Cortical Excitability: Phenotype and Biomarker in Attention-deficit, Hyperactivity Disorder (ADHD) Therapy

The purpose of this study is to find out if children with attention-deficit, hyperactivity disorder (ADHD) have a difference in how their brain cells "fire" or react. The investigators also want to find if brain cell "firing" can tell us how severe of symptoms a child has from ADHD. Finally, the investigators want to see if giving an ADHD medication called atomoxetine can make the ADHD symptoms in a child better and if the improvement shows a change in brain "firing".

This study will evaluate Short Interval Intracortical Inhibition (SICI) measured by pTMS as a marker of the hyperactive-impulsive dimension in 120 ADHD 7-12 years, medication-free children. This study will characterize the effects of a single dose of atomoxetine compared to placebo on cognitive correlates of SICI change. Participants will be randomized 2:1 to either atomoxetine or placebo. The study will also characterize the effects of four weeks of atomoxetine treatment on cortical inhibition and will correlate SICI change with clinical outcomes.

Eligibility Criteria:
Inclusion Criteria:

1. Signed informed consent and assent
2. Meets DSM-IV criteria for ADHD, combined or inattentive subtype, based on K-SADS interview
3. Scores at least 1.5 SD higher than age and gender mean on ADHD RS, keyed to ADHD subtype (i.e., combined score for the combined subtype, inattentive subscale only for inattentive subtype, etc.)
4. Age: 7 - 12 years at study entry
5. Findings on physical exam, laboratory studies and ECG are judged to be normal for age and gender, as determined by study physician at study entry
6. There is not a co-existing medical condition for which TMS or ATX is contraindicated (for example pheochromocytoma).
7. Pulse and blood pressure within 95% of age and gender mean
8. Full scale IQ \>75 (i.e., excluding mental retardation and the lower level of the borderline range)
9. Able to complete study instruments and swallow capsules
10. Willing to commit to the entire visit schedule for the study
11. No previous treatment with Atomoxetine
12. Must either be naive to ADHD study medication or not doing well on the current ADHD medication.

Exclusion Criteria:

1. Has one of the following exclusionary diagnoses: autism/ pervasive developmental disorder, mental retardation, schizophrenia, a psychotic disorder, bipolar disorder, severe depressive or conduct disorder
2. Has a comorbid disorder that is otherwise allowable, but which requires a treatment that is not being offered in the study, and should be the primary focus of treatment, in the opinion of the PI
3. Has a medical or neurologic disorder that would preclude taking the ATX, or which would potentially confound the assessment of ADHD and/or TMS outcomes, in the opinion of the PI (for example pheochromocytoma, or for specific purposes of this study uncontrolled seizure disorder or organic brain syndrome).
4. Taking a systemic medication which might interfere with the metabolism or efficacy assessment of ATX in this study
5. History of allergic reactions to multiple medications
6. History of alcohol or drug abuse in the past 3 months Has been in a medication treatment study in the past 30 days
7. Females of childbearing age who are sexually active, do not use acceptable birth control (double barrier method), or are not abstinent. Abstinence is defined as no sexual activity for at least 3 months before the start of the study and the intention to abstain from sexual activity during the study period). Double barrier methods allowed include: condoms or diaphragms combined with spermicide use, intrauterine devices (IUD), and oral, transdermal, injectable or implantable hormonal medications (Ortho-Evra, Norplant, Depo-Provera, and similar prescription products) for at least one month before entering the study and continuing its use throughout the study. Birth control pills alone are not acceptable forms of birth control for this study.
8. Has any prior neurological condition that might increase the risk of an adverse event with TMS. For the purpose of this study we are excluding children with a current or prior history of epilepsy.