PET Scanning of Adults With Attention Deficit Hyperactivity Disorder (ADHD)
Condition: Volunteer; Attention Deficit Hyperactivity Disorder
MeSH terms: Hyperkinesis; Attention Deficit Disorder with Hyperactivity
Study type: Observational

Summary: 
      This study will explore the brain in men with and without attention deficit hyperactivity
      disorder (ADHD). It will use positron emission tomography (PET) and magnetic resonance
      imaging (MRI) to study brain function and nerve cell communication involving phospholipids
      (fatty molecules that make up the covering of nerve cell fibers in the brain and are involved
      in communication between the cells). It will also look at how nerve cell communication is
      related to blood flow. In particular, the study will explore communication through the
      dopamine system, which is one of the main neurotransmitter systems in the brain involved in
      ADHD.

      Healthy men and men with ADHD between 18 and 55 years of age may be eligible for this study.

      Participants undergo the following procedures:

      "<TAB>Medical history and psychiatric and medical evaluation, including blood and urine
      tests.

      "<TAB>MRI scan. This test uses a strong magnetic field and radio waves to obtain images of
      the brain. The subject lies still on a table that slides into the scanner (a metal cylinder)
      during the scanning.

      "<TAB>PET scanning. The subject lies on the scanner bed with his head held still using a
      special facemask. A catheter (plastic tube or needle) is placed in an artery to collect blood
      samples and in a vein to inject radioactive isotopes for measuring blood flow and
      phospholipid metabolism. Scans are done after an injection of a saline solution and again
      after injection of apomorphine, a medication that turns on dopamine receptors in the brain.
      The injections are given under the skin of the abdomen, about one and a half hours apart....
    

Detailed description: 
      A. Objective

      Attention deficit hyperactivity disorder (ADHD) is a heritable neurodevelopmental disorder
      with a reported male predominance that persists into adulthood and leads to significant
      morbidity in affected individuals. ADHD is currently hypothesized to reflect central
      dopaminergic dysfunction. Evaluation of human dopaminergic dysfunction using in vivo
      neuroimaging has been limited to studies of receptor localization and quantification, and
      dopamine synthesis, rather than direct measurement of the functional status of receptor
      signaling. There exists a need to thoroughly elucidate mechanisms underlying aberrant
      dopaminergic neurotransmission downstream of receptor activation in signaling processes. We
      have developed an in vivo method to measure neuroreceptor-initiated signal transduction
      involving activation of phospholipase A(2) to release the second messenger, arachidonic acid
      (AA). We propose to use positron emission tomography (PET) to quantitatively image
      dopamine-initiated signal transduction via AA in ADHD patients and healthy volunteers, in
      subjects administered the dopaminergic agonist, apomorphine, and to measure regional cerebral
      blood flow (rCBF) as well. We hypothesize that signaling and flow responses to apomorphine
      will be elevated, demonstrating hypersensitivity of the dopamine signaling mechanism.

      B. Study population

      18 healthy male volunteers between the ages of 18 and 55, will be recruited for this study
      (see justification for recruitment of males only in Study Design and Methods).

      C. Design

      All subjects will have up to four study-related visits to the Clinical Center in Bethesda
      over a one-year period, including an overnight stay. Participants will also be asked to
      complete an initial comprehensive telephone questionnaire to elicit whether they meet
      criteria for study participation, followed by on-site visits to NIH to complete a modified
      battery of neuropsychiatric screening tests related to symptom presence and severity.
      Questions relating to medical, family, psychiatric and developmental histories and lifestyle
      will be asked. In addition, visits will include a physical exam as well as blood and urine
      collection, and structural magnetic resonance imaging (MRI) of the head. Subject
      participation will culminate with sequential subcutaneous administration of a single dose of
      control vehicle solution (control) followed by the dopamine agonist apomorphine (after
      appropriate pre-medication with the anti-emetic, trimethobenzamide) or two sequential
      injections of vehicle for PET scans with attendant radiolabeled compounds.

      D. Outcome Parameters

      This study has four specific aims. First, regional cerebral blood flow will be quantified in
      response to an acute challenge with apomorphine s.c. and compared between study groups
      (ADHD/non-ADHD). Second, dopamine D(2)-like receptor signal transduction will be evaluated by
      PET in response to an acute challenge with apomorphine s.c. and compared between study groups
      (ADHD/non-ADHD). Third, baseline esterified and unesterified serum fatty acids will be
      compared between patients and control subjects. Lastly, we will examine the acute effect of
      apomorphine in the stimulation of serum growth hormone in all subjects, as confirmatory
      evidence for stimulation of central dopaminergic receptors.
    

Time perspective: Other
Keywords: Phospholipase A2; D2 Receptors; Apomorphine; Trimethobenzamide; Attention Deficit Hyperactivity Disorder; ADHD; Healthy Volunteer; HV