Adult Outcome of Children With Attention-deficit/Hyperactivity Disorder
Condition: Attention Deficit Hyperactivity Disorder
MeSH terms: Hyperkinesis; Attention Deficit Disorder with Hyperactivity
Study type: Observational

Summary: 
      Attention deficit/hyperactivity disorder (ADHD) has been recognized as a common (5-8%),
      early-onset, long-term impairing, heterogeneous neuropsychiatric disorder with high
      heritability. Due to its lifelong impairments up to adulthood, adult ADHD has drawn much more
      attention in Western studies in the past decade; however, there has been no such study in
      Asian countries. The ultimate goals of this longitudinal follow-up study are to investigate
      the outcomes of a cohort of children with attention-deficit/hyperactivity (ADHD) and their
      healthy controls at young adulthood as the primary aim; and to test whether structural and
      functional brain connectivity can be endophenotypes of ADHD, to localize the brain area that
      are corresponding to methylphenidate treatment effects, and to identify the genetic variants
      corresponding to the persistence of ADHD, treatment effect of methylphenidate, neurocognitive
      dysfunction, and structural and functional dysconnectivity in the brain as the secondary
      aims. With the accomplishment of these goals, this study will provide the first-hand data on
      adult ADHD in non-western countries, and will be one of few world-class studies on the topics
      of neurocognitive and imaging genomics on adult ADHD.
    

Detailed description: 
      Primary specific aim:

      To describe the manifestation and persistence of ADHD symptoms and to investigate the
      psychiatric, social, and executive functioning outcomes at young adulthood among children
      with ADHD;

      Secondary specific aims

        1. To identify early individual (clinical, behavioral, and executive functioning and other
           neurocognitive variables), family, school, environmental factors to predict the symptom
           persistence and a wide-range of outcomes at young adulthood;

        2. To validate structural and functional connectivity of frontostriatal circuitry as
           imaging endophenotypes of ADHD by demonstrating that structural connectivity and
           functional connectivity of frontostriatal circuitry are altered in patients with ADHD
           and their unaffected siblings, are associated with ADHD symptoms, and are associated
           with genes related to dopamine neurotransmitter system;

        3. To identify brain area that is corresponding to the effect of methylphenidate; and

        4. To confirm reported candidate genes related to dopamine and noradrenergic
           neurotransmitter systems in the association with ADHD severity and subtypes
           (persistence, comorbidity, functional impairment, and treatment effects) and
           endophenotypes (executive function and structural and functional brain connectivity)
           such as DAT1, DRD4, MAO-A, ADRA2A, ADRA2C, NET, and COMT.

      The sample consists of a cohort of 217 young adults (180 males, 83%) who were diagnosed of
      ADHD at childhood and 173 healthy controls (123 males, 71%). At their ages of 17-24 (around 6
      years after their assessments at adolescence), they will receive psychiatric interviews
      (ADHD+SADS, CAADID) to make the diagnosis of ADHD and other psychiatric disorders and blood
      sample collection. They will complete the following questionnaires: ASRS and CAARS-S:S for
      adult ADHD symptoms, TPQ for personality characteristics, ASRI-4 for DSM-IV psychopathology,
      AAQoL and WFIRS for social functions, and PBI for parenting styles; and perform the WAIS-III
      for current IQ and Cambridge Neuropsychological Test Automated Batteries for attention
      control and executive functioning. Among the cohort subjects, 30 subjects with persistent
      ADHD and their same-sex and -handedness unaffected siblings (n = 30), 30 ADHD subjects who
      have DAT1 and/or good response to methylphenidate (repeated MRI assessment one week later)
      based on clinical assessment, and 30 subjects without lifetime ADHD and any psychiatric
      disorder will receive diffusion spectrum imaging (DSI) and resting state functional MRI
      assessments (total number of MRI assessments, 150). We will genotype 3'VNTR of DAT1 gene and
      other candidate genes involving dopaminergic and adrenergic systems (DRD4, MAO-A, ADRA2A,
      ADRA2C, NET, and COMT) for case-control association studies by using SNP and haplotype
      analysis.

      We anticipate that this study (1) will provide the first prospective, longitudinal data of
      children with ADHD at late adolescence and young adulthood in Asian populations; (2) will be
      one of the first to establish a comprehensive, multi-dimensional dataset combining clinical,
      family, psychosocial, academic/vocational, neuropsychological, neuroimaging, and genetic data
      of young adults with ADHD. With the inclusion of imaging genetics data, the behavioral and
      neurocognitive phenotypes of ADHD can be validated, the imaging endophenotype can be tested,
      and image genetics approach may help identify genetic variants for ADHD.
    

Observational model: Cohort
Time perspective: Other
Sampling method: Non-Probability Sample
Study population: 
        The sample will consist of (1) 217 adolescents (180 males, 83%) who were diagnosed of ADHD
        at childhood and followed up by Gau and consented to this follow-up study, and (2) 173
        healthy controls (123, Males, 71%) without lifetime ADHD to late adolescence and adulthood.
        This cohort was established from 2005 to 2008. We will invite them for complete assessments
        6 years after their assessments at adolescence according to the original assessment
        schedules from 2005-2008. The estimated age ranges are 17-24 years old.
      
Biospecimen description: 
      The subjects will receive blood withdrawal. The blood sample will be used for establishing
      lymphoblastoid cell lines, which will be used for molecular genetic experiments.