Attention Deficit Hyperactivity Disorder (ADHD) is the most common behavioral disorder in childhood, affecting 3-5% of children between the ages of 7 and 17. Family studies suggest that there is a genetic component to ADHD. Scientists believe that it is a complex disorder in which two or more genes may be involved.

Potentially eligible families will be asked to give written consent to participate and will be asked to complete questionnaires for each member in the family. In addition, an interview will be administered to the parent of minors enrolled in the study to determine their eligibility for being in the study. This screening tool is computerized and will take approximately 45 minutes to administer per child.

Once screenings are completed, a blood collection kit will be sent to the family to take to their local medical care provider, have blood samples drawn and sent to NIH. There is no cost to the family to participate. We would like to enroll entire families, with both parents and all children.

A study of the hypothesis that Attention Deficit Hyperactivity Disorder (ADHD) is a genetically influenced brain disorder has been undertaken using a two armed approach: 1) a large, extended pedigree study done in Columbia, South America in a population isolate called the Paisa; and 2) a U.S. based study with at least one affected child and at least one sibling (either affected or unaffected), and their parents. Following careful phenotyping, DNA from blood samples from these two groups will be analyzed through a genome-wide scan for linkage and positional candidate approach to search for genes associated with ADHD. The prefrontal cortex is known to play a very important role in the processing of emotions and impulsivity. Measurement of brain metabolites in this region may be very useful in phenotyping ADHD. Thus, in the Columbian population, in a subset of already recruited individuals, phenotyping will include proton magnetic resonance spectroscopy (H MRS) to detect biochemical phenotypes which may be correlated with genetic markers for ADHD.

• Anderson JC, Williams S, McGee R, Silva PA. DSM-III disorders in preadolescent children. Prevalence in a large sample from the general population. Arch Gen Psychiatry. 1987 Jan;44(1):69-76.
• Biederman J, Faraone S, Milberger S, Guite J, Mick E, Chen L, Mennin D, Marrs A, Ouellette C, Moore P, Spencer T, Norman D, Wilens T, Kraus I, Perrin J. A prospective 4-year follow-up study of attention-deficit hyperactivity and related disorders. Arch Gen Psychiatry. 1996 May;53(5):437-46.
• Faraone SV, Biederman J, Chen WJ, Milberger S, Warburton R, Tsuang MT. Genetic heterogeneity in attention-deficit hyperactivity disorder (ADHD): gender, psychiatric comorbidity, and maternal ADHD. J Abnorm Psychol. 1995 May;104(2):334-45.

• INCLUSION CRITERIA:

For both the U.S. and the Columbian Studies, we plan to obtain blood samples from subjects meeting the following criteria:

Children , ages 7-17, affected with ADHD with siblings who are either affected or unaffected, and their parents. (in the Columbian Study, we will also gather information and blood samples from extended families).

Adult participants 18 years or older selected for MRS from the Paisa population will be included if they:

1. share the haplotype that is in linkage disequilibrium at chormosome 11 p
2. do not have devices such as pace makers, cochlear implants, metal clips in the brain, etc that would preclude them from undergoing magnetic resonance technology
3. are not pregnant (pregnancy test will be administered) or breastfeeding

4. do not have a mental condition such as claustrophobia which would make magnetic resonance tehcnology unacceptable to them.

   EXCLUSION CRITERIA:

   Exclude the following (if the condition could cause false positive ADHD):

   • Prematurity
   • Neurological conditions
   • Cardiac surgery
   • Prenatal drug exposure
   • Hydrocephaly
   • Mental Retardation (IQ of less than 80)
   • Known genetic syndromes
   • Known CNS disorders
   • Known lead toxicity
   • Tourette Disorder
   • Obsessive-Compulsive Disorder
   • Major Depression on both proband and affected sibling
   • Pervasive Developmental Disorder
   • Age under 7 years old
   • Autism
   • Other Psychoses
   • Post Traumatic Stress Disorder
   • Language Disorder (if known)
   • Severe Sensory Impairment (visual and hearing).

   No bilineal families for statistical reasons are to be included, i.e. families in which both father and mother are known to be affected with ADHD. In order to involve either parent, there must be affected siblings.

   Include, but note:

   • Oppositional Defiant Disorder
   • Conduct Disorder
   • Tic Disorder
   • Obsessive/Compulsive Symptoms
   • Anxiety/Phobias
   • Learning Disabilities.