Investigating the Impact of Methylphenidate on Neural Response in Disruptive Behavioral Disorder

Investigating the Impact of Methylphenidate on Neural Response in Disruptive Behavioral Disorder

Background:

- Disruptive behavior is a common problem for children and adolescents. It can be treated with some success with stimulant medicine. Researchers want to learn more about how this works.

Objective:

- To learn how the brain changes when taking the medicine methylphenidate for behavior problems.

Eligibility:

• Children ages 10 17 with conduct disorder and/or attention deficit disorder.
• Healthy volunteers the same age.

Design:

• Participants will be screened under a separate protocol.
• Participants will have two 3-hour sessions at the clinic. Girls who are menstruating will have a pregnancy test before their scans.
• Visit 1: All participants will:
• Perform simple tests on a computer.
• Fill out a questionnaire along with their parent or guardian.
• Have an MRI scan. A magnetic field and radio waves take pictures of the brain. Participants will lie on a table that slides into a metal cylinder. A coil will be placed over their head. They will be in the scanner for 60 minutes, lying still or performing a simple task. They will practice the task before the scan. A computer screen will show them task information during the scan. The scanner makes loud knocking sounds. Participants will get earplugs. Their parent or guardian can stay with them during the scan.
• Only participants with behavior disorders will:
• Take a pill of the study medicine or placebo.
• Be monitored for any side effects.
• Visit 2 is a repeat of Visit 1, except participants who got a pill in Visit 1 will get the other pill in Visit 2. For healthy volunteers, the 2 visits are exactly the same.

OBJECTIVE:

To determine the impact, as indexed by BOLD response, of the administration of dopaminergic agonist (methylphenidate) on the pathophysiology of CD/ODD.

STUDY POPULATION:

Youth with CD/ODD and typically developing (TD) youth.

DESIGN:

The study will involve a 2 session design (methylphenidate [MPH] vs. placebo). Patients with CD/ODD will participate in both sessions. TD youth will be tested for 2 sessions (no medication) to provide an index of typical task response. Activity within regions of interest identified from the TD youth will be used to determine whether MPH reduces differences in BOLD response in CD/ODD relative to TD youth. ICU scores and current ADHD symptomatology will be used as covariates to determine whether these variables moderate the putative increase in BOLD response in target regions in the patients with CD.

OUTCOME MEASURES:

Principle dependent measures will be BOLD responses as measured through core tasks.

• INCLUSION CRITERIA

Youth with CD

1. 10-17 years of age.

2. A current diagnosis of CD as determined by the Kiddie-SADS, lifetime version.

   • Youth in the CD+comorbid ADHD group will also meet diagnostic criteria for ADHD.
   • Youth in the CD without comorbid ADHD group will specifically not meet diagnostic criteria for ADHD.

3. Youth with CD shouldmust be na(SqrRoot) ve to psychoactive medication (such as: methylphenidate and amphetamine).

TD youth

1. 10-17 years of age.
2. No current psychiatric diagnosis, as determined by the Kiddie-SADS, lifetime version.

EXCLUSION CRITERIA

Exclusion criteria for youth with CD (with or without ADHD)

1. Comorbid psychotic, major mood, tic, pervasive developmental, and substance abuse disorders.
2. Presence of comorbid ADHD is exclusory for the group of patients with CD without ADHD
3. History of known structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems
4. Current weight less than 25kg or over 90kg

Exclusion criteria for all participants (CD with ADHD, CD without ADHD and TD)

1. History of serious CNS disease disorder (examples aresuch as: history of seizure, epilepsy, brain tumor, brain hemorrhage, and major CNS infection such as meningitis or encephalitis)
2. Previous history of known structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems
3. Current use of any psychiatric medications and centrally acting medications (such as stimulants, non-stimulant ADHD medications, antidepressants, anxiolytics, antipsychotics and anti-epilepsy medications), and past history of use of psychoactive medication (such as methylphenidate and amphetamine)
4. A positive urine pregnancy test
5. A Positive urine toxicology, History/current diagnosis of substance abuse/dependence
6. Suicidal or homicidal ideation within the past 6 months.
7. Wechsler Abbreviated Scale of Intelligence (WASI) (D. Wechsler, 1999) scores <70
8. Metal in body (i.e., hearing aid, cardiac pacemaker, bone plates, etc), claustrophobia, or any other condition that would preclude fMRI scanning.