Neuropsychology, Neuroimage and Neurophysiology in Adults With ADHD
Condition: Attention Deficit Hyperactivity Disorder
MeSH terms: Hyperkinesis; Attention Deficit Disorder with Hyperactivity
Study type: Observational

Summary: 
      We anticipate that drug-naïve ADHD probands, particularly those with DAT1 or SLC6A2 gene
      variants may have higher level of altered microstructural integrity of frontostriatal (FS),
      frontoparietal (FP), other hypothesized fiber tracts and decreased brain activity of FS, FP,
      and other circuits, deficits in ERP, and impaired EF, SA, IIA and VM than probands without
      DAT1 or SLC6A2 gene variants or adult neurotypical. The alterations in the structural and
      functional connectivity, neurophysiological and neuropsychological functioning would be
      observed in the unaffected siblings as compared to neurotypical. The unaffected siblings will
      be in the intermediate position between drug-naïve adult ADHD probands and neurotypical. The
      genetic dosage is anticipated to pose the strongest effects on the cortical thickness, brain
      volume, gyrification and microstructural property of white matter, followed by
      neurophysiology, functional connectivity, and neuropsychological function with the least
      effect.

      In terms of longitudinal follow-up part, we also anticipated despite increasing thinning of
      cortical thickness, microstructural integrity of several targets fiber tracts, and brain
      activity of target brain regions and improving performance in EF, SA, IIV, VM from childhood
      to late adolescence and young adulthood in the neurotypical group, the slopes of
      developmental trajectories of these neuroimaging and neuropsychological function are lower in
      the ADHD group.
    

Detailed description: 
      Attention deficit/hyperactivity disorder (ADHD) is a common (3-10%), early-onset, clinically
      and genetically heterogeneous neuropsychiatric disorder with lifelong neuropsychological
      deficits. Despite extensive research in adult ADHD in western countries, there has been no
      published data about adult ADHD in Taiwan except the PI's and colleagues' previous works on
      pharmacotherapy in adults with ADHD and only few endophenotype studies based on adults with
      ADHD in the world. The ultimate goals of this 5-year project are to identify which
      neuropsychological, functional and structural connectivity, and neurophysiological variables
      can be effective endophenotypes (biomarkers) for ADHD based on unaffected sibling (1st-3rd
      years) and follow-up (4th-5th years) designs. With the accomplishment of the following study
      goals, this study will be the first study on the topics of neuroimaging and
      neurophysiological endophenotypes on adult ADHD using advanced imaging techniques (i.e.,
      Tract-based autonomic analysis, TBAA) and comprehensive clinical and neurocognitive data.
      This proposal has one primary aim and four secondary aims:

      Primary Aim:

        1. To validate structural (assessed by TBAA using diffusing spectrum imaging, DSI) and
           functional connectivity (assessed by resting-state fMRI) in frontostriatal,
           frontoparietal and other circuitries, and neurophysiological functions (assessed by
           stop-signal event-related potential [ERP]: N2, P3, ERN, Pe) as effective imaging
           endophenotypes by demonstrating the intermediate position of unaffected siblings between
           ADHD probands, and age-, sex-, handedness-, and IQ-matched adult neurotypical and
           association with DAT1 and NET (SLC6A2) variants;

           Secondary Aims:

        2. To validate the executive functions (EF), sustained attention (SA), intraindividual
           variability (IIV), visual-spatial memory (VM) as effective neurocognitive endophenotypes
           by demonstrating the intermediate position of unaffected siblings between ADHD probands,
           and adult neurotypical;

        3. To examine the developmental trajectory and stability of neuropsychological functions
           and structural and functional connectivity from childhood to adolescence and young
           adulthood;

        4. To correlate the data from structural (morphometric, cortical thickness, gyrification,
           fiber tract integrity) and functional connectivity (rsfMRI), neuropsychology (Executive
           function, visual-spatial memory, sustained attention, variability), neurophysiology
           (Stop-signal ERP) and ADHD core symptoms stratifying by the presence of ADHD, presence
           of DAT1 and NET (SLC6A2) variants, proband-unaffected sibling dyads, and different
           developmental stages.
    

Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        This 5-year proposal consists of two parts: (1) a 3-year case-control study with unaffected
        siblings and adult neurotypicals as controls to investigate the brain structural
        connectivity, functional connectivity, neurophysiological, neuropsychological functioning
        in 60 probands with ADHD, their unaffected siblings (at least 30 same-sex siblings,
        n=30~60) and age-, sex-, handedness-, and IQ-matched neurotypicals (n=90~120) with
        estimated total sample size as at least 180 up to 240. (2) a 2-year follow-up study to
        repeat the neuropsychological and MRI assessments and to assess electrophysiology related
        to inhibition controls of 40 adolescents and young adults with childhood diagnosis of ADHD
        and 40 neurotypicals who had same neuropsychological and imaging assessments in
        2010.8-1013.7.
      
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
    
Keywords: Drug-naïve Adult ADHD; Neuropsychology; Neurophysiology; Neuroimaging; Follow-up