This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.OBJECTIVE: The primary objective will be to that relative to placebo, atomoxetine treated subjects with Attention Deficit Hyperactivity Disroder will show a greater increase in oxygen brain perfusion in the right orbitofrontal lobe and anterior cingulate as they perform tasks involving inhibitory control [as measured by event related functional magnetic resonance imaging (fMRI)]. The secondary objective will be to show that above changes in brain activation will correlate with the degree of clinical improvement as measured by teacher and parent rating scales.STUDY SUBJECTS: The child must meets DISC-P criteria for ADHD-combined, that is, he/she has 6 of the 9 criteria in both the Inattention and Hyperactivity/Impulsivity domains. The subjects academic performance on the Woodcock Johnson is within 1 SD of the mean of his/her full scale IQ and the full scale IQ must be at least 95. The neuropsychological testing should not show any deficit in phonological awareness/processing. The child must be above 1.5 SD of the mean for his/her age and sex on both the Cognitive Problems/Inattention and Hyperactivity factors of both the CTRS-R and CPRS-R. TREATMENT: Subjects will be randomized to receive placebo or atomoxetine for 2 weeks. Recently Michelson et al. (Michelson et al., 2002) showed that once daily atomoxetine was effective in the treatment of ADHD, furthermore robust differences from placebo were observed by weeks 1-2. Subjects in the atomoxetine arm weighing less than 70 kg will started on 0.5 mg/kg/day for 1-3 days, 0.75 mg/kg/day on day 4-5 and 1.2 mg/kg/day on days 6-7. Weight, vital signs and assessment for adverse events will occur on day 7. If the medication is well tolerated, the subject will remain on the 1.2 mg/kg/day for all of week 2. Conners parent and teacher rating scales will be obtained at the end of weeks 1 and 2. At the visit on day 14, the psychiatrist will review the rating scales, interview the parent and child, and obtain the Clinical Global Impression (CGI). A CGI score of 1 (Very Much Improved) or 2 (Much Improved) shall be required to define a child as a responder. A Student T-Test will be used to constrast the mean CGI scores in the atomoxetine and placebo groups. The CTRS and CPRS will be subjected to an ANCOVA comparing the week 2 placebo and atomoxetine scores using the baseline variable as a covariate. The FMRI scan will be scheduled within 3 days of the day 14 visit while the subject remains on the final dose of study medication.EVENT-RELATED fMRI: Children will undergo ER-fMRI during the Stop Signal Task and the Stroop Task to precisely localize activation areas. Inter-trial interval will be 2.0 sec for both tasks. For the Stop Signal Task, GO stimuli will consist of the letters A and B which will appear at the center of the screen for 150 msec. The child presses one button for the letter 'A', and a second button for the letter 'B'. On 25% of the trials, the GO stimulus will be followed by the STOP signal (a red triangle).
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