Brain Changes in Children and Adolescents With Behavioral Problems

Condition(s) targeted: Attention Deficit Disorder With Hyperactivity; Mental Disorders Diagnosed in Childhood

Phase: N/A

Status: Recruiting

Sponsored by: National Institute of Mental Health (NIMH)

Overall contact:
Patient Recruitment and Public Liaison Office, Phone: (800) 411-1222, Email: prpl@mail.cc.nih.gov

This study will examine brain changes in children and adolescents with behavioral problems and compare them to children and adolescents without behavioral problems.

Children between 8 and 17 years of age with attention deficit hyperactivity disorder (ADHD) or anti-social behavior or who are healthy normal volunteers may be eligible for this study. Candidates are screened with a medical history and physical examination, mental health and psychiatric interviews, blood test, and urine drug screen. Children who are taking atomoxetine (Stattera), bupropion (Wellbutrin), modafinil (Provigil), or similar medications for behavioral problems are excluded.

Participants have the following procedures over two separate visits:

- Visits 1 & 2, Standardized testing: Children undergo standardized tests designed to

measure language, math, memory abilities, and intelligence. Children with ADHD or behavior problems must not take any medications for their disorder, such as stimulants related to amphetamine or methylphenidate for 48 hours before testing, and no over-the-counter medications for 5 days before testing. Healthy control participants must not take any prescription or over-the-counter medicines for 5 days before testing. In addition to testing, participants learn how magnetic resonance imaging (MRI) scans are performed in preparation for the next visit. A urine sample is collected for a drug screen.

- Visit 3, MRI scan: MRI uses strong magnetic fields and radio waves to measure changes in

brain tissues. During the procedure, the child lies on a table in a space encircled by a metal cylinder (the MRI scanner) for 60 to 90 minutes and must lie still for 10 to 15 minutes at a time. While in the scanner, the child is asked to perform some tasks on the computer involving responding to pictures or making simple decisions. Children with ADHD or behavior problems must not take any medications for their disorder, such as stimulants related to amphetamine or methylphenidate, for 48 hours before scanning, and no over-the-counter medications for 5 days before MRI scanning. Healthy control participants must not take any prescription or over-the-counter medicines for 5 days before the scan. A urine sample is collected for a drug screen before the test. Female participants are tested for pregnancy before the scan and are not scanned if the pregnancy test is positive.

Participants may be invited to participate in a genetics study and a study of fatty acids in the blood.

Official title: Investigating the Neuro-Cognitive Underpinnings of the Emotional Dysfunction Linked to Childhood Behavioral Disturbance

Study design: N/A

Detailed description: OBJECTIVE:

The goal of this protocol is to investigate the neuro-cognitive underpinnings of the emotional dysfunction linked to childhood behavioral disturbance; in particular, psychopathic tendencies but also ADHD. The functional hypotheses that we are testing with both neuro-cognitive and neuro-imaging paradigms are that: (1) psychopathic tendencies, but not ADHD, are associated with dysfunction in the formation and operational use of stimulus-punishment and, to a lesser extent, stimulus-reward association information; and (2) that ADHD, but not psychopathic tendencies, is associated with impairment in executive systems related to the representation and execution of task demands.

STUDY POPULATION:

160 Children with psychopathic tendencies; 160 children with ADHD; and 160 healthy volunteer children. All Children will be between the ages of 10 and 17. Both males and females will be enrolled.

DESIGN:

The current study will have three phases: i) participant screening (up to 3 hours); ii) neuropsychological assessment and training in an MRI simulator (up to 4 hours); iii) The MRI scanning session (up to 2 hours, no more than 90 minutes in scanner). Participants, if they are willing, may be invited to participate in more than one scanning session (up to a maximum of 3 120 minute sessions) or neurocognitive testing session.

OUTCOME MEASURES:

Behaviorally, we predict that children with psychopathic tendencies will present with impairment on tasks that involve either the formation or operational use of particular stimulus-punishment associations (e. g., the subjective value learning task and emotional interrupt task). In contrast, we predict that children with ADHD, but no indications of psychopathic tendencies, will show no behavioral impairment on such tasks. However, we predict that children with ADHD will present with impairments on executive function tasks (e. g., the Number Stroop paradigm). In contrast, we predict that children with psychopathic tendencies will show no impairment on these tasks. At the anatomical level, we anticipate reduced activation of emotional related systems in children with psychopathic tendencies during response selection and emotional impact tasks (in particular, reduced activation of the amygdala, regions of orbitofrontal cortex and anterior cingulate). We anticipate that the neural response of children with ADHD during these tasks will be less anomalous. We anticipate that the neural response of children with ADHD during the performance of response control tasks to be anomalous (with considerable greater recruitment of anterior and posterior compensatory systems).

Minimum age: 8 Years. Maximum age: 17 Years. Gender(s): Both.

Criteria:

- INCLUSION CRITERIA:

1. Individuals with psychopathic tendencies: Male and female subjects aged 8-17 who score equal to or more than 20 on the APSD/PCL-YV.

Children with antisocial behavioral problems on medications with psychotropic effects will be considered if their target behaviors persist despite the use of medications. In these children, only simple stimulant medications will be held for 48 hours. These include methylphenidate, amphetamine and their derivatives including Ritalin, Ritalin SR, Ritalin LA, Methylin, Methlin ER, Metadate CD, Concerta, Dexedrine, Dextrostat, Dexedrine Spansule, Adderall, Adderall XR, and Focalin. Medications like Strattera (atomoxetine), bupropion (Wellbutrin), modafinil (Provigil), or valproic acid (Depakote), or other mood stabilizers are not safe to stop suddenly and children taking these medications will not be asked to stop them.

2. Individuals with ADHD: Male and female subjects aged 8-17 who currently meet DSM-IV criteria for ADHD. The diagnosis will be made on the basis of a K-SADS-PL [50] interview with the parent and a t score greater than 65 on the hyperactivity-impulsivity subscale of the Connors Teacher Scale. Participants in this group will have APSD scores less than 20.

3. Comparison individuals: Male and female subjects aged 8-17 who are free from any current or past psychopathology (all will score less than 20 on the APSD/PCL-YV).

4. Children with antisocial behavioral problems on medications with psychotropic effects will be considered if their target behaviors persist despite the use of medications. In these children, only simple stimulant medications will be held for 48 hours. These included methylphenidate, amphetamine and their derivatives including Ritalin, Ritalin SR, Ritalin LA, Methylin, Methlin ER, Metadate CD, Concerta, Dexedrine, Dextrostat, Dexedrine Spansule, Adderall, Adderall XR, and Focalin. Medications like Strattera (atomoxetine), bupropion (Wellbutrin), modafinil (Provigil), or valproic acid (Depakote), or other mood stabilizers are not safe to stop suddenly and children taking these medications will not be asked to stop them.

EXCLUSION CRITERIA:

1. I. Q. less than 80.

2. Ongoing medical illness other than those listed in the inclusion criteria for the respective groups that requires use of any medication that may have psychotropic effects. For example, a patient with history of mild asthma that did not require medication may be included, however a patient with asthma requiring use of beta blockers, steroids, etc. would not be included. For children with ADHD or healthy volunteer children, a contraindication to discontinuing medication for 48 hours. Only simple stimulant medications will be held for 48 hours. These include methylphenidate, amphetamine and their derivative including Ritalin, Ritalin SR, Ritalin LA, Methylin, Methlin ER, Metadate CD, Concerta, Dexedrine, Dextrostat, Dexedrine Spansule, Adderall, Adderall XR, and Focalin. Medications like Strattera (atomoxetine), bupropion (Wellbutrin), or modafinil (Provigil) are not safe to stop suddenly and children with ADHD taking these medications will not be included.

3. Subjects with psychopathic tendencies who receive a diagnosis of an anxiety or mood disorder as determined by a clinical and K-SAD review conducted by a psychiatrist will be excluded. Additionally, children with active psychosis, pervasive developmental disorders or Tourette's syndrome will be excluded.

4. Individuals with ADHD will be be evaluated through the KSAD and clinical review by a psychiatrist. Those children who receive diagnosis of mood disorders through this evaluation process will be excluded. Additional explicit exclusions include active psychosis, Pervasive Developmental Disorders and Tourette's syndrome. Children with anxiety disorders will be included given the high comorbidity of ADHD and anxiety disorders.

5. Any other psychiatric disorder that is sufficiently severe to require specific treatment, with the exception of those listed in the inclusion criteria for the respective groups.

6. Neurologic disorder (including seizures).

7. Any metallic objects in the body. Metal plates, certain types of dental braces, cardiac pacemakers, etc., that are sensitive to electromagnetic fields contraindicate MRI scans.

8. Claustrophobia: participants will be questioned about potential discomfort in being in an enclosed space, such as an MRI scanner.

Patient Recruitment and Public Liaison Office, Phone: (800) 411-1222, Email: prpl@mail.cc.nih.gov

National Institutes of Health Clinical Center, 9000 Rockville Pike, Bethesda, Maryland 20892, United States; Recruiting

NIH Clinical Center Detailed Web Page

Related publications:

Ambrogi Lorenzini CG, Baldi E, Bucherelli C, Sacchetti B, Tassoni G. Neural topography and chronology of memory consolidation: a review of functional inactivation findings. Neurobiol Learn Mem. 1999 Jan;71(1):1-18. Review.

Aron AR, Fletcher PC, Bullmore ET, Sahakian BJ, Robbins TW. Stop-signal inhibition disrupted by damage to right inferior frontal gyrus in humans. Nat Neurosci. 2003 Feb;6(2):115-6. No abstract available. Erratum in: Nat Neurosci. 2003 Dec;6(12):1329.

Babinski LM, Hartsough CS, Lambert NM. Childhood conduct problems, hyperactivity-impulsivity, and inattention as predictors of adult criminal activity. J Child Psychol Psychiatry. 1999 Mar;40(3):347-55.

Starting date: February 2005
Last updated: July 18, 2008