improve adherence and long-term outcome.
    

Detailed description: 
      The study has three aims:

        1. Examine the effect of carboxylesterase 1 (CES1) genotype in children with ADHD on the
           effectiveness and adverse reactions of treatment with MPH.

        2. Study predictors for the short- and long-term outcome in childhood ADHD

        3. Examine the long-term outcome with respect to ADHD symptoms, and impairment in daily
           functioning in the cohort

      The specific aims are to:

        -  Describe the treatment response during the first 12 weeks after initiation of IR-MPH
           treatment, based on weekly clinician- rated ADHD core symptoms, the rate of
           normalisation/ borderline normalisation of ADHD core symptoms, adverse reactions, daily
           and social functioning, and measures of sustained attention.

        -  Describe the three-year outcome, based on parent rated ADHD core- and behavior symptoms,
           and level of impairment in daily functioning.

        -  Provide information about predictors for outcome after 12 weeks: clinical
           characteristics at entry (sex, age group, global severity of psychiatric disorder,
           psychiatric comorbidity, subtype of ADHD diagnoses), and predictors for outcome after
           three years: sex, age group, baseline severity of ADHD- and behavior symptoms, IQ,
           parental psychiatric disorder, maternal educational level, and time to treatment
           response.

        -  Determine the end-dose of IR-MPH after 12 weeks of treatment.

        -  Systematically sequence the CES1 gene and associate the identified genotypes of this
           gene with treatment responses, including dosage of IR-MPH
    

Intervention name(s): Methylphenidate
Intervention type(s): Drug
Intervention description(s): Treatment with methylphenidate through dose escalation
Other intervention name(s): Medikinet - N06BA04; Motiron - N06BA04
Intervention MeSH terms: Methylphenidate
Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        207 MPH naïve boys and girls aged 7-12 years with a recent ICD-10 diagnosis of hyperkinetic
        disorder (F90.0-90.9) or attention deficit disorder without hyperactivity (F98.8) and
        clinical indication for treatment with IR-MPH.

        Patients referred to the Child and Adolescent Mental Health Centre, Mental Health Services
        (Capital Region of Denmark) in the period from 1st of May 2012 to 1st August 2014, and who
        were suspected of having ADHD were consecutively screened for study eligibility.
      
Biospecimen description: 
      DNA from saliva collected in the Oragene OG-250 DNA kit (DNA Genotek Inc., ON, Canada).