A Longitudinal Follow-up Study of Neuroimage and Neuropsychological Endophenotype Study on ADHD
Condition: Attention Deficit Hyperactivity Disorder
MeSH terms: Attention Deficit Disorder with Hyperactivity
Study type: Observational

Summary: 
      Attention deficit/hyperactivity disorder (ADHD) is a common (3-10%), early-onset, clinically
      and genetically heterogeneous neuropsychiatric disorder with lifelong neuropsychological
      deficits. Despite many imaging studies on ADHD across countries, only few longitudinal
      studies investigated the developmental changes of structural and functional brain
      connectivity and some imaging studies using unaffected sibling design in western countries.
      There is no published data regarding developmental changes in brain functions assessed by
      neuropsychology/physiology/image in Asia and Taiwan as well. The ultimate goals of this
      3-year project are to identify which neuropsychological, functional and structural
      connectivity, and neurophysiological variables can be effective endophenotypes (biomarkers)
      for ADHD based on this follow-up unaffected sibling study design. Due to the limitation of
      diffusion tensor image (DTI), original analysis of diffusion spectrum image (DSI), and
      single-echo resting-state functional MRI (SE rsfMRI), the investigators will adopt Mean
      Apparent Propagator (MAP)-MRI, tract-based autonomic analysis (TBAA) and multi-echo (ME)
      rsfMRI in this project. With the accomplishment of the following study goals, this study will
      be the first longitudinal follow-up neuroimaging/physiological endophenotypes study on ADHD
      using advanced imaging techniques and comprehensive clinical and neurocognitive data.
    

Detailed description: 
      Primary Aim:

        1. To examine the developmental changes and stability of neuropsychological functions (NFs,
           assessed by CPT and CANTAB) and structural (morphometric, cortical thickness,
           gyrification, fiber tract integrity) and functional connectivity (assessed by SE rsfMRI,
           counting-Stroop fMRI) from childhood to late adolescence and young adulthood;

           Secondary Aims:

        2. To validate a wide range of neuropsychological functions (assessed by CPT, CANTAB, CNB),
           structural and functional connectivity in the frontostriatal (FS), frontoparietal (FP)
           and other circuitries, and neurophysiological functions (assessed by event-related
           potential [ERP]: MMN, Gamma ARRS) as effective imaging endophenotypes by demonstrating
           the intermediate position of unaffected siblings between ADHD probands, and age-, sex-,
           and handedness-matched neurotypicals at Time 1 and Follow-up;

        3. To identify the Time 1 predictors (behavioral symptoms, NFs, and imaging data) for
           Follow-up neuroimaging data (Morphometric, DSI, rfMRI, task-fMRI, MMN, Gamma ARRS); and

        4. To correlate all kinds of neurocognitive data and clinical symptoms profiles stratifying
           by the presence of ADHD, proband-unaffected sibling dyads, and two time points.

      Hypothesis The investigators anticipated despite increasing thinning of cortical thickness,
      microstructural integrity of several targets fiber tracts, and brain activity of target brain
      regions and improving neuropsychiatric performance from childhood to late adolescence/young
      adulthood in neurotypicals and probably in ADHD with lower developmental changes slope in
      ADHD. These changes of unaffected siblings are in the intermediate position between the ADHD
      probands and neurotypicals. For the endophenotype part, the investigators anticipate that
      ADHD probands may have a higher level of altered microstructural integrity and decreased
      brain activity of the FS, FP, other hypothesized fiber tracts/brain networks, deficits in MMN
      and Gamma, and impaired a wide-ranging NFs than neurotypicals. These differences in the
      unaffected siblings would be in the intermediate position between ADHD probands and
      neurotypicals.
    

Intervention name(s): Psychiatric diagnosis
Intervention type(s): Other
Intervention description(s): Kiddie Schedule for Affective Disorders & Schizophrenia (K-SADS) for DSM-5
Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        This 3-year follow-up study will repeat the same neuropsychological (CANTAB, CPT) and MRI
        (T1, T2, DSI, SE- rsfMRI, counting stroop fMRI) assessments at Time 1 and additionally
        assess electrophysiology (MMN, Gamma ASSR), fMRI (ME rsfMRI, tasks fMRI) and Computerized
        Neuropsychological Battery (CNB) among 138 probands with ADHD, 61 unaffected siblings, and
        135 neurotypicals who had the same neuropsychological and imaging assessments in
        2010.8-2015.7(NCT00916851, NCT01682915).