Last updated on February 2018

Neuropsychology Neuroimage and Neurophysiology in Adults With ADHD

Brief description of study

We anticipate that drug-nave 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-nave 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 Study 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

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.

Clinical Study Identifier: NCT02642068

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Susan Shur-Fen Gau Gau, MD, ...

National Taiwan Univeristy Hospital
Taipei, Taiwan
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