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ADHD in a SNAP: The SNAP gene in attention deficit hyperactivity

Attention Deficit Hyperactivity Disorder (ADHD) is a neuropsychiatric condition characterized by hyperactive-impulsive behavior and persistent inattention. Individuals with this condition experience social and academic dysfunction. It is postulated that a developmental failure in the brain mechanism underlies self-control and inhibition in ADHD. ADHD affects approximately 3 to 6% of children from different geographical regions worldwide. Boys are affected more frequently than girls, with the ratio ranging from 3:1 to 9:1. Family studies have indicated a strong genetic component in susceptibility to ADHD. An approximate five to six fold increase in the frequency of ADHD among first-degree relatives when compared with the general population was observed. A number of twin studies have estimated the heritability of ADHD to range from 39% to 91% for various symptoms of the disorder.

Synaptosomal-associated protein 25 (SNAP-25) is a protein which is expressed highly and specifically in the nerve cells. The gene encodes a protein essential for synaptic vesicle fusion and neurotransmitter release. Animal model studies have shown that the coloboma mouse mutant has a hyperactive phenotype similar to that of ADHD. This model was shown to be the result of a deletion of the SNAP-25 gene. This deletion may have a direct consequence on the neurotransmitter release that has been implicated in the susceptibility to ADHD. DNA variations within or closely mapped to the SNAP-25 gene may alter the level of expression of the gene and hence may have an effect on the neurotransmitter release. We analysed 93 ADHD trios (child, mother and father) from Ireland and found increased preferential transmission of SNAP-25/DdeI variant to ADHD cases (c2= 6.55, p = 0.01). This provides preliminary evidence for the involvement of SNAP-25 in predisposing to ADHD at least in the Irish population. Replication of these results is required to firmly implicate SNAP-25 as a predisposing factor for A
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Contact: Aimee Midei
molecularpsychiatry@mednet.ucla.edu
310-206-6739
Molecular Psychiatry
23-Sep-2002


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