The aim of this study is to examine the mechanisms by which stimulant medications reduce symptoms in patients with Attention Deficit Hyperactivity Disorder (ADHD). Using Magnetic Resonance Imaging (MRI), the investigators have found that the volumes of certain brain regions are reduced in patients with ADHD. The reduced volumes were much less pronounced if patients had been treated with stimulant medications, suggesting that stimulants may reduce the symptoms of ADHD by reversing these volume reductions. In a second and related study, the investigators found that in patients with ADHD, emotional processing was normalized when patients were taking stimulant medications. Both studies point to possible mechanisms by which stimulants are effective; however, a significant limitation of these findings is that they were derived from cross-sectional studies.

In this current study, the investigators hope to replicate these treatment effects of stimulants in a prospective, controlled manner. The investigators plan to measure ADHD symptom severity in patients before and after 12-weeks of controlled treatment with either a stimulant medication or placebo while utilizing structural and functional MRI. Combining imaging with a randomized controlled trial will allow us to better assess the effects of stimulants on brain function and structure.

A cohort of 100 patients with ADHD will be recruited for a 12 week, double-blind, parallel, randomized controlled trial of Lisdexamfetamine (Vyvanse) versus placebo, with 50 patients randomized to Lisdexamfetamine and the other 50 patients to placebo. The investigators will acquire high-resolution, anatomical and functional MRI images at baseline and after 12 weeks of treatment.

In addition, 75 age- and sex-matched healthy control subjects will be imaged at baseline.

Inclusion Criteria:

ADHD Participants: Meets Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) criteria for a primary diagnosis of ADHD, any subtype.

Healthy Control Participants: No current DSM-IV-TR Axis I psychiatric diagnosis.

All Participants:

1. Male or female, 6 - 25 years of age, and in good physical health
2. English-speaking

Exclusion Criteria:

1. Current comorbid DSM-IV-TR Axis I psychiatric diagnosis or other symptomatic manifestations that, in the opinion of the examining physician, will contraindicate Lisdexamfetamine treatment or confound safety assessments
2. Meets DSM-IV-TR criteria for active substance abuse and/or dependence
3. Lifetime history of cocaine or stimulant abuse or dependence
4. Actively suicidal
5. Children and adolescents: Prior treatment with psychostimulants for longer than 1 month duration and/or treatment with psychostimulants within the past 4 months Adults: Treatment with psychostimulants within the past 12 months.
6. Documented allergy or intolerance to Lisdexamfetamine or other stimulant medications.
7. Taking other medications with central nervous system effects.
8. History of seizure (other than febrile seizure)
9. Diagnosis of hyperthyroidism, glaucoma, or other serious medical illness.
10. Personal or family history of medical conditions, such as cardiovascular disease, that may interfere with study participation, or for which treatment with Lisdexamfetamine may pose a risk
11. Pregnant or lactating
12. MRI contraindications such as pacemaker, braces, etc.
13. Full scale intelligence quotient (FSIQ) less than 70

Analysis population includes participants who completed the study.

Adverse event data were collected through study completion, an average of 12 weeks.

Adverse events were routinely collected from ADHD participants receiving treatment using the Pittsburgh Side Effects Rating Scale. A physician met with participants in person approximately once per week during treatment. The physician was also available by phone between visits.