Attention-deficit hyperactivity disorder (ASD) is a highly heritable impairing neurodevelopmental disorder with deficits in a wide range of executive functions, yet the search for definite genetic etiologies remains elusive. The advance in neuroimage methodology has markedly improved our understanding of brain structure and function of ADHD in the past decade. With the support by MOST and NHRI, we have collected a comprehensive set of clinical, neuropsychological, image (T1, T2, diffusion spectrum image [DSI], resting-state functional MRI, counting-Stroop fMRI), and DNA of ADHD probands and their unaffected siblings. This lecture on ADHD image studies focuses on three parts: image endophenotype, image genomics, and pharmacotherapy effects.
　　First, delineating ADHD endophenotypes can help to identify its genetic etiologies and pathophysiology. Our previous work has found that some executive functions (e.g., working memory, planning, set-shifting), visual memory, information processing, intra-individual variability of reaction time can be potential neurocognitive endophenotypes. We further found less activation in the left superior parietal lobule, and abnormal AD values of specific white matter tracts might be considered as a candidate imaging endophenotype in ADHD; however, increased functional segregation related to the salience network and lower RD values in the right frontostriatal tract connecting ventrolateral prefrontal cortex may be the features against developing ADHD.
　　Second, our results showed the DAT1-related grey matter volume alterations in the posterior cortical regions contributing to visual memory performance in children with ADHD. We further identified two novel gene-brain-behavior associations between the left dorsal caudate functional connectivity and visual memory performance in ADHD youths with the DAT1 rs27048 (C)/rs429699(T) haplotype, and between the intrinsic brain activity of the sensorimotor and dorsal attention networks with  visual memory and visual attention in ADHD children with the SLC6A2 rs36011 (T)/rs1566652 (G)haplotype.
　　Third, despite extensive research on the efficacy of methylphenidate and atomoxetine on reducing ADHD core symptoms, social function, and life quality, there was relatively much fewer data on neuropsychological and imaging measures. Our previous clinical trials are showing differential efficacy of methylphenidate and atomoxetine on a wide range of neuropsychological functions in youths and adults, suggesting different cognitive mechanisms. We conducted 8-week atomoxetine; placebo-controlled double-blind, randomized clinical trial among 24 drug-naïve adults with ADHD, and 12-week atomoxetine versus methylphenidat head to head randomized clinical trial among 50 drug-naïve children with ADHD. Our rsfMRI and counting-Stroop fMRI analyses demonstrated significantly differential effects of these two medications on functional brain changes and no effect from brain function if treatment with placebo.
　　In conclusion, the latest results from NTUH regarding image endophenotype, imagenomics, and treatment effects of two commonly used medications will be presented.